Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruitment ended
Participants planned
3,471
Countries
13
Sites
114
Respiratory tract infection
The primary objective of this Platform is, for hospitalized patients with acute respiratory tract infection, to evaluate the effect of a range of interventions on a composite of 90-day all-cause mortality and, among survivors, a daily ordinal scale of trajectory of illness and recovery to 28 days.
Key facts
- Sponsor
- Universitair Medisch Centrum Utrecht
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Respiratory Tract Diseases [C08]
- Trial duration
- 19 Feb 2016 → ongoing
- Decision date (initial)
- 2024-04-03
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- European Union Grant
External identifiers
- EU CT number
- 2023-507889-89-00
- EudraCT number
- 2015-002340-14
- WHO UTN
- U1111-1189-1653
- ClinicalTrials.gov
- NCT02735707
- ISRCTN
- ISRCTN67000769
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Safety, Efficacy
The primary objective of this Platform is, for hospitalized patients with acute respiratory tract infection, to evaluate the effect of a range of interventions on a composite of 90-day all-cause mortality and, among survivors, a daily ordinal scale of trajectory of illness and recovery to 28 days.
Secondary objectives 3
- The secondary objectives are to determine the effect of interventions on hospital length of stay (LOS) and 90 day mortality
- As well as other endpoints as indicated for specific domains, and, where feasible or specified in a DSA or RSA
- Survival, health related quality of life (HRQoL), and disability assessed after 180 days.
Conditions and MedDRA coding
Respiratory tract infection
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | HLGT | 10024970 | Respiratory tract infections | 10038738 |
Study design 8 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Influenza Antiviral This domain aims to determine the effectiveness of different antiviral strategies for patients admitted to the hospital with microbiological testing confirmed influenza virus infection , including patients with suspected or proven COVID-19 infection (in moderate or severe state). In this domain, patients are randomised to receive:
- No antiviral agents (no placebo)
- 5 days of oseltamivir
- 10 days of oseltamivir
- Baloxavir marboxil (“baloxavir”) on days 1 and 4
- 5 days of oseltamivir + baloxavir on days 1 and 4
- 10 days of oseltamivir + baloxavir on days 1 and 4
|
Randomised Controlled | None | No antiviral agents (no placebo): Patients allocated to the No antiviral agents intervention should not receive any oseltamivir, baloxavir, or other antiviral agents intended to be active against influenza while the patient remains in hospital, up until study day 28. If oseltamivir or baloxavir have been administered or prescribed prior to randomisation, they should be discontinued immediately. 5 days of oseltamivir: Patients allocated to the 5-day course of oseltamivir are to be prescribed a five-day course commencing immediately after reveal of allocation (to not include a dose administered before randomisation). Dosing is determined by the treating clinician. 10 days of oseltamivir: Patients allocated to the 10-day course of Oseltamivir are to be prescribed a ten-day course commencing immediately after reveal of allocation (to not include a dose administered before randomisation). Dosing is determined by the treating clinician. Baloxavir on days 1 and 4: Patients allocated to receive Baloxavir on days 1 and 4 are to be prescribed Baloxavir, on days 1 and 4 after reveal of allocation. Dosing is weight-dependent and specified in the protocol. 5 days of oseltamivir + baloxavir on days 1 and 4: Patients allocated to receive the 5-day course of oseltamivir + baloxavir on days 1 and 4 are to be prescribed both oseltamivir and baloxavir: Patients are to be prescribed a five-day course of oseltamivir commencing immediately after reveal of allocation (to not include a dose administered before randomisation). Dosing is determined by the treating clinician. AND Baloxavir to be prescribed on days 1 and 4 after reveal of allocation. Dosing is weight-dependent and specified in the protocol. 10 days of oseltamivir + baloxavir on days 1 and 4: Patients allocated to receive the 10-day course of oseltamivir + baloxavir on days 1 and 4 are to be prescribed both oseltamivir and baloxavir: Patients are to be prescribed a ten-day course of oseltamivir commencing immediately after reveal of allocation (to not include a dose administered before randomisation). Dosing is determined by the treating clinician. AND Baloxavir to be prescribed on days 1 and 4 after reveal of allocation. Dosing is weight-dependent and specified in the Domain Specific Appendix (DSA). |
|
| 2 | Corticosteroid This domain aims to determine the effectiveness of different strategies of corticosteroid utilisation in the treatment of patients with community acquired pneumonia (CAP) admitted to intensive care units. In this domain, patients are randomised to receive one of up to four steroid-use strategies depending on availability and acceptability:
- No corticosteroid, including hydrocortisone (no placebo)
- Fixed duration hydrocortisone for 7 days
- Shock-dependent hydrocortisone while the patient is in septic shock
- Fixed duration dexamethasone for 10 days
|
Randomised Controlled | None | No corticosteroid, including hydrocortisone (no placebo): In this intervention, patients are not to receive any systemic corticosteroid (including hydrocortisone or dexamethasone) for this episode of Community-Acquired Pneumonia (CAP) or its direct complications up until study day 28 or hospital discharge, whichever occurs first. Shock-dependent hydrocortisone while the patient is in septic shock: Patients randomised to the shock-dependent hydrocortisone intervention are to receive 50mg IV hydrocortisone every 6 hours while the patient is in septic shock as a result of the patient’s initial episode of CAP, up until study day 28. The intervention is to commence as soon as septic shock is diagnosed, including immediately after randomisation if septic shock has already been diagnosed. For the purposes of this intervention, septic shock is defined as: - Administration of any vasopressor by continuous infusion, AND - The treating clinician believes that the vasopressor requirement is due to the CAP, and not for another reason such as untreated hypovolaemia or solely to offset the effects of other ICU interventions (such as administration of sedation or mechanical ventilation).The exact dose of vasopressor that defines septic shock is not defined by the protocol, but is based on the judgement of the treating clinician. Hydrocortisone administration is to cease when the clinician believes that septic shock has resolved. Hydrocortisone should be ceased prior to ICU discharge. Fixed duration dexamethasone for 10 days: In this intervention, patients are to receive a course of dexamethasone 6mg (IV or enteral) daily for 10 days while in hospital. In pregnancy, dexamethasone should be replaced by oral prednisolone 40mg once daily, or IV hydrocortisone 50mg every 6 hours, for 10 days. Administration is to commence immediately after allocation is revealed at the time of randomisation. It will be considered a protocol deviation if during the 10 day course more than two sequential doses of dexamethasone are missed, or if three or more individual doses are missed. The ten-day course will be administered until at least the end of study day 10, and no longer than the end of study day 11 (i.e. it is intended that 10 doses are administered). For patients discharged from hospital before the end of the ten day course, dexamethasone should be discontinued at hospital discharge. For patients allocated to the fixed duration dexamethasone intervention who later develop septic shock, a decision to cease dexamethasone and commence a course of hydrocortisone will be at the discretion of the treating clinician, and will not be considered a protocol deviation. |
|
