Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Authorised, recruitment pending
Participants planned
600
Countries
1
Sites
25
antibiotic therapy in Sepsis
To compare the 30-day mortality of patients with hospital-acquired sepsis in the ICU according to the mode of administration of the pivotal βL antibiotic (CID group vs. IID group).
Key facts
- Sponsor
- Assistance Publique Hopitaux De Paris
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Bacterial Infections and Mycoses [C01]
- Decision date (initial)
- 2024-11-26
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-516849-39-01
- EudraCT number
- 2019-002327-15
- ClinicalTrials.gov
- NCT05681442
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacodynamic, Therapy, Pharmacokinetic
To compare the 30-day mortality of patients with hospital-acquired sepsis in the ICU according to the mode of administration of the pivotal βL antibiotic (CID group vs. IID group).
Secondary objectives 4
- 1. 30-day mortality in patients (i) with proven Gram-negative infection (GNI), (ii) with proven non-fermentative GNI, (iii) with proven GNI for which the minimum inhibitory concentration (MIC) of the βL used were higher to the breakpoints according to the European committee on Antimicrobial Susceptibility Testing (EUCAST). 2. 30-day mortality in patients that received non-carbapenem-βL 3. Clinical failure
- 4. PK-PD target attainment at day 1 and day 3 5. Superinfection (primary infection site) or new infection (different infection site) at day 30 due to a GNB resistant to the βL administered at inclusion 6. Microbiological failure among patients with clinical failure.
- 7. New carriage, colonization or infection with one of the following BMR-GNB: at days 3, 7 and 30: - extended spectrum beta-lactamases (ESBL) Enterobacteriaceaeticarcillin-resistant Pseudomonas aeruginosa, Acinetobacter baumannii Stenotrophomonas maltophilia - extended-spectrum β-lactam-producing Entero bacteriaceae - high-concentration cephalosporinase producing AmpC Enterobacteriaceae;
- 8. New carriage, colonization or infection with Pseudomonas aeruginosa not susceptible to the βL administered at days 3, 7 and 30 9. Duration of organ failure between day 1 and day 30 10. Occurrence of adverse events at day 30 11. Length of ICU and hospital stays 12. 180-day mortality
Conditions and MedDRA coding
antibiotic therapy in Sepsis
Regulatory references
- Plan to share IPD
- Yes
- IPD plan description
- All of the individual participant data collected during the trial, subject to compliance to regulations, will be available. Document (Study protocol, statistical analysis plan, informed consent form, clinical study report, analytic code) will be also available. Data will be available immediately following publication ending 2 years after publication, with investigators whose proposed use of the data has been approved by the PI and / or the review commitee if relevant. Proposals should be directed to [email protected]. To gain access, data requestors will need to sign a data access agreement.
| EU CT number | Title | Sponsor |
|---|---|---|
| 2024-516849-39-00 | BICCS - Beta-lactam Intermittent versus Continuous infusion and Combination antibiotic therapy in Sepsis | Assistance Publique Hopitaux De Paris |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- • Adults (≥ 18 years) • Hospital-acquired sepsis (according to sepsis 3.0 definitions) - Patient hospitalized for more than 48 hours OR Patient discharged less than 48 hours ago - AND sepsis diagnosed within the last 24 hours
- •One of the following risk factors for gram negative multidrug resistant pathogens: -Prior intravenous antibiotic use within 7 days prior to sepsis onset with the exception of antibiotic effective only against Gram-positive bacteria, penicillin A and macrolides -Prolonged hospital stay (≥ 15 days of hospitalization) within 3 months prior to sepsis onset Prolonged mechanical ventilation (≥ 5 days on mechanical ventilation) within 3 months prior to sepsis onset-Patients with indwelling devices (dialysis access lines, intravascular lines, urinary catheter, endotracheal or tracheostomy tube, gastrostomy or jejunostomy feeding tube)
