Multicenter Open-label Randomized Controlled Trial (RCT) to Compare Colistin Alone Versus Colistin Plus Meropenem

Gram-Negative Bacterial Infections Clinical Trial

Official title:

Multicenter Open-label RCT to Compare Colistin Alone vs. Colistin Plus Meropenem

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01732250
• Other study ID #: 0276-12-RMC
• Status: Completed
• Phase: Phase 4
• First received: November 19, 2012
• Last updated: April 10, 2017
• Start date: March 2013
• Est. completion date: February 28, 2017

Study information

• Verified date: April 2017
• Source: Rabin Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether the addition of meropenem to colistin is better than colistin alone in the treatment of clinically significant infections caused by multi-drug resistant bacteria

Recruitment information / eligibility

• Status: Completed
• Enrollment: 406
• Est. completion date: February 28, 2017
• Est. primary completion date: January 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult inpatients

• Clinically significant, microbiological-documented infection caused by carbapenem-resistant and colistin-susceptible Gram-negative bacteria and identified according to CDC criteria- blood stream infections, hospital acquired pneumonia, ventilator associated pneumonia, and urinary tract infections

• Patient recruitment will occur only after microbiological documentation and susceptibility testing. Patients will be included within 96 hours of the time the index culture was taken (typically within 48 hours of isolate identification), regardless of the antibiotic treatment administered during this time period.

Exclusion Criteria:

• Previous inclusion in the trial. Patients will be included in the RCT only once for the first identified episode of infection

• Pregnant women

• Epilepsy or prior seizures

• Known allergy to colistin or a carbapenem

Related Conditions & MeSH terms

• Bacterial Infections
• Gram-Negative Bacterial Infections

Intervention

Drug:
• Colistin
IV Colistin with loading dose of 9 mil IU units, Maintenance dose 4.5 mil IU q12h, adjusted for renal function, for 10 days.
• Meropenem
IV meropenem, 2 gram q8h, adjusted for renal function, for up to 10 days.

Locations

Country	Name	City	State
Greece	Atikkon Hospital	Athens
Greece	Laikon Hosptial	Athens
Israel	Rambam Health Care Center	Haifa
Israel	Rabin Medical Center	Petach-Tikvah
Israel	Tel-Aviv Sourasky Medical Center	Tel-Aviv
Italy	Monaldi Hospital, University of Naples S.U.N.	Naples
Italy	Agostino Gemelli Hospital	Rome

Sponsors (2)

Lead Sponsor	Collaborator
Mical Paul	European Commission

Countries where clinical trial is conducted

Greece,  Israel,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical success	defined as a composite of all of the following, all measured at 14 days: Patient alive; Systolic blood pressure >90 mmHg without need for vasopressor support; Stable or improved SOFA score, define as: for baseline SOFA = 3: a decrease of at least 30%; for baseline SOFA <3: stable or decreased SOFA score; For patients with HAP/ VAP, PaO2/FiO2 ratio stable or improved; For patients with bacteremia, no growth of the initial isolate in blood cultures taken on day 14 if patient still febrile	14 days
Secondary	Secondary outcomes and adverse events	14 and 28-day all-cause mortality.; If patients are discharged or death occurs before end of follow-up (day 28), we will end data collection at that date. We will attempt to determine survival status at day 28 for all patients (central registry in Israel; re-admissions, rehabilitation centers, hospital transfers in Greece and Italy).	14 and 28 days
Secondary	Clinical success with modification	Clinical success, but with modification to the antibiotic treatment not permitted by protocol	14 days
Secondary	Time to defervescence	defined as time to reach a temperature of <38°C with no recurrence for 3 days	28 days
Secondary	Time to weaning	Time to weaning from mechanical ventilation in VAP for patients weaned alive	28 days
Secondary	Time to hospital discharge	Time to hospital discharge for patient discharged alive	28 days
Secondary	Microbiological failure	Microbiological failure, defined as isolation of the initial isolate (phenotypically identical) in a clinical sample (blood or other) 7 days or more after start of treatment or its identification in respiratory samples.; For all patients with VAP/ HAP sputum or tracheal aspirates will be obtained on day 7, regardless of clinical response; For all patients with UTI, a repeat urine culture will be obtained on day 7, regardless of clinical response; For patients with bacteremia, blood cultures will be repeated on day 7 and 14, only if the patient is febrile at that time	28 days
Secondary	Superinfections	Defined as a new clinically or microbiologically-documented infections by CDC criteria within 28 days	28 days
Secondary	New resistant infection	Colonization or infection by newly-acquired (other species than the initial infection) carbapenem-resistant or colistin-resistant Gram-negative bacteria. Colonization will be assessed by rectal surveillance	28 days
Secondary	CDAD	Clostridium-difficile-associated diarrhea, defined by diarrhea with a positive C. difficile toxin test	28 days