| 3 | Antibiotics This domain aims to test the effectiveness of different empiric antibiotic treatments in patients with severe community-acquired pneumonia (CAP) who are admitted to an Intensive Care Unit (ICU), including patients with suspected or proven COVID-19 infection. In this domain patients will be randomized to receive one of up to 4 antibiotic interventions depending on availability and acceptability:
- Ceftriaxone + Macrolide
- Moxifloxacin or Levofloxacin
- Piperacillin-tazobactam + Macrolide
- Amoxicillin-clavulanate + Macrolide
|
Randomised Controlled | None | Ceftriaxone + Macrolide: Patient will be prescribed Ceftriaxone. Treatment should commence as soon as possible. The dose, frequency and duration of this allocated antibiotic therapy is up to the treating clinician. The dose specified in the Domain Specific Appendix (DSA) is a recommended minimum dose. AND Patient will be prescribed a macrolide (IV azithromycin; IV clarithromycin; enteral azithromycin; enteral clarithromycin or roxithromycin; or IV or enteral erythromycin). The dose, route and frequency of the macrolide therapy are up to the treating clinician. The REMAP‐CAP preferred macrolide is Intravenous Azithromycin. Moxifloxacin or Levofloxacin: Patient will be prescribed Moxifloxacin OR Patient will be prescribed Levofloxacin. Treatment should commence as soon as possible. The doses, frequency and duration of the allocated antibiotics therapy are up to the treating clinician. The doses specified in the Domain Specific Appendix (DSA) are recommended minimum doses. Piperacillin-Tazobactam + Macrolide: Patient will be prescribed Piperacillin-tazobactam. Treatment should commence as soon as possible. The dose, frequency and duration of this allocated antibiotic therapy is up to the treating clinician. The dose specified in the Domain Specific Appendix (DSA) is a recommended minimum dose. AND Patient will be prescribed a macrolide (IV azithromycin; IV clarithromycin; enteral azithromycin; enteral clarithromycin or roxithromycin; or IV or enteral erythromycin). The dose, route and frequency of the macrolide therapy are up to the treating clinician. The REMAP‐CAP preferred macrolide is Intravenous Azithromycin. Amoxicillin-Clavulanate + Macrolide: Patient will be prescribed Amoxicillin-clavulanate. Treatment should commence as soon as possible. The dose, frequency and duration of this allocated antibiotic therapy is up to the treating clinician. The dose specified in the Domain Specific Appendix (DSA) is a recommended minimum dose. AND Patient will be prescribed a macrolide (IV azithromycin; IV clarithromycin; enteral azithromycin; enteral clarithromycin or roxithromycin; or IV or enteral erythromycin). The dose, route and frequency of the macrolide therapy are up to the treating clinician. The REMAP‐CAP preferred macrolide is Intravenous Azithromycin. |
|
| 4 | Endothelial Modulation This domain aims to determine the effectiveness of interventions that modulate endothelial function for patients with severe CAP, including proven or suspected COVID-19 or influenza or both. endothelial modulators for patients with severe community-acquired pneumonia, including those with suspected or confirmed COVID-19. In this domain, patients are randomised to one of two interventions:
- No endothelial modulator
- Enteral imatinib
|
Randomised Controlled | None | No endothelial modulator: Patients allocated to the no endothelial modulator therapy intervention must not receive imatinib, or any other tyrosine kinase inhibitor targeting the same pathway as imatinib (e.g. dasatinib, nilotinib) unless for an accepted clinical indication, until the end of study day 14 or until intensive care unit discharge, whichever occurs first. Enteral imatinib: Patients allocated to this intervention will be administered imatinib enterally as a 800mg loading dose (study day 1), followed by 400mg administered once daily (study days 2-14). Enteral imatinib administration is to commence as soon as possible after allocation status is revealed. Enteral imatinib is to be administered for a total of 14 days or until ICU discharge, whichever occurs first. |
|
| 5 | Macrolide Duration This domain aims to determine the effectiveness of standard course versus extended course macrolide treatment in patients with community-acquired pneumonia admitted to intensive care units and allocated to receive a beta-lactam antibiotic intervention in the Antibiotic Domain are randomised to one of two interventions:
- Standard course macrolide discontinued between day 3 and day 5
- Extended course macrolide for 14 days or hospital discharge, whichever occurs first
|
Randomised Controlled | None | Standard course macrolide (for 3 to 5 days): In the standard course intervention, patients will receive 3 to 5 days of macrolide therapy. The dosing of and route of administration of macrolide antibiotics are not specified in the protocol but the following guidance is provided: - Initial IV administration of a macrolide is strongly preferred - The preferred IV macrolide is azithromycin, but IV clarithromycin may be substituted. - The preferred enteral macrolide is azithromycin, but enteral clarithromycin or roxithromycin may be substituted. - Sites where erythromycin is the only available macrolide will not be able to participate in this domain. Recommended minimum doses are specified in the Domain Specific Appendix (DSA). These should be modified in accordance with local guidelines and/or practice. Extended course macrolide (for 14 days): In the extended course therapy intervention, patients will continue to receive the macrolide for 14 days or until discharge from hospital, if hospital discharge occurs before 14 days have elapsed. The dosing of and route of administration of macrolide antibiotics are not specified in the protocol but the following guidance is provided: - Initial IV administration of a macrolide is strongly preferred - The preferred IV macrolide is azithromycin, but IV clarithromycin may be substituted. - The preferred enteral macrolide is azithromycin, but enteral clarithromycin or roxithromycin may be substituted. - Sites where erythromycin is the only available macrolide will not be able to participate in this domain. Recommended minimum doses are specified in the Domain Specific Appendix (DSA). These should be modified in accordance with local guidelines and/or practice. |
|
| 6 | Mechanical Ventilation This domain aims to determine the most effective mechanical ventilation strategies for the treatment of patients with severe CAP and COVID-19 pneumonia who are receiving invasive mechanical ventilation. Patients will be randomized to receive one of the two interventions:
- Protocolized mechanical ventilation
- Clinician-preference mechanical ventilation
|
Randomised Controlled | None | Clinician‐preferred mechanical ventilation strategy: Patients allocated to the clinician-preferred mechanical ventilation strategy intervention will have all ventilatory parameters decided by the treating clinician. Any and all ventilatory parameters, including mode of ventilation, can be adjusted at any time. If the treating clinician would usually apply low tidal volume ventilation this is acceptable. The duration of administration of the allocated intervention is at the discretion of the treating clinician. Adherence to the allocated mechanical ventilation strategy should continue as long as the patient is receiving invasive mechanical ventilation or until the end of study day 28 after randomisation in this domain, whichever occurs first. Protocolized mechanical ventilation strategy: Patients allocated to the protocolised ventilation strategy intervention will have ventilatory parameters determined by the protocolised strategy (High PEEP strategy or Standard PEEP strategy as per study protocol). The duration of administration of the allocated intervention is at the discretion of the treating clinician. Adherence to the allocated mechanical ventilation strategy should continue as long as the patient is receiving invasive mechanical ventilation or until the end of study day 28 after randomisation in this domain, whichever occurs first. |
