Efficacy of Cotrimoxazole as a De-escalation Treatment of Ventilator-Associated Pneumonia in Intensive Care Unit (COTRIVAP)

May 15, 2025 updated by: Assistance Publique - Hôpitaux de Paris

Efficacy of Cotrimoxazole as a De-escalation Treatment of Ventilator-Associated Pneumonia in Intensive Care Unit. Multicentric Non-inferiority Randomised Controlled Trial

Efficacy of cotrimoxazole as a de-escalation treatment for adult patients Ventilator-Associated Pneumonia in intensive care unit Multicentre randomized non-inferiority trial comparing cotrimoxazole to standard antibiotic therapy for enterobacterial VAP

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Multicentre randomized non-inferiority trial comparing cotrimoxazole to standard antibiotic therapy for enterobacterial VAP. Selection of patients will be done by physicians in ICU. All clinically suspected VAP will be confirmed with a lung sample (preferably bronchoalveolar lavage or protected distal specimen, otherwise endotracheal aspiration). Patients with a microbiologically confirmed VAP due to an Enterobacteriaceae susceptible to cotrimoxazole and at least one antibiotic of the empiric antibiotic therapy (based on international recommendations) will be included. After written informed consent, they will be randomized (1:1), using a computer-generated randomization scheme of various-sized blocks, stratified by presence of septic shock at VAP diagnosis and by presence of COVID-19 pneumonia on ICU admission, through a centralized 24 hours internet service (CleanWEB™) to cotrimoxazole, or best standard of care (either a beta-lactam or a fluoroquinolone), after randomization for a total duration of 7 days (including empiric initial appropriate treatment). Posology and modalities of antibiotic administration will be optimized based on most recent recommendations for ICU patients. Because antibiotic therapy will be variable in the control group, single or double blind is not appropriate. Daily follow-up until death or ICU discharge or day 28 will be performed (vital status, antibiotic therapy, new infection, Clostridium-difficile infection). Clinical (arterial blood gas, temperature, haematology, tracheal secretions) and radiological cure (chest X-ray) will be assessed at Day 7. Systematic MDR bacteria screening will be performed weekly and at ICU discharge. Vital status will be assessed at day 90. Alive patients leaving ICU before 90 days will be contacted by phone (if discharge at home) or by interview at hospital (if transferred in a different ward). Assessment of the clinical and radiological cure by an independent committee (1 specialist in infectious disease and 1 intensivist), blinded of the randomization arm (PROBE methodology).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
628

