Colistin and Rifampicin for MDR-Acinetobacter

NCT01577862 | Completed Phase 3 DMC

• 1 other identifier: FARM7X9F8K
• Study Type: interventional
• Target: 210
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Infection Due to Resistant Bacteria; Pneumonia, Ventilator-Associated; Hospital Acquired Pneumonia; Infection of Bloodstream; Infectious Disease of Abdomen

Keywords

ACINETOBACTER BAUMANNII; COLISTIN; RIFAMPICIN; THERAPY; RESISTANCE

Outcome Measures

Primary Outcomes (1)

• All cause mortality

  The study primary outcome is patient overall mortality, defined as death occurring during hospitalisation or within 30 days from randomization.

  30 day

Secondary Outcomes (5)

• Disease-specific death

  30 days after randomization

• Microbiological eradication

  30 day

• Hospitalization length

  From admission to hospital discharge, an average of 30 days

• Emergence of resistance to colistin

  From day 1 to the end of study evaluation, 30 days after randomization

• Toxicity

  From day 1 to the end of treatment evaluation, performed between day 10 and day 21

Study Arms (2)

Colistin

ACTIVE COMPARATOR

Colistin alone, 2 million units every 8 hours intravenously or according to renal function

Drug: Colistin

Colistin plus Rifampicin

EXPERIMENTAL

Colistin, 2 million units every 8 hours intravenously or according to renal function, plus Rifampicin, 600 mg every 12 hours intravenously

Drug: Colistin; Drug: Rifampicin

Interventions

Colistin DRUG

2 million units every 8 hours intravenously for at least 10 and up to a maximum of 21 days

Also known as: Sodium colistimethate

Colistin; Colistin plus Rifampicin

Rifampicin DRUG

600 mg every 12 hours intravenously

Also known as: Rifampin

Colistin plus Rifampicin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Campania Luigi Vanvitelli: lead
• Federico II University: collaborator

Related Publications (1)

• Durante-Mangoni E, Signoriello G, Andini R, Mattei A, De Cristoforo M, Murino P, Bassetti M, Malacarne P, Petrosillo N, Galdieri N, Mocavero P, Corcione A, Viscoli C, Zarrilli R, Gallo C, Utili R. Colistin and rifampicin compared with colistin alone for the treatment of serious infections due to extensively drug-resistant Acinetobacter baumannii: a multicenter, randomized clinical trial. Clin Infect Dis. 2013 Aug;57(3):349-58. doi: 10.1093/cid/cit253. Epub 2013 Apr 24.

  PMID: 23616495 DERIVED

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated; Healthcare-Associated Pneumonia; Sepsis; Intraabdominal Infections

Interventions

Colistin; colistinmethanesulfonic acid; Rifampin

Condition Hierarchy (Ancestors)

Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Systemic Inflammatory Response Syndrome; Inflammation

Intervention Hierarchy (Ancestors)

Polymyxins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Antimicrobial Cationic Peptides; Peptides; Amino Acids, Peptides, and Proteins; Antimicrobial Peptides; Pore Forming Cytotoxic Proteins; Membrane Proteins; Proteins; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic

Study Officials

• Riccardo Utili, MD

  University of Campania Luigi Vanvitelli

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 10, 2012
• First Posted: April 16, 2012
• Study Start: November 1, 2008
• Primary Completion: August 1, 2011
• Study Completion: October 1, 2011
• Last Updated: April 16, 2012

Record last verified: 2012-04