|
| 7 | Influenza Immune modulation This domain aims to determine the effectiveness of different immune modulating strategies for critically ill patients with microbiological testing-confirmed influenza virus infection. In this domain, patients are randomised to receive one of up to three interventions depending on availability and acceptability:
- No immune modulation (no placebo)
- Tocilizumab
- Baricitinib
|
Randomised Controlled | None | No immune modulation (no placebo): Patients allocated to the No immune modulation intervention should not receive any targeted immune modulation therapy intended to be active against influenza while the patient remains in hospital, until the end of study day 28. Tocilizumab: Patients allocated to the Tocilizumab intervention are to be prescribed a single dose of tocilizumab, administered via an intravenous infusion as soon as possible after reveal of allocation. Dosing of tocilizumab is dependent on age and weight. Baricitinib: Patients allocated to the Baricitinib intervention are to be prescribed a ten-day course commencing as soon as possible after reveal of allocation. Dosing of Baricitinib is based on age and renal function. |
|
| 8 | Immunoglobulin This domain aims to determine the effectiveness of different immunoglobulin strategies for immunosuppressed patients with microbiological testing-confirmed COVID-19 (moderate and severe state). In this domain, patients are randomised to receive one of two interventions:
- No immunoglobulin against COVID-19 (no placebo)
- High titre convalescent plasma
|
Randomised Controlled | None | No immunoglobulin against COVID-19 (no placebo): Patients allocated to the no immunoglobulin intervention must not receive any preparation of polyclonal immunoglobulin intended to neutralize SARS-CoV-2 during the index hospitalisation. Administration of such a preparation is considered a protocol deviation. Administration of a monoclonal antibody preparation is permitted prior to randomisation to this domain. High‐titre convalescent plasma: Patients allocated to the convalescent plasma intervention should receive two adult units of ABO compatible convalescent plasma (total volume 550ml ± 150ml) within 48 hours of randomisation. Convalescent plasma must be high titre plasma derived from whole blood or via apheresis from vaccinated donors who have also had a natural infection. |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Hospitalized patient
- Acute respiratory tract infection
- Aged 28 days or older
- Domain-specific eligibility criteria are met
- The patient is eligible for at least two interventions within a domain
Exclusion criteria 3
- Death is deemed to be imminent and inevitable during the next 24 hours AND one or more of the patient, substitute decision maker or attending physician are not committed to full active treatment
- Patient is expected to be discharged from hospital within the next 24 hours
- Previous enrollment in this platform trial within the last 90 days
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- The primary endpoint, named Survival and Recovery Trajectory, will be a composite of 90-day all-cause mortality and, among survivors, a daily ordinal scale analyzed as a trajectory of illness and recovery to 28 days.
- This hierarchical ordinal scale is a composite of: • Landmark mortality at Day 90 post-randomization • Among Day-90 survivors, their daily respiratory support level as defined by position on a five-category ordinal scale: • Hospitalized on ECMO or invasive mechanical ventilation. • Hospitalized on non-invasive ventilation or high-flow oxygen. • Hospitalized on low-intensity oxygen. • Hospitalized, no oxygen. • Discharged from index hospitalization
Secondary endpoints 2
- The generic key secondary endpoints for the trial are: • Hospital length-of-stay • Mortality censored at 90 days
- Domain-specific secondary outcomes (during the index hospitalization, censored 90 days after enrolment)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 20
SUB05660MIG · Substance
- Active substance
- Azithromycin
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 500 mg milligram(s)
- Max total dose
- 7 g gram(s)
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB07017MIG · Substance
- Active substance
- Dexamethasone
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS INJECTION
- Max daily dose
- 6 mg milligram(s)
- Max total dose
- 60 mg milligram(s)
- Max treatment duration
- 10 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB07017MIG · Substance
- Active substance
- Dexamethasone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 6 mg milligram(s)
- Max total dose
- 60 mg milligram(s)
- Max treatment duration
- 10 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06605MIG · Substance
- Active substance
- Erythromycin
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 4 g gram(s)
- Max total dose
- 56 g gram(s)
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB03553MIG · Substance
- Active substance
- Oseltamivir
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL USE
- Max daily dose
- 150 mg milligram(s)
- Max total dose
- 1500 mg milligram(s)
- Max treatment duration
- 10 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1130275 · ATC
- Active substance
- Amoxicillin Sodium
- Route of administration
- IV INJECTION, IV INFUSION
- Max daily dose
- 4 g gram(s)
- Max total dose
- 56 g gram(s)
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01CR02 — AMOXICILLIN AND BETA-LACTAMASE INHIBITOR
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06641MIG · Substance
- Active substance
- Clarithromycin
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 1 g gram(s)
- Max total dose
- 14 g gram(s)
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB01944MIG · Substance
- Active substance
- Erythromycin Lactobionate
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INFUSION
- Route of administration
- IV INJECTION, IV INFUSION
- Max daily dose
- 12 g gram(s)
- Max total dose
- 168 g gram(s)
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB25387 · Substance
- Active substance
- Imatinib
- Pharmaceutical form
- FILM COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 800 mg milligram(s)
- Max total dose
- 6 g gram(s)
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB180983 · Substance
- Active substance
- Baricitinib
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 4 mg milligram(s)
- Max total dose
- 40 mg milligram(s)
- Max treatment duration
- 10 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB10400MIG · Substance
- Active substance
- Roxithromycin
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 300 mg milligram(s)
- Max total dose
- 4.2 g gram(s)
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB20313 · Substance
- Active substance
- Tocilizumab
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 8 mg milligram(s)
- Max total dose
- 800 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB08065MIG · Substance
- Active substance
- Hydrocortisone
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION/INFUSION
- Route of administration
- IV INJECTION, IV INFUSION
- Max daily dose
- 200 mg milligram(s)
- Max total dose
- 1400 mg milligram(s)
- Max treatment duration
- 7 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1153878 · ATC
- Active substance
- Piperacillin Sodium
- Route of administration
- IV INFUSION
- Max daily dose
- 16 g gram(s)
- Max total dose
- 224 g gram(s)
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01CR05 — PIPERACILLIN AND BETA-LACTAMASE INHIBITOR
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB190816 · Substance
- Active substance
- Baloxavir Marboxil
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 80 mg milligram(s)
- Max total dose
- 160 mg milligram(s)
- Max treatment duration
- 2 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Clinical supply tablets are without embossment while Marketing Authorized Product is debossed with “772” on one side and “20” on the other side.
