Affordable Access

Access to the full text

A multicenter randomized placebo controlled trial of rifampin to reduce pedal amputations for osteomyelitis in veterans with diabetes (VA INTREPID)

Authors
  • Bessesen, Mary T.1, 2
  • Doros, Gheorghe3, 4
  • Henrie, Adam M.5
  • Harrington, Kelly M.3, 6
  • Hermos, John A.3, 6
  • Bonomo, Robert A.7, 8
  • Ferguson, Ryan E.3, 9
  • Huang, Grant D.10
  • Brown, Sheldon T.11, 12
  • 1 Department of Veterans Affairs Eastern Colorado Healthcare System, Denver, CO, USA , Denver (United States)
  • 2 University of Colorado – Denver, Aurora, CO, USA , Aurora (United States)
  • 3 Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, MA, USA , Boston (United States)
  • 4 Boston University, Boston, MA, USA , Boston (United States)
  • 5 Department of Veterans Affairs, Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Office of Research and Development, Albuquerque, NM, USA , Albuquerque (United States)
  • 6 Boston University School of Medicine, Boston, MA, USA , Boston (United States)
  • 7 Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, USA , Cleveland (United States)
  • 8 Case Western Reserve University, Cleveland, OH, USA , Cleveland (United States)
  • 9 Boston University School of Public Health, Boston, MA, USA , Boston (United States)
  • 10 Department of Veterans Affairs, Cooperative Studies Program Central Office, Washington, DC, USA , Washington (United States)
  • 11 James J. Peters VA Medical Center, New York, NY, USA , New York (United States)
  • 12 Icahn School of Medicine at Mt. Sinai, New York, NY, USA , New York (United States)
Type
Published Article
Journal
BMC Infectious Diseases
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Jan 08, 2020
Volume
20
Issue
1
Identifiers
DOI: 10.1186/s12879-019-4751-3
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundThe prevalence of diabetes mellitus continues to inexorably rise in the United States and throughout the world. Lower limb amputations are a devastating comorbid complication of diabetes mellitus. Osteomyelitis increases the risk of amputation fourfold and commonly presages death.Antimicrobial therapy for diabetic foot osteomyelitis (DFO) varies greatly, indicating that high quality data are needed to inform clinical decision making. Several small trials have indicated that the addition of rifampin to backbone antimicrobial regimens for osteomyelitis outside the setting of the diabetic foot results in 28 to 42% higher cure rates.Methods/designThis is a prospective, randomized, double-blind investigation of the addition of 6 weeks of rifampin, 600 mg daily, vs. matched placebo (riboflavin) to standard-of-care, backbone antimicrobial therapy for DFO. The study population are patients enrolled in Veteran Health Administration (VHA), ages ≥18 and ≤ 89 years with diabetes mellitus and definite or probable osteomyelitis of the foot for whom an extended course of oral or intravenous antibiotics is planned. The primary endpoint is amputation-free survival. The primary hypothesis is that using rifampin as adjunctive therapy will lower the hazard rate compared with the group that does not use rifampin as adjunctive therapy. The primary hypothesis will be tested by means of a two-sided log-rank test with a 5% significance level. The test has 90% power to detect a hazard ratio of 0.67 or lower with a total of 880 study participants followed on average for 1.8 years.DiscussionVA INTREPID will test if a rifampin-adjunctive antibiotic regimen increases amputation-free survival in patients seeking care in the VHA with DFO. A positive finding and its adoption by clinicians would reduce lower extremity amputations and their associated physical and emotional impact and reduce mortality for Veterans and for the general population with diabetic foot osteomyelitis. Given that rifampin-adjunctive regimens are currently employed for therapy for the majority of DFO cases in Europe, and only in a small minority of cases in the United States, the trial results will impact therapeutic decisions, even if the null hypothesis is not rejected.Trial registrationRegistered January 6, 2017 at ClinicalTrials.gov, NCT03012529.

Report this publication

Statistics

Seen <100 times