- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05696093
Efficacy of Cotrimoxazole as a De-escalation Treatment of Ventilator-Associated Pneumonia in Intensive Care Unit (COTRIVAP)
March 28, 2024 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
Recruiting
Conditions
Intervention / Treatment
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
Interventional
Enrollment (Estimated)
628
Phase
- 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
- Name: Damien Roux, MD-PhD
- Phone Number: 01.47.60.63.29
- Email: damien.roux@aphp.fr
Study Contact Backup
- Name: Aline DECHANET
- Phone Number: 01.40.25.78.30
- Email: aline.dechanet@aphp.fr
Study Locations
-
-
-
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:
- Stéphane GAUDRY
- Phone Number: 01 48 95 55 55
- Email: stephane.gaudry@aphp.fr
-
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:
- Saad NSEIR
- Phone Number: 03 20 44 40 84
- Email: saad.nseir@chru-lille.fr
-
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:
- Karim LAKHAL
- Phone Number: 02 53 48 27 85
- Email: karim.lakhal@chu-nantes.fr
-
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:
- Charles Edouard LUYT
- Phone Number: 01 42 16 38 24
- Email: charles-edouard.luyt@aphp.fr
-
Principal Investigator:
- Charles Edouard LUYT
-
Paris, France, 75015
- Recruiting
- Réanimation Médicale - Hôpital Européen Georges Pompidou
-
Contact:
- Jean-Luc DIEHL
- Phone Number: 01 56 09 32 01
- Email: jean-luc.diehl@aphp.fr
-
Principal Investigator:
- Jean-Luc DIEHL
-
Poissy, France, 78003
- Not yet recruiting
- Centre Hospitalier Intercommunal Saint-Germain-en-Laye
-
Contact:
- Jan HAYON
- Email: jhayon@chi-poissy-st-germain.fr
-
Principal Investigator:
- Jan HAYON
-
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:
- Mohamed FEJJAL
- Phone Number: 01 64 60 47 42
- Email: mfejjal@ch-provins.fr
-
Principal Investigator:
- Mohamed FEJJAL
-
Saint-Denis, France, 93200
- Not yet recruiting
- Médecin Intensive Réanimation - Hôpital Delafontaine
-
Contact:
- Daniel DA SILVA
- Phone Number: 01 42 35 61 40
- Email: daniel.silva@ch-stdenis.fr
-
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:
- Noémie ZUCMAN
- Email: nzucman@ch-annecygenevois.fr
-
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
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
- 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)
- 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 |
Intervention / Treatment |
---|---|
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.
|
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.
|
Use of standard antibiotic therapy for enterobacterial VAP
|
What is the study measuring?
Primary Outcome Measures
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
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.
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)
October 19, 2023
Primary Completion (Estimated)
October 31, 2026
Study Completion (Estimated)
December 31, 2026
Study Registration Dates
First Submitted
November 21, 2022
First Submitted That Met QC Criteria
January 23, 2023
First Posted (Actual)
January 25, 2023
Study Record Updates
Last Update Posted (Actual)
March 29, 2024
Last Update Submitted That Met QC Criteria
March 28, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Lung Diseases
- Disease Attributes
- Cross Infection
- Iatrogenic Disease
- Healthcare-Associated Pneumonia
- Pneumonia
- Pneumonia, Ventilator-Associated
- Anti-Infective Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Anti-Infective Agents, Urinary
- Anti-Bacterial Agents
- Trimethoprim, Sulfamethoxazole Drug Combination
Other Study ID 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
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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