- - Patients known to be infected, colonized or carriers of MDR gram negative bacteria within 3 months prior to sepsis onset - Exposure to an antibiotic (amoxicillin-clavulanic acid, C2G, C3G, fluoroquinolones) within 3 months prior to sepsis onset - A trip abroad to known geographical areas at risk (in particular the Indian subcontinent, South-East Asia, the Middle East and North Africa, the Mediterranean Basin) within 3 months prior to sepsis onset - A functional or organic abnormality of the urinary tract in case of urinary tract infection. • Appropriate bacteriological sampling performed before starting antimicrobial therapy • Expected stay in ICU of more than 3 days
Exclusion criteria 4
- • A priori known resistance to all the proposed beta-lactams or to amikacin Need for extrarenal treatment at inclusion according to the criteria of Gaudry et al. • Known hypersensitivity to ceftazidime, piperacillin-tazobactam, cefepime, meropenem, ceftazidime-avibactam, ceftazolane-avibactam or to any of the excipients included in the corresponding pharmaceutical drugs, • Known hypersensitivity to any cephalosporin antibacterial agent, • Know hypersentitivity to any penem antibacterial agent,
- • Severe known hypersensitivity (eg, anaphylactic reaction, severe skin reaction) to any other beta-lactam antibiotic (eg, penicillins or monobactam ) or to any of its excipients. • Known contraindication to the aminoglycoside family including o Hypersensitivity to the active substance, to any aminoglycoside antibacterial agent or to any of the excipients included in the corresponding pharmaceutical drugs, o Cirrhosis of grades B and C according to the Child-Pugh classification. o Myasthenia gravis. o Simultaneous administration of another aminoglycoside o Association with ataluren
- • Non-complicated urinary tract infection (corresponding to a positive ECBU not responsible for sepsis) • Bone marrow transplant or chemotherapy-induced neutropenia • Infections for which long-term antibiotic treatment > 8 days is strongly recommended (i.e., infective endocarditis, osteoarticular infections, anterior mediastinitis after cardiac surgery, hepatic or cerebral abscesses, chronic prostatitis for instance • Presence of antibiotic therapy for the new sepsis (if sepsis acquired in the hospital outside the resuscitation> 2 doses of antibiotics or > 16h for continuous infusion)
- • Limitation of life support (comfort care applied only) at the time of screening • Enrolment to another interventional drug study • Pregnancy or breastfeeding • Subject deprived of freedom, subject under a legal protective measure • Non affiliation to any health insurance system • Refusal to participate to the study (patient or legal representative or family member or close relative if present)
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary endpoint is the mortality rate at day 30 between CID and IID groups.
Secondary endpoints 8
- 1. Mortality rate at day 30 in patients with (i) proven GNI, (ii) proven non-fermentative GNI, (iii) proven GNI for which the MIC of the βL used were higher to the accepted break-points 2. Mortality rate at day 30 in patients that received non-carbapenem-βL
- 3. Clinical failure defined as meeting any of the following: a) Death either while on trial therapy or within 7 days following completion; b) Receipt of rescue therapy for the trial pathogen within 7 days of completion of trial treatment; c) Removal from the trial due to an adverse event considered related to trial treatment; d) Bacteremia more than 5 days after initiation of trial treatment with the same pathogen (if multiple pathogens at least one with the same AST);
- e) Improvement of shock (decrease by more than 50% of the initial norephrine dose or decrease by more at least 2 points of the SOFA score), within 7 days of completion of trial treatment; f) For patients with pneumonia: failure to improve or worsening of oxygenation by the end of trial treatment; g) For patients with intra-abdominal infections and urinary tract infections: need for re-intervention after more than 5 days of effective treatment or need for puncture debridement or sample from th