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • France
      • Amiens, France, 80054
        • Active, not recruiting
        • Médecine Intensive Réanimation - Centre Hospitalier Universitaire Amiens-Picardie
      • Angers, France, 49100
        • Active, not recruiting
        • Médecine Intensive Réanimation - Centre Hospitalier Universitaire Angers
      • Bobigny, France, 93000
        • Not yet recruiting
        • Réanimation Médico-chirurgicale - Hôpital Avicenne
        • Contact:
        • Principal Investigator:
          • Stéphane GAUDRY
      • Bordeaux, France, 33000
        • Active, not recruiting
        • Médecine Intensive Réanimation - CHU Bordeaux - Hôpital Pellegrin
      • Boulogne-Billancourt, France, 92100
        • Active, not recruiting
        • Réanimation Médico-chirurgicale - Hôpital Ambroise-Paré
      • Béthune, France, 62660
        • Active, not recruiting
        • Médecine Intensive Réanimation - Centre Hospitalier Béthune - Beuvry
      • Cholet, France, 49300
        • Active, not recruiting
        • Réanimation polyvalente et Unité de surveillance continue - Centre Hospitalier de Cholet
      • Clermont-Ferrand, France, 63003
        • Active, not recruiting
        • Réanimation Médicale - Centre Jean Perrin - Site Gabriel Montpied
      • Colombes, France, 92700
        • Active, not recruiting
        • Médecine Intensive Réanimation - Hôpital Louis Mourier
      • Corbeil-Essonnes, France, 91100
        • Active, not recruiting
        • Réanimation polyvalente et surveillance continus - Centre Hospitalier Sud Francilien
      • Dijon, France, 21079
        • Active, not recruiting
        • Médecine Intensive Réanimation - Hôpital François Mitterrand
      • La Roche-sur-Yon, France, 85000
        • Active, not recruiting
        • Médecine Intensive Réanimation - Centre Hospitalier Départemental Vendée
      • La Tronche, France, 38700
        • Active, not recruiting
        • Médecine Intensive Réanimation - Hôpital Michallon
      • Lille, France, 59037
        • Not yet recruiting
        • Réanimation Médicale - Hôpital Robert Salengro
        • Principal Investigator:
          • Saad NSEIR
        • Contact:
      • Longjumeau, France, 91160
        • Active, not recruiting
        • Réanimation médicale - Centre Hospitalier de Longjumeau
      • Melun, France, 77000
        • Active, not recruiting
        • Réanimation et Surveillance continue - Centre Hospitalier de Melun
      • Nancy, France, 54000
        • Active, not recruiting
        • Médecine Intensive Réanimation - CHRU de Nancy - Hôpitaux de Brabois
      • Nantes, France, 44093
        • Not yet recruiting
        • Réanimation Médicale et Maladies Infectieuses - Hôpital Laennec
        • Contact:
        • Principal Investigator:
          • Karim Lakhal
      • Paris, France, 75013
        • Active, not recruiting
        • Médecine Intensive et Réanimation - Hôpital de la Pitié Salpêtrière
      • Paris, France, 75013
        • Recruiting
        • Réanimation Médicale - Hôpital de la Pitié Salpêtrière
        • Contact:
        • Principal Investigator:
          • Charles Edouard LUYT
      • Paris, France, 75015
        • Recruiting
        • Réanimation Médicale - Hôpital Européen Georges Pompidou
        • Contact:
        • Principal Investigator:
          • Jean-Luc DIEHL
      • Poissy, France, 78003
        • Active, not recruiting
        • Centre Hospitalier Intercommunal Saint-Germain-en-Laye
      • Pontoise, France, 93500
        • Active, not recruiting
        • Médecine Intensive Réanimation - Hôpital René Dubos
      • Provins, France, 77160
        • Not yet recruiting
        • Médecine Intensive Réanimation - Centre Hospitalier Léon Binet
        • Contact:
        • Principal Investigator:
          • Mohamed FEJJAL
      • Saint-Denis, France, 93200
        • Not yet recruiting
        • Médecin Intensive Réanimation - Hôpital Delafontaine
        • Contact:
        • Principal Investigator:
          • Daniel da Silva
      • Saint-Priest-en-Jarez, France, 42270
        • Active, not recruiting
        • Réanimation Polyvalente - Centre Hospitalier Universitaire Nord Saint-Etienne
      • Strasbourg, France, 67091
        • Active, not recruiting
        • Médecine Intensive Réanimation - Nouvel Hôpital Civil
      • Toulon, France, 83056
        • Active, not recruiting
        • Réanimation Polyvalente - Hôpital Sainte Musse
      • Tours, France, 37000
        • Active, not recruiting
        • Médecine Intensive Réanimation - Hôpital Bretonneau
      • Épagny, France, 74370
        • Not yet recruiting
        • Réanimation Polyvalente - Centre Hospitalier Annecy Genevois
        • Contact:
        • Principal Investigator:
          • Noémie ZUCMAN

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adult patients hospitalized in an ICU
  • Under mechanical ventilation for at least five days
  • Microbiologically confirmed VAP preferably on a distal lung sample (bronchoalveolar lavage or protected distal specimen) otherwise endotracheal aspiration
  • Enterobacteriaceae susceptible to cotrimoxazole, and for polymicrobial VAP, all bacteria susceptible to cotrimoxazole
  • 5) Treated for at least 24 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:

  • Haemodynamic instability (increasing dose of a catecholamine in the last 24 hours)

  • Contra-indication to cotrimoxazole:

