Trial for the Treatment of Extensively Drug-Resistant Gram-negative Bacilli

Description

Approximately 444 subjects who are greater than or equal to 18 to 95 years of age, are non-pregnant, and are in the inpatient setting of one of the six study sites will be evaluated to treatment efficacy. Analysis will include subjects with bloodstream infection (BSI) or pneumonia due to at least one of the following gram-negative bacilli organisms: Acinetobacter baumannii, Klebsiella spp, Escherichia coli, Enterbactor spp. and/or Pseudomonas aeruginosa that demonstrates in vitro non-susceptibility defined as extensively drug-resistant Gram-negative bacilli (XDR-GNB) which includes XDR-AB, XDR-PA and CRE. If a subject has both BSI and pneumonia at the time of study enrollment, they will be included as a subject with pneumonia.

Objectives:

Primary:

  • Determine whether the treatment regimen of Colistimethate sodium (colistin) combined with Imipenem-cilistatin (imipenem) is associated with a decreased risk for mortality compared to colistin alone for patients with bloodstream infection (BSI) and/or pneumonia due to XDR-GNB.

Secondary:

  • Determine what treatment regimen (colistin monotherapy or colistin combined with imipenem) is more likely to reduce the emergence of colistin resistance among XDR-GNB isolates during therapy.

Study Start Date

October 2012

Estimated Completion Date

September 2017

Interventions

  • Drug: colistin and placebo
  • Drug: colistin and imipenem
  • Drug: colistin and meropenem

Specialties

  • Internal Medicine: Clinical Pharmacology,Infectious Disease
  • Infectious Disease: Antimicrobials,Cardiovascular,Pulm/Thoracic Infections
  • Pulmonology: Clinical Pharmacology,Pulm/Thoracic Infections
  • Pharmacy: Antimicrobials,Drug Interactions,Drug Trials
  • Emergency Medicine: Clinical Pharmacology,Infectious Disease
  • Hospitalist:

MeSH Terms

  • Colistin
  • Imipenem
  • Pneumonia
  • Sepsis

Study ID

Kaye, Keith, M.D., M.P.H. -- NIH 10-0065

Status

Unknown

Trial ID

NCT01597973

Study Type

Interventional

Trial Phase

Phase 3

Enrollment Quota

444

Sponsor

Kaye, Keith, M.D., M.P.H.

Inclusion Criteria

  • Hospitalized Adults (> 18 years to 95 years of age), at one of the study sites.
  • Diagnosis of BSI and/or pneumonia (VAP) (refer to Section 5.2.3 for definitions), due to a preliminary result of gram-negative non-lactose fermenter that is oxidase negative
  • or a final results of XDR-A. baumannii carbapenem-resistant Enterobacteriaciae or XDR
  • P. aeruginosa (refer to List of Abbreviations and Definition Section for pathogen definitions) and/or patients with suspected BSI and/or VAP and who have had a prior history (within last 6 months) of XDR-GNB that was susceptible to colistin. . o If final results do not indicate that the pathogen is an XDR-GNB, and identifies alternative treatment options, the patient would be eligible for the study if the subject is allergic to all the alternative treatment options.
  • Patients with polymicrobial respiratory or blood infections, including XDR-GNB and one or more pathogens, will be included in the study, as long as the XDR-GNB is determined to be a true pathogen (AB, CRE or PA). Other pathogens will be treated with antimicrobial agents as determined by the treating physician.
  • If more than one XDR-GNB study pathogens is identified as a study pathogen causing BSI and/or pneumonia, then the first study pathogen recovered will be considered as the primary study pathogen. If more than one study pathogen is recovered from the same culture, then the infection will be categorized as being caused by multiple study pathogens.
  • Patients with a life expectancy of > 24 hours
  • Signed written informed consent and HIPAA Authorization form

Exclusion Criteria

  • Female patients who are pregnant
  • Female patients who are nursing
  • Patients who are prisoners
  • Patients who are less than 18 years of age or greater than or equal to 96 years of age
  • Patients with neutropenia (WBC < 500 cells/mm3)
  • Patients who received G-CSF within 48 hours prior to enrollment
  • The presence of any of the following known clinical syndromes involving XDR-GNB as a pathogen which necessitate durations of antimicrobial therapies greater than 14 days: endocarditis, osteomyelitis, prosthetic joint infections, meningitis and/or other central nervous system infections.
  • Patients with a history of seizure disorder and are receiving anti-convulsive therapy.
  • Patients receiving valproic acid (with or without a known seizure disorder).
  • Patients who received 48 hours or more of colistin treatment (intravenous or inhaled [VAP]) within 72 hours of enrollment.
  • Patients who have end-stage renal disease requiring hemodialysis, will be excluded from evaluation pertaining to nephrotoxicity in the per protocol population.
  • Patients with known drug allergy to either of the study drugs

Gender

Both

Ages

18 Years to 95 Years

Accepts Healthy Volunteers

No

Study Locations and Contact Information (13)

Study Location Distance Name Phone Email
Mount Sinai Hospital - New York, New York 46.8 miles None None None
Mount Sinai Hospital - New York, New York 46.8 miles None None None
New York PresbyterianWeill Cornell Medical Center - New York, New York 50.7 miles None None None
Wayne State University - Detroit, Michigan 512.3 miles None None None
Wayne State University - Detroit, Michigan 512.3 miles Jolene Daniel 313-966-0045 jdanie@med.wayne.edu
Henry Ford Health System - Detroit, Michigan 513.4 miles None None None
Henry Ford Health System - Detroit, Michigan 513.4 miles None None None
Beaumont Health System - Royal Oak, Michigan 519.0 miles Matt Sims MD PhD 248-551-0027 matthew.sims@beaumont.edu
Beaumont Health System - Royal Oak, Michigan 519.0 miles None None None
The Ohio State University Wexner Medical Center - Columbus, Ohio 520.3 miles None None None
The Ohio State University Wexner Medical Center - Columbus, Ohio 520.3 miles None None None
Jackson Memorial HospitalJackson Health System - Miami, Florida 1,141.0 miles None None None
Jackson Memorial HospitalJackson Health System - Miami, Florida 1,141.0 miles Daniel Kett MD 305-585-6820 dkett@med.miami.edu

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