SUB05660MIG · Substance
- Active substance
- Azithromycin
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 500 mg milligram(s)
- Max total dose
- 7 g gram(s)
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB08471MIG · Substance
- Active substance
- Levofloxacin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 1 g gram(s)
- Max total dose
- 14 g gram(s)
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB09086MIG · Substance
- Active substance
- Moxifloxacin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 400 mg milligram(s)
- Max total dose
- 5.6 g gram(s)
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB07431MIG · Substance
- Active substance
- Ceftriaxone
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION/INFUSION
- Route of administration
- IV INJECTION, IV INFUSION
- Max daily dose
- 4 g gram(s)
- Max total dose
- 56 g gram(s)
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06641MIG · Substance
- Active substance
- Clarithromycin
- Pharmaceutical form
- POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 1 g gram(s)
- Max total dose
- 14 g gram(s)
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Universitair Medisch Centrum Utrecht
- Sponsor organisation
- Universitair Medisch Centrum Utrecht
- Address
- Heidelberglaan 100
- City
- Utrecht
- Postcode
- 3584 CX
- Country
- Netherlands
Scientific contact point
- Organisation
- Universitair Medisch Centrum Utrecht
- Contact name
- Lennie Derde
Public contact point
- Organisation
- Universitair Medisch Centrum Utrecht
- Contact name
- Lennie Derde
Third parties 20
| Organisation | City, country | Duties |
|---|---|---|
| Monash University ORG-100042821
|
Clayton, Australia | Code 5 |
| B. Synovia Ltd. ORL-000009828
|
Zagreb, Croatia | On site monitoring, Code 12 |
| Universitair Medisch Centrum Utrecht ORG-100008351
|
Utrecht, Netherlands | Code 14 |
| Mediolanum Cardio Research S.r.l. ORG-100010094
|
Milan, Italy | On site monitoring, Code 12 |
| Sanquin Blood Supply Foundation ORG-100013180
|
Amsterdam, Netherlands | Other |
| Radboud Translational Medicine B.V. ORG-100013306
|
Nijmegen, Netherlands | Laboratory analysis |
| Tartu University Hospital ORG-100012694
|
Tartu Linn, Estonia | On site monitoring, Code 12 |
| Berry Consultants, LCC. ORL-000009833
|
Austin, United States | Code 10 |
| Hungarotrial Zrt. ORQ-110170489
|
Budapest, Hungary | On site monitoring, Code 12 |
| Etablissement Français du Sang ORL-000009830
|
Saint-Denis, France | Other |
| Universidade Nova de Lisboa ORL-000009829
|
Lisboa, Portugal | On site monitoring, Code 12 |
| Roche Products Limited ORG-100003787
|
Welwyn Garden City, United Kingdom | Code 14, Other |
| Fundacion Para La Investigacion Biomedica De Cordoba ORG-100023743
|
Cordoba, Spain | On site monitoring, Code 12 |
| Assistance Publique Hopitaux De Paris ORG-100004082
|
Paris Cedex 12, France | On site monitoring, Code 12, Code 5 |
| Institut National de la Santé et de la Recherche Médicale ORL-000010727
|
Strasbourg CEDEX, France | Code 2 |
| University College Dublin ORG-100009236
|
Dublin 4, Ireland | On site monitoring, Code 12, Code 5 |
| Universitaetsklinikum Jena KöR ORG-100022519
|
Jena, Germany | On site monitoring, Code 12, Code 5 |
| Stichting European Clinical Research Alliance on Infectious Diseases ORG-100048262
|
Utrecht, Netherlands | On site monitoring, Code 12, Code 2, Code 5, Code 8, Code 9 |
| Intensive Care National Audit and Research Centre ORL-000009832
|
London, United Kingdom | On site monitoring, Code 12, Other, Code 5 |
| University Hospital Zurich ORG-100029204
|
Zurich, Switzerland | Code 12 |
Locations
13 EU/EEA countries · 114 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ongoing, recruiting | 200 | 6 |
| Croatia | Ongoing, recruitment ended | 50 | 3 |
| Czechia | Ongoing, recruitment ended | 50 | 2 |
| Estonia | Ongoing, recruitment ended | 50 | 1 |
| France | Ongoing, recruiting | 1,011 | 22 |
| Germany | Ongoing, recruitment ended | 100 | 11 |
| Ireland | Ongoing, recruiting | 200 | 7 |
| Italy | Ongoing, recruitment ended | 250 | 10 |
| Netherlands | Ongoing, recruiting | 1,000 | 36 |
| Portugal | Ongoing, recruitment ended | 75 | 2 |
| Romania | Ongoing, recruitment ended | 60 | 1 |
| Slovenia | Ongoing, recruiting | 125 | 2 |
| Spain | Ongoing, recruiting | 300 | 11 |
| Rest of world | — | 0 | — |
Investigational sites
CHU de Liege
ICU, Domaine Universitaire du Sart-Tilman B35, 4000, Liege
Clinique Saint Pierre
ICU, Avenue Reine Fabiola 9, 1340, Ottignies
Azorg
ICU, Moorselbaan 164, 9300, Aalst
CHU Charleroi
ICU, Chaussée de Bruxelles 140, 6042, Charleroi
Universitair Ziekenhuis Gent
ICU, Corneel Heymanslaan 10, 9000, Gent
CHU UCL NAMUR - Mont Godinne
ICU, Avenue G.Thérasse,1, 5530, Yvoir
General County Hospital Pozega
ICU, Osječka 107, 34000, Pozega
University Hospital for Infectious Diseases ‘Dr. Fran Mihaljevic'
ICU, Mirogojska 8, 10000, Zagreb
