Trial of Colistin Versus Meropenem in Ventilator-associated Pneumonia (VAP) (CR-GNB)

Study Overview
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Brief Summary
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To demonstrate that colistin iv. is not inferior to meropenem in empiric treatment of VAP regarding the final point of primary efficacy: mortality in the 28 subsequent days and clinical healing in patients clinically evaluated. To compare the safety of treatment with colistin vs meropenem in VAP. To compare microbiological efficacy of treatment with colistin vs meropenem in VAP

Detailed Description
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Study drugs: Patients will be randomized a 1:1 rate and open label fashion to two interventions: group 1: colistin loading dose followed by colistin infusion iv/8h or group 2: meropenem 2 g/iv/ 8 h. The overall treatment time will be a minimum of 8 days. Follow-up visits will be performed at baseline, 72 h, 8 days, the end of treatment, and 28 days from recruitment ICU discharge, hospital discharge or death.

Official Title
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Randomized, Open Label, Multicenter, Non-inferiority Trial to Compare Safety and Efficacy of Colistin vs. Meropenem in VAP Caused by CR-GNB

Conditions
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Ventilator-associated Bacterial Pneumonia

Intervention / Treatment
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* Drug: Colistin
* Drug: Meropenem


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years with clinical and radiological criteria of VAP. The women of childbearing age (not surgically sterilized and in the period between menarche and 1 year after the menopause) must have a negative test of pregnancy in urine at the time of recruitment. The patient or his/her legal representative must sign a document of informed consent approved by the Ethics Review Committee. Exclusion Criteria: Hypersensitivity to the two antimicrobials of the study (colistin/meropenem). Renal insufficiency in substitute treatment. Corporal weight <40 kg or >150 kg. Patients previously included in another clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Colistin<br>Colistin 4.5 MU/iv.plus Colistin 3 MU/iv./8 h. 30 minutes infusion | Drug: Colistin<br>* Colistin 4.5 MU/iv plus Colistin 3 MU/iv./8 h. 30 minutes infusion<br>|
| Active Comparator: Meropenem<br>Meropenem 2 g/iv/ 8 h. 30 minutes infusion | Drug: Meropenem<br>* Meropenem 2 g/iv/ 8 h. 30 minutes infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients who die as a measure of efficacy | Demostrate that colistin iv. is not inferior to meropenen in empiric treatment of VAP regarding the final point of primary efficacy: mortality in the 28 subsequent days | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with clinical healing as a measure of efficacy | Demostrate that colistin is not inferior to meropenem in empiric treatment of VAP regarding efficacy: clinical healing in patients clinically evaluated | 28 days | 
| Microbiological resolution as a measure of microbiological efficacy | Compare microbiological efficacy of treatment with colistin vs meropenen in VAP. The putative pathogen is eliminated from repeated culture of lower respiratory tract. | 28 days | 
| Number of participants with adverse events as a measure of safety and tolerability | The evaluation of security will be carried out through collection of adverse events that occur during the trial | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VAP, MDR-GNB, colistin, meropenem