- 4. PK-PD target attainment rate evaluated as a dichotomous variable o For βL (trough or plateau concentration according to randomization group), at day 1, i.e. 24 hours after the loading dose and at day 3, i.e. 72 hours after the loading dose Target attainment scored “Yes” if measured drug concentration exceeded greater than four times to the causative pathogen MIC as 100% fT > 4*MIC
- o For AG, 30 min after the end of the first infusion dose (CMAX) Target attainment scored “Yes” if measured drug concentration to causative pathogen MIC ratio is greater than 12 as CMAX/MIC > 12
- 5. Percentage of patients with superinfection or new nosocomial infection with GNB resistant to the βL administered at inclusion until day 30 6. Percentage of patients with clinical failure for whom at least one of the microorganism responsible for the infection is still recovered in bacterial culture from the initial infected site at end-of-therapy (EOT) or within 7 days after EOT
- 7. Percentage of patients with new carriage of MDR-GNB until day 30 (taking into account all clinical samples and rectal surveillance swabs performed routinely each week), i.e one of the following ticarcillin-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, or Stenotrophomonas maltophilia; extended-spectrum β-lactam-producing Entero bacteriaceae; high-concentration cephalosporinase producing AmpC Enterobacteriaceae;
- 8. Percentage of patients with new carriage colonization or infection with Pseudomonas aeruginosa not susceptible to the βL administered until day 30 9. Organ failures assessed by AUCSOFA and its organ components measured between day 1 and day 30 10. Percentage of patients with encephalopathy (delay between inclusion and 2 RASS scores = -1 in a row) or renal failure at discharge until day 30 11.Length of ICU and hospital stays until day 30 12.Mortality rate at day 180
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 7
SCP107177473 · ATC
- Active substance
- Cefepime Hydrochloride
- Substance synonyms
- Cefepime dihydrochloride
- Route of administration
- INFUSION
- Max daily dose
- 6 g gram(s)
- Max total dose
- 42 g gram(s)
- Max treatment duration
- 7 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01DE01 — CEFEPIME
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP13237974 · ATC
- Active substance
- Ceftazidime
- Route of administration
- INFUSION
- Max daily dose
- 6 g gram(s)
- Max total dose
- 42 g gram(s)
- Max treatment duration
- 7 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01DD52 — CEFTAZIDIME AND BETA-LACTAMASE INHIBITOR
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1153878 · ATC
- Active substance
- Piperacillin Sodium
- Route of administration
- INFUSION
- Max daily dose
- 16 g gram(s)
- Max total dose
- 112 g gram(s)
- Max treatment duration
- 7 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
SCP101876674 · ATC
- Active substance
- Linezolid
- Route of administration
- INFUSION
- Max daily dose
- 6 g gram(s)
- Max total dose
- 6 g gram(s)
- Max treatment duration
- 7 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01DH02 — MEROPENEM
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP11455928 · ATC
- Active substance
- Tazobactam
- Route of administration
- INFUSION
- Max daily dose
- 6 g gram(s)
- Max total dose
- 42 g gram(s)
- Max treatment duration
- 7 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01DI54 — CEFTOLOZANE AND BETA-LACTAMASE INHIBITOR
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP107188009 · ATC
- Active substance
- Ceftazidime Pentahydrate
- Route of administration
- INFUSION
- Max daily dose
- 12 g gram(s)
- Max total dose
- 84 g gram(s)
- Max treatment duration
- 7 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01DD02 — CEFTAZIDIME
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP108746144 · ATC
- Active substance
- Amikacin Sulfate
- Substance synonyms
- AMIKACIN SULPHATE
- Route of administration
- INJECTION
- Max daily dose
- 30 mg/kg milligram(s)/kilogram
- Max total dose
- 30 mg/kg milligram(s)/kilogram
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01GB06 — AMIKACIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 10
SUB05431MIG · Substance
- Active substance
- Amikacin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INJECTION
- Max daily dose