University Hospital Centre Zagreb
ICU, Ulica Mije Kispatica 12, 10000, Zagreb
Fakultní nemocnice Královské Vinohrady
ICU, Šrobárova 1150/50, 100 34, Prague
Teplice Hospital
ICU, Duchcovská 962/53, 415 29, Teplice
Tartu University Hospital
ICU, A006, L. Puusepa Tn 8, Tartu Linn
Centre hospitalier Melun
Ward (Internal Medicine), 270 Av. Marc Jacquet, 77000, Melun
Hôpital Lariboisiere
Ward (internal medicine), 2 rue Ambroise Paré, Maladies Infectieuses et Tropicales, Paris
Hopital Tenon
ICU, 4 Rue De La Chine, 75970, Paris Cedex 20
CH de Dax
ICU, Yves du Manoir Boulevard, 40100, Dax
Nouvel Hopital Civil Strasbourg
ICU, 1 Place de l'Hopital, 67000, Strasbourg
Hospital Raymond Poincare
Ward (Internal medicine), 104 boulevard Raymond-Poincaré, 92380, Garches
Centre Hospitalier De Dieppe
ICU, 19 Avenue Pasteur, Cs 20219, Dieppe Cedex
Hôpital Saint-Louis
Ward (internal medicine), 1 Av. Claude Vellefaux, 75010, Paris
Centre Hospitalier des Pays de Morlaix
ICU, ZA Ar Brug, Saint Martin des Champs, Pays de Morlaix
Centre hospitalier de Lens
ICU, 99 Bassée road, 62300, Lens
CHD Vendee
ICU, Les Oudairies, 85925, La Roche sur Yon
Centre Hospitalier Le Mans
ICU, 194 Avenue Rubillard, 72037, Le Mans Cedex 9
Beauvais General Hospital
ICU, 40 Léon Blum Avenue, 60000, Beauvais
Centre Hospitalier Universitaire De Rennes
Ward (internal medicine), 2 Rue Henri Le Guilloux, 35000, Rennes
Hôpital de la Pitié Salpêtrière
Ward (Internal Medicine), 47-83 Bd de l'Hôpital, 75013, Paris
Centre Hospitalier Layne - Mont-de-Marsan
ICU, Pierre de Coubertin Avenue, 40000, Mont de Marsan
CHU Dupuytren
ICU, 2, avenue Martin Luther King, Limoges
Hospital Raymond Poincare
ICU, 104 boulevard Raymond-Poincaré, 92380, Garches
CHU Dijon Bourgogne Hôpital François Mitterand
ICU, 14 rue Gaffarel, 21079, Dijon
CHRU Tours Hopital Bretonneau
ICU, 2 Tonnelle boulevard, 37000, Tours
Centre Hospitalier Universitaire De Nantes
Ward (internal medicine), 1 Place Alexis Ricordeau, 44000, Nantes
Ambroise Pare Hospital
ICU, 3 Villa Alexandrine, 92100, Paris
Universitätsklinikum Jena
ICU, Am Klinikum 1, 07747, Jena
Universitätsklinikum Hamburg-Eppendorf
ICU, Martinistraße 52, 20246, Hamburg
Charité - Universitätsmedizin Berlin
ICU, Augustenburger Platz 1, 13353, Berlin
Universitatsklinikum Leipzig
ICU, Liebigstraße 20, 04103, Leipzig
Campus Charité Mitte
ICU, Charitéplatz 1, 10117, Berlin
Universitätsklinikum Münster
ICU, Albert-Schweitzer-Campus 1, A1, Münster
Universitatsklinikum Leipzig
ICU, Liebigstraße 20, 04103, Leipzig
Universitätsklinikum des Saarlandes
ICU, Klinik für Innere Medizin III Kirrberger Str.100 Homburg/Saar, 66421, Homburg
Klinikum rechts der Isar der TU München
ICU, Ismaningerstr. 22, 81675, München
Universitätsklinikum Würzburg
ICU, Oberdürrbacher Straße 6, 97080, Würzburg
Charité Campus Benjamin Franklin
ICU, Hindenburgdamm 30, 10117, Berlin
University Hospital Waterford
ICU, Dunmore Road, X91 ER8E, Waterford
Beaumont Hospital
ICU, Beaumont Road, Beaumont, Dublin 9
St. Vincent's University Hospital
ICU, 196 Merrion Rd, Elm Park, Dublin
Wexford General Hospital
ICU, Newtown Rd, Carricklawn, Wexford
Tallaght University Hospital
ICU, Tallaght, D24 NR0A, Dublin 24
Cork University Hospital
ICU, Wilton, T12 DC4A, Cork
Galway University Hospital
ICU, Newcastle Road, H91 YR71, Galway
Ospedale Maggiore (Policlinico di Milano Ospedale Maggiore | Fondazione IRCCS Ca' Granda)
Ward (Internal Medicine), Via Francesco Sforza 35, 20122, Milan
Azienda Ospedaliera Spedali Civili di Brescia
ICU, Piazzale Spedali Civili, 25123, Brescia
Arcispedale S. Maria Nuova in Reggio Emilia
ICU, Viale Risorgimento 80, 42123, Reggio Emilia
University Hospital Policlinico Paolo Giaccone
ICU, Via del vespro 129, 90127, Palermo
Humanitas Research Hospital
Ward (Internal Medicine), Via Alessandro Manzoni 56, 20089, Rozzano
Ospedale Infermi di Rimini
ICU, Ospedale Infermi Viale Settembrini 2, 47900, Rimini
IRCCS San Raffaele Scientific Institute
ICU, Via Olgettina 60, 20132, Milan
University Hospital of Modena
ICU, via del Pozzo 71, 41125, Modena
ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione)
ICU, Via Tricomi 5, 90127, Palermo
Humanitas Research Hospital
ICU, Via Alessandro Manzoni 56, 20089, Rozzano
Laurentius Ziekenhuis Roermond
ICU, Monseigneur Driessenstraat 6, 6043 CV, Roermond
Maasstad Ziekenhuis Stichting
ICU, Maasstadweg 21, 3079 DZ, Rotterdam
Dijklander Ziekenhuis
ICU, Maelsonstraat 3, 1624 NP, Hoorn Nh
Amsterdam UMC Stichting
ICU, Meibergdreef 9, 1105 AZ, Amsterdam
Universitair Medisch Centrum Utrecht
ICU, Heidelberglaan 100, 3584 CX, Utrecht
Deventer Ziekenhuis
ICU, Nico Bolkesteinlaan 75, 7416 SE, Deventer
Zuyderland Medisch Centrum Stichting
ICU, Henri Dunantstraat 5, 6419 PC, Heerlen
Canisius Wilhelmina Hospital
ICU, Weg Door Jonkerbos 100, 6532 SZ, Nijmegen
Jeroen Bosch Ziekenhuis
ICU, Henri Dunantstraat 1, 5223 GZ, 's-Hertogenbosch
Bernhoven B.V.
