Clinical trial NCT01292031: Trial of Colistin Versus Meropenem in Ventilator-associated Pneumonia (VAP) (CR-GNB)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ventilator-associated Bacterial Pneumonia
Keywords: VAP
MDR-GNB
colistin
meropenem
Lead sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor class: OTHER
Collaborators: name: European Commission
First posted: 2011-02-09
Enrollment: 232
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 1. 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.
2. To compare the safety of treatment with colistin vs meropenem in VAP.
3. To compare microbiological efficacy of treatment with colistin vs meropenem in VAP

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of patients who die as a measure of efficacy
timeFrame: 28 days
Secondary outcomes:
measure: Number of patients with clinical healing as a measure of efficacy
timeFrame: 28 days
measure: Microbiological resolution as a measure of microbiological efficacy
timeFrame: 28 days
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: 28 days
Other outcomes:
Locations:
city: Alexandroupolis
country: Greece
facility: University Hospital of Alexandroupolis, Medical School University of Thrace
city: Athens
country: Greece
facility: Evagelismos Hospital, Medical School University of Athens
city: Athens
country: Greece
facility: General Hospital of Larissa, Thessalia University
city: Athens
country: Greece
facility: Sotiria Hospital, Medical School University of Athens
city: Athens
country: Greece
facility: University Hospital Ag. Anargiri, Nurshing School University of Athens
city: Athens
country: Greece
facility: University Hospital ATTIKON, Medical School University of Athens
city: Athens
country: Greece
facility: University Hospital of Larissa, Medical School University of Athens
city: Crete
country: Greece
facility: University Hospital of Heraklion, Medical School University of Crete
city: Ioannina
country: Greece
facility: University Hospital of Ioannina, Medical School, University of Ipirus
city: Thessaloniki
country: Greece
facility: Papanikolaou Hospital,
city: Roma
country: Italy
facility: Azienda OspedalieraSant'Andrea
state: Rome
city: Milan
country: Italy
facility: AO Ospedale Niguarda Ca Granda Milano
city: Napoli
country: Italy
facility: University of Napoli Federico II
city: Pisa
country: Italy
facility: AOU Cisanello- Pisa
city: Roma
country: Italy
facility: Policlinico Universitario A. Gemelli
city: Turin
country: Italy
facility: S.Giovanni Battista Molinette Hospital Turin
city: A Coruña
country: Spain
facility: Complexo Hospitalario A Coruña
city: Cartagena
country: Spain
facility: Hospital General Universitario Santa Lucía
city: Ciudad Real
country: Spain
facility: Hospital General de Ciudad Real
city: Cádiz
country: Spain
facility: Hospital Puerta del Mar Universidad de Cádiz
city: Córdoba
country: Spain
facility: University Hospital Reina Sofía
city: Huelva
country: Spain
facility: University Hospital Juan Ramón Jiménez
city: Jerez de la Frontera
country: Spain
facility: Hospital de Jerez
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Málaga
country: Spain
facility: Hospital Carlos Haya Universidad de Málaga
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Orense
country: Spain
facility: Complexo Hospitalario de Orense
city: Santander
country: Spain
facility: Hospital Marqués de Valdecillas
city: Seville
country: Spain
facility: Hospital Virgen del Rocío Sevilla
city: Tarrasa
country: Spain
facility: Hospital Mutua de Terrassa
city: Valencia
country: Spain
facility: La Fe Universidad de Valencia
city: Valencia
country: Spain
facility: Hospital Dr. Peset
Study officials:
affiliation: Andaluz Health Service
name: José Miguel Cisneros-Herreros, PhD
role: STUDY_CHAIR
References:
citation: Cisneros JM, Rosso-Fernandez CM, Roca-Oporto C, De Pascale G, Jimenez-Jorge S, Fernandez-Hinojosa E, Matthaiou DK, Ramirez P, Diaz-Miguel RO, Estella A, Antonelli M, Dimopoulos G, Garnacho-Montero J; Magic Bullet Working Group WP1. Colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia (Magic Bullet study): an investigator-driven, open-label, randomized, noninferiority controlled trial. Crit Care. 2019 Nov 28;23(1):383. doi: 10.1186/s13054-019-2627-y.
citation: Rosso-Fernandez C, Garnacho-Montero J, Antonelli M, Dimopoulos G, Cisneros JM; MagicBullet study group. Safety and efficacy of colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia as part of a macro-project funded by the Seventh Framework Program of the European Commission studying off-patent antibiotics: study protocol for a randomized controlled trial. Trials. 2015 Mar 20;16:102. doi: 10.1186/s13063-015-0614-4.