- 30 mg/kg milligram(s)/kilogram
- Max total dose
- 150 mg/kg milligram(s)/kilogram
- Max treatment duration
- 5 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB08778MIG · Substance
- Active substance
- Meropenem
- Pharmaceutical form
- POWDER FOR INFUSION
- Route of administration
- INJECTION
- Max daily dose
- 6 g gram(s)
- Max total dose
- 42 g gram(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
SUB07390MIG · Substance
- Active substance
- Cefepime
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INJECTION
- Max daily dose
- 6 g gram(s)
- Max total dose
- 6 g gram(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
SUB10849MIG · Substance
- Active substance
- Tazobactam
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INJECTION
- Max daily dose
- 3 g gram(s)
- Max total dose
- 21 g gram(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
SUB167762 · Substance
- Active substance
- Ceftolozane
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INJECTION
- Max daily dose
- 6 g gram(s)
- Max total dose
- 6 g gram(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
SUB07422MIG · Substance
- Active substance
- Ceftazidime
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INJECTION
- Max daily dose
- 12 g gram(s)
- Max total dose
- 84 g gram(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
SUB72111 · Substance
- Active substance
- Avibactam
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INJECTION
- Max daily dose
- 1500 mg milligram(s)
- Max total dose
- 10500 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
SUB07422MIG · Substance
- Active substance
- Ceftazidime
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INJECTION
- Max daily dose
- 6 g gram(s)
- Max total dose
- 6 g gram(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
SUB09867MIG · Substance
- Active substance
- Piperacillin
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INJECTION
- Max daily dose
- 16 g gram(s)
- Max total dose
- 16 g gram(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
SUB10849MIG · Substance
- Active substance
- Tazobactam
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INJECTION
- Max daily dose
- 2 g gram(s)
- Max total dose
- 14 g gram(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
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Assistance Publique Hopitaux De Paris
- Sponsor organisation
- Assistance Publique Hopitaux De Paris
- Address
- Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux
- City
- Paris Cedex 10
- Postcode
- 75475
- Country
- France
Scientific contact point
- Organisation
- Assistance Publique Hopitaux De Paris
- Contact name
- Pr TIMSIT Jean François
Public contact point
- Organisation
- Assistance Publique Hopitaux De Paris
- Contact name
- Pr TIMSIT Jean François
Locations
1 EU/EEA country · 25 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Authorised, recruitment pending | 600 | 25 |
| Rest of world | — | 0 | — |
Investigational sites
Hopital De La Croix-Rousse
Médecine Intensive et Réanimation, 103 Grande Rue De La Croix Rousse, 69317, Lyon Cedex 04
Centre Hospitalier Sud Essonne-Dourdan-Etampes
Réanimation - Surveillance continue, 26 Avenue Charles De Gaulle, 91150, Etampes
Centre Hospitalier De Versailles
Réanimation polyvalente, 177 Rue De Versailles, Le Chesnay, Le Chesnay Rocquencourt
Centre Hospitalier Universitaire De Nice
Médecine intensive – réanimation, 151 Route De Saint Antoine, 06200, Nice
Centre Hospitalier Universitaire Grenoble Alpes
Médecine intensive de réanimation, Boulevard De La Chantourne, Cs 10217, Grenoble Cedex 9
Centre Hospitalier Universitaire De Poitiers
86000, 2 Rue De La Miletrie, 86000, Poitiers
Centre Hospitalier Universitaire D Orleans
Médecine intensive et Réanimation, 14 Avenue De L Hopital, Cs 86709, Orleans Cedex 2
Centre Hospitalier Departemental Vendee
Médecine intensive – réanimation, Boulevard Stephane Moreau, 85925, La Roche Sur Yon Cedex 9
Hospices Civils De Lyon
Médecine intensive – réanimation, 5 Place D Arsonval, 69437, Lyon Cedex 03
Hopital Beaujon
Anesthésie – Réanimation, 100 Boulevard Du General Leclerc, 92110, Clichy
Centre Hospitalier Universitaire De Nice
Médecine intensive et réanimation, 30 Voie Romaine, 06000, Nice