ICU, Nistelrodeseweg 10, 5406 PT, Uden
Medisch Spectrum Twente
ICU, Koningsplein 1, 7512 KZ, Enschede
Rijnstate Ziekenhuis Stichting
Ward (Internal Medicine), Wagnerlaan 55, 6815 AD, Arnhem
Haga Hospital
ICU, Els Borst-Eilersplein 275, 2545 AA, 's-Gravenhage
Radboud universitair medisch centrum / RADBOUDUMC
ICU, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
ICU, Dr. Molewaterplein 60, 3015 GJ, Rotterdam
Radboud universitair medisch centrum / RADBOUDUMC
Ward (internal medicine), Geert Grooteplein Zuid 10, 6525 GA, Nijmegen
Ziekenhuis Gelderse Vallei Stichting
ICU, Willy Brandtlaan 10, 6716 RP, Ede Gld
Maxima Medisch Centrum
ICU, Ds Theodor Fliednerstraat 1, 5631 BM, Eindhoven
Diakonessenhuis Stichting
ICU, Bosboomstraat 1, 3582 KE, Utrecht
Stichting Martini Ziekenhuis
ICU, Van Swietenplein 1, 9728 NT, Groningen
Noordwest Ziekenhuisgroep Stichting
Ward (Internal Medicine), Wilhelminalaan 12, 1815 JD, Alkmaar
Meander Medisch Centrum
ICU, Maatweg 3, 3813 TZ, Amersfoort
Ziekenhuisgroep Twente Stichting
ICU, Zilvermeeuw 1, 7609 PP, Almelo
Universitair Medisch Centrum Groningen
ICU, Hanzeplein 1, 9713 GZ, Groningen
Leids Universitair Medisch Centrum (LUMC)
ICU, Albinusdreef 2, 2333 ZA, Leiden
Amphia Hospital
ICU, Molengracht 21, 4818 CK, Breda
Frisius MC
ICU, Henri Dunantweg 2, 8934 AD, Leeuwarden
Frisius MC
ICU, Thialfweg 44, 8441 PW, Heerenveen
Flevoziekenhuis Stichting
ICU, Hospitaalweg 1, 1315 RA, Almere
IJsselland Ziekenhuis
ICU, Prins Constantijnweg 2, 2906 ZC, Capelle Aan Den Ijssel
Franciscus Gasthuis en Vlietland
ICU, Kleiweg 500, 3118 JH, Rotterdam
OLVG Amsterdam
ICU, Oosterpark 9, 1091 AC, Amsterdam
Slingeland Ziekenhuis
ICU, Kruisbergseweg 25, 7009 BL, Doetinchem
Ikazia Ziekenhuis
ICU, Montessoriweg 1, 3083 AN, Rotterdam
Sint Antonius Ziekenhuis Stichting
ICU, Koekoekslaan 1, 3435 CM, Nieuwegein
Frisius MC
Ward (Internal Medicine), Henri Dunantweg 2, 8934 AD, Leeuwarden
Centro Hospitalar de Lisboa Ocidental
ICU, Estrada do Forte, 1449-005, Lisbon
Centro Hospitalar do Medio Tejo
ICU, Largo Engº Bioucas, 2200-202, Abrantes
Infectious and Tropical Diseases Hospital Dr. Victor Babes
ICU, Şos. Mihai Bravu nr. 281, sector 3, Bucarest
University Clinic Golnik
ICU, Golnik 36, 4204, Golnik
University Medical Centre Maribor
ICU, Ljubljanska ulica 5, 2000, Maribor
Hospital de Tortosa Verge de la Cinta
ICU, Carrer de les Esplanetes 14, 43500, Tortosa
Hospital Universitario de Ourense
ICU, Calle Ramon Puga Noguerol, 54, Ourense
Ramon y Cajal University Hospital
ICU, M-607, 9, Madrid
Hospital la Fe
ICU, Avinguda de Fernando Abril Martorell, 106, València
Hospital Universitario de Jerez
ICU, National IV road, 11407, Cádiz
Hospital De Tortosa Verge De La Cinta
Ward (Internal Medicine), Calle De Les Esplanetes 44, 43500, Tortosa
Dr. Peset University Hospital
ICU, Avda gaspar Aguilar, 90, Valencia
Hospital Regional Universitario de Málaga
ICU, Avenida Carlos Haya, s/n, Málaga
Hospital Universitario Reina Sofia
ICU, Avda. Menéndez Pidal s/n, 14004, Córdoba
University Hospital Marqués de Valdecilla
ICU, Av. de Valdecilla, s/n, Santander
Hospital del Mar
ICU, Passeig Maritim 25-29, 08003, Barcelona
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Belgium | 2019-11-07 | 2019-11-07 | |||
| Croatia | 2020-01-08 | 2020-01-08 | 2025-04-01 | ||
| Czechia | 2022-12-05 | 2023-01-06 | 2025-04-01 | ||
| Estonia | 2021-05-27 | 2021-05-27 | 2024-03-08 | ||
| France | 2020-04-10 | 2020-04-16 | |||
| Germany | 2019-10-25 | 2019-10-25 | 2024-03-08 | ||
| Ireland | 2018-05-02 | 2018-05-02 | |||
| Italy | 2021-02-26 | 2021-02-26 | 2025-05-30 | ||
| Netherlands | 2016-02-19 | 2016-04-11 | |||
| Portugal | 2018-12-06 | 2018-12-06 | 2025-04-01 | ||
| Romania | 2019-11-05 | 2019-11-05 | 2024-03-08 | ||
| Slovenia | 2021-11-25 | 2021-11-25 | |||
| Spain | 2018-10-05 | 2018-10-05 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Serious breaches 1 · Art. 52 CTR
Serious breach SB-31860
- Sponsor became aware
- 2024-06-20
- Date of breach
- 2019-01-02
- Submission date
- 2024-08-22
- Member states concerned
- Belgium, Netherlands, Czechia, Estonia, France, Germany, Ireland, Italy, Portugal, Romania, Slovenia, Spain, Croatia
- Categories
- Regulation
- Areas impacted
- Subject rights
- Benefit-risk balance changed
- No
- Description
- The REMAP-CAP trial recruits patients in the ICU who are often incapacitated, hence unable to provide written informed consent prior to trial inclusion. In these cases, consent by a LAR (Legally Authorized Representative) and/or delayed consent are options according to the trial protocol, to the extent this is allowed by country regulations.
