Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ended
Participants planned
628
Countries
1
Sites
31
Intensive Care
To demonstrate that cotrimoxazole is non-inferior to best standard of care for the treatment of VAP in ICU.
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], Diseases [C] - Respiratory Tract Diseases [C08]
- Trial duration
- 20 Dec 2023 → 19 Sep 2025
- Decision date (initial)
- 2023-07-20
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- DGOS - Ministry of Health
External identifiers
- EU CT number
- 2023-505108-52-00
- ClinicalTrials.gov
- NCT05696093
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
To demonstrate that cotrimoxazole is non-inferior to best standard of care for the treatment of VAP in ICU.
Secondary objectives 3
- To demonstrate that cotrimoxazole is superior to best standard of care for the treatment of VAP in ICU in terms of: 1) mortality at day 28 2) mortality at day 90 3) mechanical ventilation (MV)-free-days through day 28 4) rate of cure between days 7 and 10 5) VAP recurrence 6) ICU length of stay 7) hospital length of stay 8) overall antibiotic consumption
- To assess the safety of cotrimoxazole compared to best standard of care at day 28 in terms of: 9) allergy to antibiotics
- To assess the ecological impact of the treatment in terms of: 10) acquisition of MDR bacteria in ICU 11) rate of Clostridioides difficile infection
Conditions and MedDRA coding
Intensive Care
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.1 | LLT | 10065153 | Ventilator associated pneumonia | 10021881 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- 1) Adult (age ≥ 18 years)
- 2) Under mechanical ventilation for at least five days
- 3) Microbiologically confirmed VAP preferably on a distal lung sample (bronchoalveolar lavage or protected distal specimen) otherwise endotracheal aspiration
- 4) Enterobacteriaceae susceptible to cotrimoxazole, and for polymicrobial VAP, all bacteria susceptible to
- 5) Treated for at least 24 48 to 72 hours by an appropriate empiric antibiotic therapy (at least one effective antibiotic from the initiation of treatment for this VAP episode) and for polymicrobial VAP, all bacteria susceptible to empiric antibiotic therapy
- Stability of haemodynamic (stability or decrease in catecholamine dose) and respiratory (stability or improvement of FIO2) parameters
Exclusion criteria 12
- 1) Known contra-indication to cotrimoxazole: o allergy, o advanced liver insufficiency, o renal dysfunction with clearance <15 mL/min/1.73 m² without hemodialysis o G6PD deficiency o history of hypersensitivity to one of the components (in particular, hypersensitivity to sulphonamides) o known macrocytic anaemia defined by VGM > 100 fl and haemoglobin < 11 g/dl o treatment with methotrexate
- 10) Subject deprived of freedom, subject under a legal protective measure
- 11) No affiliation to any health insurance system
- 12) Refusal to participate to the study (patient or legal representative or family member or close relative if present)
- 13) Patients previously included in the study
- 2) Infection requiring prolonged antibiotic-therapy (pleural empyema, lung abscess, necrotizing pneumonia, etc…)
- 3) Cystic fibrosis
- 4) Immunosuppression (neutropenia, HIV with CD4 lymphocytes below 200/mm3, immunosuppressive therapy or corticosteroid therapy >0.5 mg/kg/j before ICU admission)
- 5) Cardiac arrest without awakening
- 6) Moribund state (patient likely to die within 24h)
- 8) Enrolment to another interventional study on VAP care/management
- 9) Pregnancy or breastfeeding
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- vital status at day 28
Secondary endpoints 11
- vital status at day 28
- number of mechanical ventilation-free-days from inclusion to day 28 or death.
- Clinical, biological and radiological cure evaluated 7 to 10 days after VAP diagnosis, defined as the combination of resolution of signs and symptoms present at enrolment, biological improvement, and improvement or lack of progression of radiological signs, as adjudicated by an independent committee (PROBE methodology)
- new episode of VAP with the same Enterobacteriaceae
- ICU length of stay
- hospital length of stay
- number of antibiotic free-days from inclusion to day 28 or death.
