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

Sponsor

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla (Other)

Overall Status

Completed

CT.gov ID

NCT01292031

Collaborator

European Commission (Other)

232

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Ventilator-associated Bacterial Pneumonia	Drug: Colistin Drug: Meropenem	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

232 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2012

Actual Primary Completion Date :

Dec 1, 2015

Actual Study Completion Date :

Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Colistin Colistin 4.5 MU/iv.plus Colistin 3 MU/iv./8 h. 30 minutes infusion	Drug: Colistin Colistin 4.5 MU/iv plus Colistin 3 MU/iv./8 h. 30 minutes infusion
Active Comparator: Meropenem Meropenem 2 g/iv/ 8 h. 30 minutes infusion	Drug: Meropenem Meropenem 2 g/iv/ 8 h. 30 minutes infusion

Arm

Intervention/Treatment

Experimental: Colistin

Colistin 4.5 MU/iv.plus Colistin 3 MU/iv./8 h. 30 minutes infusion

Drug: Colistin

Colistin 4.5 MU/iv plus Colistin 3 MU/iv./8 h. 30 minutes infusion

Active Comparator: Meropenem

Meropenem 2 g/iv/ 8 h. 30 minutes infusion

Drug: Meropenem

Meropenem 2 g/iv/ 8 h. 30 minutes infusion

Outcome Measures

Primary Outcome Measures

Number of patients who die as a measure of efficacy [28 days]
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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital of Alexandroupolis, Medical School University of Thrace	Alexandroupolis		Greece
2	Evagelismos Hospital, Medical School University of Athens	Athens		Greece
3	General Hospital of Larissa, Thessalia University	Athens		Greece
4	Sotiria Hospital, Medical School University of Athens	Athens		Greece
5	University Hospital Ag. Anargiri, Nurshing School University of Athens	Athens		Greece
6	University Hospital ATTIKON, Medical School University of Athens	Athens		Greece
7	University Hospital of Larissa, Medical School University of Athens	Athens		Greece
8	University Hospital of Heraklion, Medical School University of Crete	Crete		Greece
9	University Hospital of Ioannina, Medical School, University of Ipirus	Ioannina		Greece
10	Papanikolaou Hospital,	Thessaloniki		Greece
11	Azienda OspedalieraSant'Andrea	Roma	Rome	Italy
12	AO Ospedale Niguarda Ca Granda Milano	Milan		Italy
13	University of Napoli Federico II	Napoli		Italy
14	AOU Cisanello- Pisa	Pisa		Italy
15	Policlinico Universitario A. Gemelli	Roma		Italy
16	S.Giovanni Battista Molinette Hospital Turin	Turin		Italy
17	Complexo Hospitalario A Coruña	A Coruña		Spain	15006
18	Hospital General Universitario Santa Lucía	Cartagena		Spain
19	Hospital General de Ciudad Real	Ciudad Real		Spain
20	Hospital Puerta del Mar Universidad de Cádiz	Cádiz		Spain
21	University Hospital Reina Sofía	Córdoba		Spain	14004
22	University Hospital Juan Ramón Jiménez	Huelva		Spain	21005
23	Hospital de Jerez	Jerez de la Frontera		Spain
24	Hospital 12 de Octubre	Madrid		Spain
25	Hospital Clínico San Carlos	Madrid		Spain
26	Hospital Carlos Haya Universidad de Málaga	Málaga		Spain
27	Hospital Universitario Virgen de la Victoria	Málaga		Spain
28	Complexo Hospitalario de Orense	Orense		Spain
29	Hospital Marqués de Valdecillas	Santander		Spain
30	Hospital Virgen del Rocío Sevilla	Seville		Spain	41013
31	Hospital Mutua de Terrassa	Tarrasa		Spain	08221
32	La Fe Universidad de Valencia	Valencia		Spain	46009
33	Hospital Dr. Peset	Valencia		Spain	46017