At the site in Portugal, 20 incapacitated patients who could not provide written consent for themselves were included in the trial between 02-Jan-2019 and 24-Jan-2024. In these cases, a close relative/family member has provided prospective written informed consent on the patients’ behalf. The consent procedure is described in the protocol documents and was approved by the CEIC in Portugal on 06-11-2018. The eCRF and Monitoring Visit reports show no record of patient (re)consent from these 20 patients. It is possible that reconsent has been obtained but not yet documented in the eCRF, or attempts have been made to obtain reconsent, but were unsuccessful.
During the monitoring visit on 22-Apr-2024, the local CRA observed that per Portugese legislation, the trial consent procedure was potentially not appropriate. - Sponsor actions
- The CEIC was contacted on 02-May-2024 to request clarification.
At the same time, we paused active recruitment by LAR at the site while awaiting the outcome from the CEIC.
On 20-Jun-2024 the CEIC formally responded that:
“… CEIC considers that the exemption of formal Informed Consent can be accepted with absolute exclusivity, given the methodological circumstances of the trial and admit a relevant interest in Public Health. However, CEIC cannot exempt the trial the informed consent given by the patient for the collection of data. The data that have been collected and the data to be collected in the future, should be confirmed as soon as clinical conditions exist to perform it autonomously. This confirmation of the willingness to collect data can only be performed by the patient himself if he already has the conditions that enable the autonomous decision or in case of continuing with impediment, by the respective health care proxy. The substitution of this autonomy by other figures, other than the health care proxy, regardless of the relationship, is not acceptable. The submitted sheet should be transformed into summary information for the participant and enable it to be made available to the participant, which should include an option of accepting or not dichotomically that the data can be used for the study”.
We have understood that the term “health care proxy” here refers to a court-appointed legal representative, and not a relative of the patient who is not court-appointed.
For some patients at this site, confirmation of agreement to use study data was not sought from the patient themselves or a court-appointed legal representative, as signed informed consent was already present.
This may be seen as a Serious Breach and therefore reported in CTIS as such.
| Organisation | City | Country | Type |
|---|---|---|---|
| Centro Hospitalar Do Medio Tejo E.P.E. | Torres Novas | Portugal | Clinical facility BE/BA |
Unexpected events 1 · Art. 53 CTR
Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.
Unexpected event UE-127683
- Event date
- 2026-03-11
- Date aware
- 2026-03-11
- Submission date
- 2026-04-21
- Member states affected
- Belgium, Netherlands, Czechia, Estonia, France, Germany, Ireland, Italy, Portugal, Romania, Slovenia, Spain, Croatia
- Event description
- We would like to inform you about the recent recommendation that we have received from our independent DSMB: to close recruitment to the oseltamivir interventions (5 and 10 days) of the REMAP-CAP antiviral domain as they have been reported as inferior in critically ill adult patients.
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 191 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_ Master protocol 2023-507889-89-00 Pandemic Appendix redacted | 2 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 Antibiotic Deviations Annex_TC | 2 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 Antibiotics Deviations Annex | 2 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 Biological Sampling Appendix redacted | 1 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 Core Protocol redacted | 4 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 Core Protocol_SoC | 4 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 Core Protocol_TC redacted | 4 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 Corticosteroid Deviations Annex | 2 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 Corticosteroid Deviations Annex_TC | 2 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 COVID-19 Immunoglobulin Therapy Deviations Annex | 1 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Antibiotic Domain redacted | 4 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Antibiotic Domain_SoC | 4 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Antibiotic Domain_TC redacted | 4 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Corticosteroid Domain redacted | 6 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Corticosteroid Domain_SoC | 6 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Corticosteroid Domain_TC from V3 redacted | 6 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Corticosteroid Domain_TC from V3.2 redacted | 6 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Corticosteroid Domain_TC redacted | 6 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA COVID-19 Immunoglobulin Therapy Domain redacted | 4 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA COVID-19 Immunoglobulin Therapy Domain_SoC | 4 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA COVID-19 Immunoglobulin Therapy Domain_TC redacted | 4 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Endothelial Modulation Domain redacted | 2 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Endothelial Modulation Domain_SoC | 2 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Endothelial Modulation Domain_TC redacted | 2 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Influenza Antiviral Domain redacted | 3 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Influenza Antiviral Domain_SoC | 3 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Influenza Antiviral Domain_TC from V1 redacted | 3 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Influenza Antiviral Domain_TC from V2.1 redacted | 3 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Influenza Antiviral Domain_TC redacted | 3 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Influenza Immune Modulation Domain redacted | 2.1 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Influenza Immune Modulation Domain_SoC | 2 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Influenza Immune Modulation Domain_TC redacted | 2.1 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Macrolide Duration Domain redacted | 4 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Macrolide Duration Domain_SoC | 4 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Macrolide Duration Domain_TC redacted | 4 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Mechanical Ventilation Domain redacted | 2 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Mechanical Ventilation Domain_SoC | 2 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 DSA Mechanical Ventilation Domain_TC redacted | 2 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 Endothelial Modulation Deviations Annex | 1 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 EU Region-Specific Appendix redacted | 4 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 EU Region-Specific Appendix_TC from CZ appendix redacted | 4 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 EU Region-Specific Appendix_TC from DE appendix redacted | 4 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 EU Region-Specific Appendix_TC from V3 redacted | 4 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 EU Region-Specific Appendix_TC from V3.5 redacted | 4 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 EU Region-Specific Appendix_TC redacted | 4 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 EU RSA Country Annex BE Redacted | 1 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 EU RSA Country Annex CZ | 1 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 EU RSA Country Annex DE Redacted | 1 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 EU RSA Country Annex EE Redacted | 1 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 EU RSA Country Annex ES Redacted | 1 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 EU RSA Country Annex FR Redacted | 1 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 EU RSA Country Annex HR Redacted | 1 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 EU RSA Country Annex IE Redacted | 1 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 EU RSA Country Annex IT Redacted | 1 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 EU RSA Country Annex NL Redacted | 2.0 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 EU RSA Country Annex NL_TC redacted | 2.0 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 EU RSA Country Annex PT | 2 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 EU RSA Country Annex PT_TC | 2 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 EU RSA Country Annex RO | 1 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 EU RSA Country Annex SI Redacted | 1 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 Immune Modulation Deviations Annex | 1 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 Influenza Antiviral Deviations Annex | 1 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 Macrolide Duration Deviations Annex | 1 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 Patient, Pathogen and Disease Appendix redacted | 1 |