- safety (rate of allergy due to antimicrobial drug)
- ecological impact: o evolution of rate of MDR bacterial colonization on systematic screening at enrolment until ICU discharge
- diagnostic of Clostridioides difficile infection between inclusion and day 28
- Vital Status at day 90
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SUB13477MIG · Substance
- Active substance
- Co-Trimoxazole
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 5.76 g gram(s)
- Max total dose
- 34.56 g gram(s)
- Max treatment duration
- 6 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 15
SUB05664MIG · Substance
- Active substance
- Aztreonam
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 8 g gram(s)
- Max total dose
- 48 g gram(s)
- Max treatment duration
- 6 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB07470MIG · Substance
- Active substance
- Ciprofloxacin
- Pharmaceutical form
- POWDER FOR INJECTION
- Route of administration
- INTRAVENIOUS INFUSION
- Max daily dose
- 1.2 g gram(s)
- Max total dose
- 7.2 g gram(s)
- Max treatment duration
- 6 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
- POWDER FOR SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 6 g gram(s)
- Max total dose
- 36 g gram(s)
- Max treatment duration
- 6 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB21472 · Substance
- Active substance
- Imipenem Monohydrate
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 4 g gram(s)
- Max total dose
- 24 g gram(s)
- Max treatment duration
- 6 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB09422MIG · Substance
- Active substance
- Ofloxacin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 800 mg milligram(s)
- Max total dose
- 4.8 g gram(s)
- Max treatment duration
- 6 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB25388 · Substance
- Active substance
- Ertapenem
- Pharmaceutical form
- POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 2 g gram(s)
- Max total dose
- 12 g gram(s)
- Max treatment duration
- 6 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB07405MIG · Substance
- Active substance
- Cefotaxime
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 8 g gram(s)
- Max total dose
- 48 g gram(s)
- Max treatment duration
- 6 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 INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 3 g gram(s)
- Max total dose
- 18 g gram(s)
- Max treatment duration
- 6 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
- POWDER FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 16 g gram(s)
- Max total dose
- 96 g gram(s)
- Max treatment duration
- 6 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB00503MIG · Substance
- Active substance
- Amoxicillin Sodium
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION OR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 8.8 g gram(s)
- Max total dose
- 52.8 g gram(s)
- Max treatment duration
- 6 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB05481MIG · Substance
- Active substance
- Amoxicillin
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 8 g gram(s)
- Max total dose
- 48 g gram(s)
- Max treatment duration
- 6 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB10886MIG · Substance
- Active substance
- Temocillin
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 6 g gram(s)
- Max total dose
- 36 g gram(s)
- Max treatment duration
- 6 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 INJECTION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 1 g gram(s)
- Max total dose
- 6 g gram(s)
- Max treatment duration
- 6 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB03840MIG · Substance
- Active substance
- Piperacillin Sodium
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 20 g gram(s)
- Max total dose
- 120 g gram(s)
- Max treatment duration
- 6 Day(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 SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 6 g gram(s)
- Max total dose
- 36 g gram(s)
- Max treatment duration
- 6 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. Damien ROUX
Public contact point
- Organisation
- Assistance Publique Hopitaux De Paris
- Contact name
- Pr. Damien ROUX
Locations
1 EU/EEA country · 31 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ended | 628 | 31 |
| Rest of world | — | 0 | — |
Investigational sites
Centre Hospitalier De Saint-Denis
medecine intensive réanimation, 2 Rue Du Docteur Delafontaine, 93200, Saint-Denis
Centre Hospitalier Universitaire De Bordeaux
Médecine Intensive et Réanimation, Place Amelie Raba Leon, 33000, Bordeaux
Centre Hospitalier Universitaire Grenoble Alpes
Pôle Urgences Medecine Aigue, Boulevard De La Chantourne, Cs 10217 La Tronche, Grenoble Cedex 9
Centre Hospitalier Annecy Genevois
Unité de soin intensif, 1 Avenue De L Hopital, Bp 90074 Epagny Metz Tessy, Pringy Cedex
Centre Hospitalier Universitaire Amiens Picardie
Intensive Care unit, 1 Rond Point Du Professeur Christian Cabrol, 80054, Amiens
CHRU De Nancy
Médecine Intensive et Réanimation, 29 Avenue Du Mal De Lattre De Tassigny, 54000, Nancy
Centre Hospitalier Intercommunal Toulon La Seine-Sur-Mer
Réanimation polyvalente, 54 Rue Henri Sainte Claire Deville, 83100, Toulon
Assistance Publique Hopitaux De Paris
Réanimation médico-chirurgicale, 178 Rue Des Renouillers, 92701, Colombes Cedex
Assistance Publique Hopitaux De Paris
Réanimation médico-chirurgicale, 9 Avenue Charles De Gaulle, 92100, Boulogne-Billancourt