Institut Mutualiste Montsouris
Intensive Care, 42 Boulevard Jourdan, 75014, Paris
Centre Hospitalier D Avignon
Réanimation polyvalente, 305 Rue Raoul Follereau, 84902, Avignon Cedex 9
Centre Hospitalier General De St Denis
Médecine intensive – réanimation CH St Denis - Hôpital Delafontaine, 2 Rue Du Docteur Delafontaine, Bp 279, St Denis Cedex
Centre Hospital Region Metz Thionville
Réanimation polyvalente, 1 Allee Du Chateau, Cs 45001 Ars Laquenexy, Metz Cedex 03
Centre Hospitalier Le Mans
Réanimation Médico Chirurgicale & USC, 194 Avenue Rubillard, 72037, Le Mans Cedex 9
Assistance Publique Hopitaux De Paris
Réanimation médicale et infectieuse, 46 Rue Henri Huchard, 75877, Paris Cedex 18
Centre Hospitalier Victor Dupouy
Réanimation polyvalente, 69 Rue Du Lieutenant Colonel Prudhon, 95107, Argenteuil Cedex
Pellegrin Hospital
Service de Réanimation Médicale, Place Amelie Raba Leon, 33000, Bordeaux
Centre Jean Perrin
Critical Care Medicine, 58 Rue Montalembert, 63011, Clermont Ferrand Cedex1
Les Hopitaux Universitaires De Strasbourg
Médecine intensive – réanimation, 1 Place De L Hopital, 67000, Strasbourg
Centre Hospitalier Universitaire De Montpellier
Anesthésie-Réanimation, 80 Avenue Augustin Fliche, 34295, Montpellier Cedex 5
Centre Hospitalier Universitaire De Montpellier
Médecine intensive – réanimation, 371 Avenue Du Doyen Gaston Giraud, 34090, Montpellier
Assistance Publique Hopitaux De Paris
Réanimation chirurgicale, 46 Rue Henri Huchard, 75877, Paris Cedex 18
Hopital Ambroise Pare
Médecine intensive - réanimation, 9 Avenue Charles De Gaulle, 92100, Boulogne Billancourt
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 27 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_protocol_2024-516849-39-01 | 7.0 |
| Protocol (for publication) | D1_protocol_2024-516849-39-01_Clean | 7 |
| Protocol (for publication) | D1_protocol_2024-516849-39-01_TC | 5 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_LIS and ICF_donnee | 1.0 |
| Subject information and informed consent form (for publication) | L1_LIS and ICF_patient | 1.1 |
| Subject information and informed consent form (for publication) | L1_LIS and ICF_patient poursuite | 1.1 |
| Subject information and informed consent form (for publication) | L1_LIS and ICF_proche | 1.1 |
| Subject information and informed consent form (for publication) | L1_LIS and ICF_proche poursuite | 1.1 |
| Summary of Product Characteristics (SmPC) (for publication) | 2019-002327-15_RCP_AMIKACINE | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | 2019-002327-15_RCP_CEFEPIME | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | 2019-002327-15_RCP_CEFTAZIDIME-AVIBACTAM | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_Preparation manual_CEFEPIME | 4 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_Preparation manual_CEFTAZIDIME | 4 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC _AMIKACINE | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC _MEROPENEM | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_CEFEPIME | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_CEFTAZIDIME | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_CEFTAZIDIME | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_CEFTAZIDIME-AVIBACTAM | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_CEFTOLOZANE-TAZOBACTAM | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_CEFTOLZANE-TAZOBACTAM | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_MEROPENEM | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Piperacilline_tazobactam | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_piperacilline-tazobactam | 2 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_ENG_2024-516849-39-01_Clean | 5 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_FR_2024-516849-39-01_Clean | 5 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-23 | France | Acceptable 2024-11-26
|
2024-11-26 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-03-17 | France | Acceptable 2025-06-04
|
2025-06-05 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-12-02 | France | Acceptable 2025-06-04
|
2025-12-02 |
| 4 | SUBSTANTIAL MODIFICATION | SM-2 | 2026-02-17 | France | Acceptable 2026-03-06
|
2026-03-19 |