| Protocol (for publication) | D1_Master protocol 2023-507889-89 Registry Appendix redacted | 2 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | NA |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | NA |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | NA |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | NA |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | NA |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | NA |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | NA |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | NA |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | NA |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | NA |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | NA |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | NA |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_fre | NA |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF eng redacted | 16 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF covid redacted | 16 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF COVID-19 LAR redacted | 2.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF COVID-19 redacted | 2.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Data Processing Consent | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Data Processing Consent_TC | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF dut redacted | 17 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF dut_TC redacted | 17 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF est redacted | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF follow up patient redacted | 7.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF follow up patient_TC redacted | 7.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF follow up proxy for adult limited capacity redacted | 7.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF follow up proxy for adult limited capacity_TC redacted | 7.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF follow up proxy for incapacitated adult redacted | 7.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF follow up proxy for incapacitated adult_TC redacted | 7.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF follow up proxy patient dies redacted | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF follow up proxy patient dies_TC redacted | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF follow up proxy redacted | 7.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF follow up proxy_TC redacted | 7.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF fre redacted | 17 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF fre_TC redacted | 17 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF general redacted | 7.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF general_TC redacted | 7.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF LAR redacted | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF LAR redacted | 9 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF LAR_TC redacted | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF main version redacted | 9 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF main version_TC redacted | 9 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF moderate redacted | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF non covid redacted | 16 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF proxy adult with limited capacity redacted | 7.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF proxy adult with limited capacity_TC redacted | 7.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF proxy incapacitated adult redacted | 7.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF proxy incapacitated adult_TC redacted | 7.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF proxy redacted | 7.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF proxy_TC redacted | 7.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF redacted | 17 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF redacted | 4 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF redacted | 5 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF redacted | 6 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF redacted | 8 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF redacted | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF redacted | 33 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF redacted | 9 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF retro redacted | 9 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF rus redacted | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF sCAP LAR redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF sCAP redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF severe redacted | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF shortened version continuation redacted | 8 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF shortened version continuation_TC redacted | 8 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF shortened version redacted | 8 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF shortened version_TC redacted | 8 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF slv redacted | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Telephone LAR redacted | 2.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Telephone LAR_TC | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Trial Information redacted | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Trial Information_TC redacted | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Trial Participation Consent | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Trial Participation Consent_TC | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_TC redacted | 17 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_TC redacted | 4 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_TC redacted | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_TC redacted | 33 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Azithromycin powder | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Azithromycin tablet | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Azithromycin tablet_SoC | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Baloxavir | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Baricitinib | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Baricitinib_SoC | 2.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Ceftriaxone | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Clarithromycin powder | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Clarithromycin tablet | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Clavulanic acid | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Dexamethasone Injection | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Dexamethasone injection_SoC | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Dexamethasone Tablet | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Erythromycin lactobionate powder | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Erythromycin powder_SoC | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Erythromycin tablet | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Erythromycin tablet_SoC | 2.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Hydrocortisone | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Hydrocortisone_SoC | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Imatinib | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Levofloxacin | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Moxifloxacin | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Oseltamivir | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Piperacillin sodium tazobactam sodium powder | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Roxithromycin | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Tocilizumab | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Tocilizumab_SoC | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS cze 2023-507889-89 | 16.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS cze 2023-507889-89_TC | 16.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS dut 2023-507889-89 | 17 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS dut 2023-507889-89_TC | 17 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS eng 2023-507889-89 | 16.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS eng 2023-507889-89_TC | 16.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS fre 2023-507889-89 | V16.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS fre 2023-507889-89_TC | 16.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS ger 2023-507889-89 | 16 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS ger 2023-507889-89_TC | 16 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS hrv 2023-507889-89 | 16.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS hrv 2023-507889-89_TC | 16.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS ita 2023-507889-89 | 16.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS ita 2023-507889-89_TC | 16.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS por 2023-507889-89 | 16.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS por 2023-507889-89_TC | 16.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS rum 2023-507889-89 | 16.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS rum 2023-507889-89_TC | 16.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS slv 2023-507889-89 | 16.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS slv 2023-507889-89_TC | 16.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS spa 2023-507889-89 | 16.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis MS spa 2023-507889-89_TC | 16.0 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-02-09 | Netherlands | Acceptable 2024-03-20
|
2024-03-20 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-11-08 | Netherlands | Acceptable with conditions 2025-03-03
|
2025-03-03 |
| 3 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-06-20 | Netherlands | Acceptable 2025-09-26
|
2025-09-26 |
| 4 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-11-06 | Netherlands | Acceptable | 2025-11-14 |