    • allergy,
    • advanced liver insufficiency,
    • renal dysfunction with clearance <15 mL/min/1.73 m² without hemodialysis
    • G6PD deficiency
    • history of hypersensitivity to one of the components (in particular, hypersensitivity to sulphonamides
    • known macrocytic anemia defined by VGM >
    • treatment with methotrexate
  • Infection requiring prolonged antibiotic-therapy (pleural empyema, lung abscess, necrotizing pneumonia, etc…)
  • Cystic fibrosis
  • Immunosuppression (neutropenia, HIV with CD4 lymphocytes below 200/mm3, immunosuppressive therapy or corticosteroid therapy >0.5 mg/kg/j before ICU admission)
  • Cardiac arrest without awakening
  • Moribund state (patient likely to die within 24h)
  • Limitation of life support (comfort care applied only) at the time of screening
  • Enrolment to another interventional study on VAP care/management
  • Pregnancy or breastfeeding
  • Subject deprived of freedom, subject under a legal protective measure
  • No affiliation to any health insurance system
  • Refusal to participate to the study (patient or legal representative or family member or close relative if present)
  • Patients previously included in the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: cotrimoxazole
Use of cotrimoxazole for enterobacterial VAP. Posology and modalities of antibiotic administration will be optimized based on most recent recommendations for ICU patient. They will receive the treatment for 28 days or until death or until ICU discharge if its before 28days.
Drug: cotrimoxazole
Use of cotrimoxazole therapy for enterobacterial VAP
Active Comparator: standard antibiotic therapy
Use of standard antibiotic therapy enterobacterial VAP. Posology and modalities of antibiotic administration will be optimized based on most recent recommendations for ICU patient. They will receive the treatment for 28 days or until death or until ICU discharge if its before 28days.
Drug: standard antibiotic therapy
Use of standard antibiotic therapy for enterobacterial VAP

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
To demonstrate that cotrimoxazole is non-inferior to best standard of care for the treatment of VAP in ICU in term of survival at day 28
Time Frame: 28 days after inclusion
Vital status at day 28
28 days after inclusion

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
To demonstrate that cotrimoxazole is superior to best standard of care for the treatment of VAP in ICU in term of mortality at day 90
Time Frame: 90 days after inclusion
Vital status at day 90
90 days after inclusion
To demonstrate that cotrimoxazole is superior to best standard of care for the treatment of VAP in IC in terms of mechanical ventilation (MV)-free-days at day 28
Time Frame: 28 days after inclusion
number of MV-free-days through day 28
28 days after inclusion
To demonstrate that cotrimoxazole is superior to best standard of care for the treatment of VAP in ICU in terms of rate of cure between days 7 and 10
Time Frame: days 7 and 10 after inclusion
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)
days 7 and 10 after inclusion
To demonstrate that cotrimoxazole is superior to best standard of care for the treatment of VAP in ICU in terms of VAP recurrence
Time Frame: 28 days after inclusion
new episode of VAP with the same Enterobacteriaceae
28 days after inclusion
To demonstrate that cotrimoxazole is superior to best standard of care for the treatment of VAP in ICU in terms of ICU length of stay
Time Frame: 28 days after inclusion
ICU length of stay
28 days after inclusion
To demonstrate that cotrimoxazole is superior to best standard of care for the treatment of VAP in ICU in terms of hospital length of stay
Time Frame: 28 days after inclusion
hospital length of stay
28 days after inclusion
To assess the safety of cotrimoxazole compared to best standard of care at day 28 in terms of allergy to antibiotics
Time Frame: 28 days after inclusion
safety (rate of allergy due to antimicrobial drug)
28 days after inclusion
To demonstrate that cotrimoxazole is superior to best standard of care for the treatment of VAP in ICU in terms of mortality at day 28
Time Frame: 28 days after inclusion
Vital status at day 28
28 days after inclusion
To demonstrate that cotrimoxazole is superior to best standard of care for the treatment of VAP in ICU in terms of overall antibiotic consumption
Time Frame: day 28 after inclusion
antibiotic-free days at day 28
day 28 after inclusion
To assess the ecological impact of the treatment in terms of acquisition of MDR bacteria in ICU
Time Frame: 28 days after inclsuion
evolution of rate of MDR bacterial colonization on systematic screening at enrolment until ICU discharge
28 days after inclsuion
To assess the ecological impact of the treatment in terms of rate of Clostridioides difficile infection
Time Frame: 28 days after inclusion
diagnostic of Clostridioides difficile infection between inclusion and day 28
28 days after inclusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique - Hôpitaux de Paris

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 19, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 31, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 21, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 23, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 25, 2023

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 20, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 15, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • APHP220799

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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