Colistin and Rifampicin for MDR-Acinetobacter (CoRAb)

This study has been completed.
Sponsor:
Collaborator:
Federico II University
Information provided by (Responsible Party):
Riccardo Utili, Second University of Naples
ClinicalTrials.gov Identifier:
NCT01577862
First received: April 10, 2012
Last updated: April 12, 2012
Last verified: April 2012
  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

Resource links provided by NLM:


Further study details as provided by Second University of Naples:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01577862

Sponsors and Collaborators
Second University of Naples
Federico II University
Investigators
Principal Investigator: Riccardo Utili, MD Second University of Naples
  More Information

No publications provided by Second University of Naples

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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:
Infection
Communicable Diseases
Pneumonia
Pneumonia, Ventilator-Associated
Intraabdominal Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Cross Infection
Ventilator-Induced Lung Injury
Lung Injury
Rifampin
Colistin
Antibiotics, Antitubercular
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 30, 2014