Colistin and Rifampicin for MDR-Acinetobacter (CoRAb)
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Purpose
Acinetobacter baumannii causes severe infections (pneumonia, bacteremia, organ space) with high lethality in hospitalised critically ill patients. It can acquire resistance to all classes of antibiotics (multidrug resistance, MDR) except an 'old' drug, colistin, which may be the only therapeutic option. However, colistin is not registered for this indication. The addition of rifampicin to colistin has been shown to be synergistic in vitro, and may be promising in vivo, but this combination has not been studied in comparison with colistin alone.
The purpose of this randomised, open-label, multicentre clinical trial is to assess whether the association of colistin and rifampicin reduces significantly the mortality of patients with severe MDR A. baumannii infections compared with colistin alone.
The trial will enroll 210 patients from intensive care units (ICU) of five tertiary care hospitals where MDR A. baumannii infection is endemic with epidemic phases. Patients will be randomly allocated to either colistin alone (control arm) or colistin plus rifampicin (experimental arm).
Primary end point is overall mortality, defined as death occurring within 30 days from randomisation.
Secondary end points will be disease-specific death, microbiological eradication, hospitalization length, emergence of resistance to colistin during treatment.
| Condition | Intervention | Phase |
|---|---|---|
|
Infection Due to Resistant Bacteria Pneumonia, Ventilator-Associated Hospital Acquired Pneumonia Infection of Bloodstream Infectious Disease of Abdomen |
Drug: Colistin Drug: Rifampicin |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Randomised, Open-Label Clinical Trial on The Efficacy of Colistin Plus Rifampicin Treatment Versus Colistin Alone for Severe Infections Due to Multidrug-Resistant Acinetobacter Baumannii |
- All cause mortality [ Time Frame: 30 day ] [ Designated as safety issue: No ]The study primary outcome is patient overall mortality, defined as death occurring during hospitalisation or within 30 days from randomization.
- Disease-specific death [ Time Frame: 30 days after randomization ] [ Designated as safety issue: No ]Disease-specific death or A. baumannii infection-related death is defined as death occurring in the presence of persistent signs and symptoms of A. baumannii infection (persistent pneumonia, septic shock) and/or when it occurs within the first week of antibiotic treatment without any other clear explanation.
- Microbiological eradication [ Time Frame: 30 day ] [ Designated as safety issue: No ]Microbiological eradication is defined as the disappearance of A. baumannii in cultures from blood, bronchial aspirate, urines and drainage fluids.
- Hospitalization length [ Time Frame: From admission to hospital discharge, an average of 30 days ] [ Designated as safety issue: No ]Hospitalization length is calculated as days in the hospital as well as days in the intensive care unit since diagnosis of A. baumannii infection.
- Emergence of resistance to colistin [ Time Frame: From day 1 to the end of study evaluation, 30 days after randomization ] [ Designated as safety issue: No ]Emergence of resistance is defined as the detection during treatment of an A. baumannii isolate showing resistance to colistin (MIC >2 mg/l).
- Toxicity [ Time Frame: From day 1 to the end of treatment evaluation, performed between day 10 and day 21 ] [ Designated as safety issue: Yes ]Renal toxicity is defined as decrease of creatinine clearance below 50 ml/min or >50% reduction in the creatinine clearance relative to the baseline. Hepatic toxicity is defined as increase of direct bilirubin above 3 mg/dl.
| Enrollment: | 210 |
| Study Start Date: | November 2008 |
| Study Completion Date: | October 2011 |
| Primary Completion Date: | August 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Colistin
Colistin alone, 2 million units every 8 hours intravenously or according to renal function
|
Drug: Colistin
2 million units every 8 hours intravenously for at least 10 and up to a maximum of 21 days
Other Name: Sodium colistimethate
|
|
Experimental: Colistin plus Rifampicin
Colistin, 2 million units every 8 hours intravenously or according to renal function, plus Rifampicin, 600 mg every 12 hours intravenously
|
Drug: Colistin
2 million units every 8 hours intravenously for at least 10 and up to a maximum of 21 days
Other Name: Sodium colistimethate
Drug: Rifampicin
600 mg every 12 hours intravenously
Other Name: Rifampin
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- clinical and microbiological evidence of a severe infection due to multi-drug resistant A. baumannii during hospitalization
- susceptibility of the A. baumannii isolate to colistin (MIC < or =2 mg/l).
Exclusion Criteria:
- age below 18 years
- treatment with one of the study drugs prior to the diagnosis of A. baumannii infection
- severe liver dysfunction
- history of prior hypersensitivity to the study drugs
Contacts and Locations More Information
No publications provided
| Responsible Party: | Riccardo Utili, Professor, Second University of Naples |
| ClinicalTrials.gov Identifier: | NCT01577862 History of Changes |
| Other Study ID Numbers: | FARM7X9F8K |
| Study First Received: | April 10, 2012 |
| Last Updated: | April 12, 2012 |
| Health Authority: | Italy: The Italian Medicines Agency |
Keywords provided by Second University of Naples:
|
ACINETOBACTER BAUMANNII COLISTIN RIFAMPICIN THERAPY RESISTANCE |
Additional relevant MeSH terms:
|
Communicable Diseases Infection Pneumonia Pneumonia, Ventilator-Associated Lung Diseases Respiratory Tract Diseases Respiratory Tract Infections Cross Infection Ventilator-Induced Lung Injury Lung Injury Colistin |
Rifampin Anti-Bacterial Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Antibiotics, Antitubercular Antitubercular Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Leprostatic Agents Nucleic Acid Synthesis Inhibitors |
ClinicalTrials.gov processed this record on May 23, 2013