Centre Hospitalier Leon Binet Provins
Réanimation Médicale, Route De Chalautre, 77160, Provins
Centre Hospitalier Universitaire De Lille
Intensive care unit, Rue Emile Laine, 59037, Lille Cedex
University Hospital Of Clermont-Ferrand
Réanimation adulte, 1 Place Lucie Et Raymond Aubrac, 63100, Clermont-Ferrand
Centre Hospitalier Annecy Genevois
Unité de soin intensif, 1 Avenue De L Hopital, Bp 90074 Epagny Metz Tessy, Pringy Cedex
Centre Hospitalier De Cholet
Intensive Care Unit, 1 Rue De Marengo, 49300, Cholet
Centre Hospitalier Sud Francilien
Réanimation polyvalente, 40 Avenue Serge Dassault, 91100, Corbeil Essonnes
Assistance Publique Hopitaux De Paris
Réanimation médicale, 43 Boulevard De L Hopital, 75013, Paris
Assistance Publique Hopitaux De Paris
Réanimation Médicale, 20 Rue Leblanc, 75908, Paris Cedex 15
Centre Hospitalier Universitaire De Nantes
Anesthesie et soin intensif, Boulevard Du Professeur Jacques Monod, 44800, Saint Herblain
Groupe Hospitalier Du Sud Ile De France
Médecine Intensive et Réanimation, 270 Avenue Marc Jacquet, 77000, Melun
Assistance Publique Hopitaux De Paris
R3S- Médecine Intensive - réanimation, 43 Boulevard De L Hopital, 75013, Paris
Centre Hospitalier Universitaire De Saint Etienne
Intensive Care unit, Avenue Albert Raimond, 42270, Saint-Priest-En-Jarez
Hopital NOVO
Réanimation, 6 Avenue De L Ile De France, 95300, Pontoise
Departmental Hospital Vendee
Intensive Care unit, Boulevard Stephane Moreau, 85925, La Roche Sur Yon Cedex 9
Les Hopitaux Universitaires De Strasbourg
médecine intensive réanimation, 1 Place De L Hopital, Cs 80426, Strasbourg Cedex
Centre Hospitalier Universitaire De Dijon
medecine intensive réanimation, 14 Rue Paul Gaffarel, 21000, Dijon
Centre Hospitalier Universitaire De Bordeaux
Médecine intensive et réanimation, Place Amelie Raba Leon, 33000, Bordeaux
Centre Hospitalier Regional Universitaire De Tours
Médecine Intensive et Réanimation, 2 Boulevard Tonnelle, 37044, Tours Cedex 9
Centre Hospitalier Regional D'Angers
Médecine intensive Reanmination et Médecine hyperbare, 4 Rue Larrey, 49100, Angers
Centre Hospitalier Intercommunal De Poissy Saint Germain
medecine intensive réanimation, Residence Les Maisonnees, 10 Rue Du Champ Gaillard, Poissy
Centre Jean Perrin
Réanimation/USC, 58 Rue Montalembert, 63000, Clermont-Ferrand
Groupe Hospitalier Nord Essonne
réanimation polyvalente, ZAC De Corbeville, 1 Parvis De L Hopital, Orsay
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 |
|---|---|---|---|---|---|
| France | 2023-12-20 | 2023-12-20 | 2025-06-18 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 26 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | Pregnancy-form_2023-505108-52-00_COTRIVAP | 1 |
| Protocol (for publication) | Protocol_2023-505108-52-00_COTRIVAP_public | 3.0 |
| Protocol (for publication) | SAE-form_2023-505108-52-00_COTRIVAP | 1 |
| Recruitment arrangements (for publication) | 2023-505108-52-00_Recruitment-arrangements-COTRIVAP | 2 |
| Subject information and informed consent form (for publication) | 2023-505108-52-00_nifc1-patient_COTRIVAP | 2.0 |
| Subject information and informed consent form (for publication) | ni5-utilisation-donnees_2023-505108-52-00 | 1 |
| Subject information and informed consent form (for publication) | nifc2-proche_2023-505108-52-00 | 2.0 |
| Subject information and informed consent form (for publication) | nifc3-patient-poursuite_2023-505108-52-00 | 2.0 |
| Subject information and informed consent form (for publication) | nifc4-proche-poursuite_2023-505108-52-00 | 2.0 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC AZACTAM | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC AMOXICILLINE | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC AMOXICILLINE ACIDE CLAVULANIQUE | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC CEFEPIME | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC Cefotaxime | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC CEFTRIAXONE | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC CIPROFLOXACINE | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC COTRIMOXAZOLE | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC ERTAPENEM | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC IMIPENEM CILASTATINE | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC LEVOFLOXACINE | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC MEROPENEM | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC OFLOXACINE | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC PIPERACILLINE | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC PIPERACILLINE TAZOBACTAM | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC TEMOCILLINE | 1 |
| Synopsis of the protocol (for publication) | Protocol_synopsis_FR_2023-505108-52-00_COTRIVAP | 3.0 |
Application history
6 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-05-05 | France | Acceptable 2023-07-20
|
2023-07-20 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2023-08-18 | France | 2023-10-02 | |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2023-11-09 | France | Acceptable | 2023-12-11 |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2024-01-31 | France | 2024-03-18 | |
| 5 | SUBSTANTIAL MODIFICATION | SM-4 | 2024-06-21 | France | Acceptable 2024-08-23
|
2024-08-23 |
| 6 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-02-03 | France | Acceptable with conditions 2025-04-23
|
2025-04-23 |