COTRIVAP - Efficacy of cotrimoxazole as a de-escalation treatment of Ventilator-Associated Pneumonia in intensive care unit

Phase 1

Recruiting

• Conditions: Intensive Care, Ventilator-associated Pneumonia; MedDRA version: 20.1Level: LLTClassification code: 10065153Term: Ventilator associated pneumonia Class: 10021881; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: CTIS2023-505108-52-00
• Lead Sponsor: Assistance Publique Hopitaux De Paris

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-05-05
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 628

Inclusion Criteria

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), Stability of haemodynamic (stability or decrease in catecholamine dose) and respiratory (stability or improvement of FIO2) parameters

Exclusion Criteria

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), 7)Limitation of life support (comfort care applied only) at the time of screening, 8)Enrolment to another interventional study on VAP care/management, 9)Pregnancy or breastfeeding

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: 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;Primary end point(s): vital status at day 28;Main Objective: To demonstrate that cotrimoxazole is non-inferior to best standard of care for the treatment of VAP in ICU.