Investigation of Rifampin to Reduce Pedal Amputations for Osteomyelitis in Diabetics

NCT03012529 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: 2001
• Study Type: interventional
• Target: 843
• Locations: 1 country
• Sites: 30

Brief Summary

The purpose of this research study is to determine if rifampin, an antibiotic (a medicine that treats infections), is effective in treating osteomyelitis (infection of the bone) of the foot in diabetic patients. Despite use of powerful antibiotics prescribed over a long period of time, many diabetic patients remain at a high risk for needing an amputation of part of the foot or lower leg because the osteomyelitis is not cured. Some small research studies have shown that addition of rifampin to other antibiotics is effective in treating osteomyelitis in both diabetics and non-diabetics. However, because few diabetics with osteomyelitis have been studied, there is no definite proof that it is better than the usual treatments for diabetic patients. If this study finds that adding rifampin to the usual antibiotics prescribed for osteomyelitis reduces the risk for amputations, doctors will be able to more effectively treat many Veteran patients with this serious infection. Improving treatment outcomes is an important healthcare goal of the VA.

Conditions

Osteomyelitis; Diabetes; Amputation

Keywords

Rifampin; Double-blind; Clinical Trial; Veterans; Diabetes

Outcome Measures

Primary Outcomes (1)

• Amputation-Free Survival

  The primary endpoint is amputation-free survival, ending with amputation or death from any cause. Amputation is defined as surgical treatment of osteomyelitis by removal or debridement of necrotic/infected bone (all or part of a bone) from a lower extremity limb or digit on the ipsilateral side of the protocol-treated osteomyelitis. Debridement prior to randomization may include removal of bone. Because this debridement occurs early, prior to exposure to study drug or placebo, removal of bone at that time is not a study endpoint.

  Assessed 2 years post intervention

Secondary Outcomes (11)

• Time to Amputation

  Assessed 2 years post intervention

• New course of antibacterial therapy for ipsilateral foot infection

  Assessed 2 years post intervention

• Quality of Life - SF-36

  Assessed 12 months post intervention

• Ambulatory Status

  Assessed 12 months post intervention

• Incidence of Falls

  Assessed 12 months post intervention

Study Arms (2)

Active drug

ACTIVE COMPARATOR

Patients receive oral adjunctive rifampin therapy

Drug: Rifampin

Placebo

PLACEBO COMPARATOR

Patients receive oral riboflavin

Drug: Riboflavin Placebo

Interventions

Rifampin DRUG

Subjects who are randomly assigned to adjunctive rifampin will receive a 600 mg oral daily dose targeted for a six-week period. If a subject experiences gastrointestinal intolerance on once daily dosing, the study drug may be administered as rifampin 300 mg twice a day.

Active drug

Riboflavin Placebo DRUG

A placebo capsule will be administered daily to match frequency and duration of rifampin interventional drug. For the purpose of mimicking urine discoloration when taking rifampin, riboflavin will be added to the placebo to produce a urine discoloration effect.

Placebo

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 and 89 years
• Diagnosis of diabetes mellitus, either by: 1) use of oral hypoglycemic agents or insulin at the time of enrollment; 2) a hemoglobin A1c (HgA1c) level within the past 90 days \> 6.5; or 3) a medical record diagnosis of diabetes mellitus by a clinician on two or more occasions in the previous 10 years
• Definite or probable osteomyelitis in the diabetic foot, as defined by the International Working Group on the Diabetic Foot (Table 1). Criteria must be present at some point within 90 days prior to enrollment.
• All planned debridement has been completed prior to randomization.
• A course of backbone antimicrobial therapy has been selected.

You may not qualify if:

• Patient unable to receive enteral medication.
• Patient is allergic to or intolerant of rifampin.
• Patient is taking a drug that has interactions with rifampin that would require either stoppage, substitution or an empiric dose modification that may place the patient at medical risk.
• Within 30 days of enrollment, patient is taking immunosuppressive medications to prevent rejection of an organ transplant or is receiving chemotherapy for cancer or molecularly targeted therapies for cancer.
• Patient is receiving antiretroviral therapy for HIV or antiviral medication for Hepatitis C.
• Patient is participating in another interventional clinical trial for which a waiver of dual enrollment with CSP#2001 has not been obtained.
• Patient has an ALT \> 3 times the upper limit of normal for the site laboratory, or total bilirubin \> 2.5 times the upper limit of normal for the site laboratory\*,\*\*\*; INR \> 1.5, OR patient has Child-Pugh Class C Cirrhosis.
• Patient has a baseline white blood cell count (WBC) \<2000 cells/mm3\*\*\* OR absolute neutrophil count (ANC) \<1000 cells/mm3\*\*\* OR platelet count \<50,000 cells/mm3\*\*,\*\*\* OR hemoglobin \<8.0 g/dL.\*\*,\*\*\*.
• Women of child-bearing potential (those with menses within the last year) with a positive serum pregnancy test.
• Patient is believed unlikely to be able to complete the trial due to medical conditions.
• Patient is believed unlikely to complete the trial due to neurologic and psycho-behavioral disorders such as active substance abuse or dependence, disabling dementias or psychoses.
• Patient refuses or is clinically unable to undergo the recommended level of debridement.
• Indwelling hardware present in the foot, at the site of the index osteomyelitis.
• Treatment with antibacterial agents for infection at another site, where the duration of treatment is anticipated to be greater than 14 days.
• Patient is receiving therapy for COVID-19 that interacts with rifampin.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (30)

Phoenix VA Health Care System, Phoenix, AZ

Phoenix, Arizona, 85012, United States

Location

VA Loma Linda Healthcare System, Loma Linda, CA

Loma Linda, California, 92357-1000, United States

Location

VA Long Beach Healthcare System, Long Beach, CA

Long Beach, California, 90822, United States

Location

VA Palo Alto Health Care System, Palo Alto, CA

Palo Alto, California, 94304-1207, United States

Location

VA Northern California Health Care System, Mather, CA

Sacramento, California, 95655, United States

Location

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

West Los Angeles, California, 90073, United States

Location

Rocky Mountain Regional VA Medical Center, Aurora, CO

Aurora, Colorado, 80045-7211, United States

Location

Washington DC VA Medical Center, Washington, DC

Washington D.C., District of Columbia, 20422-0001, United States

Location

Bay Pines VA Healthcare System, Pay Pines, FL

Bay Pines, Florida, 33744-0000, United States

Location

North Florida/South Georgia Veterans Health System, Gainesville, FL

Gainesville, Florida, 32608-1135, United States

Location

Miami VA Healthcare System, Miami, FL

Miami, Florida, 33125, United States

Location

James A. Haley Veterans' Hospital, Tampa, FL

Tampa, Florida, 33612, United States

Location

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, 30033, United States

Location

VA Ann Arbor Healthcare System, Ann Arbor, MI

Ann Arbor, Michigan, 48105-2303, United States

Location

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, 55417, United States

Location

St. Louis VA Medical Center John Cochran Division, St. Louis, MO

St Louis, Missouri, 63106, United States

Location

James J. Peters VA Medical Center, Bronx, NY

The Bronx, New York, 10468-3904, United States

Location

Salisbury W.G. (Bill) Hefner VA Medical Center, Salisbury, NC

Salisbury, North Carolina, 28144, United States

Location

Cincinnati VA Medical Center, Cincinnati, OH

Cincinnati, Ohio, 45220, United States

Location

Louis Stokes VA Medical Center, Cleveland, OH

Cleveland, Ohio, 44106-1702, United States

Location

Dayton VA Medical Center, Dayton, OH

Dayton, Ohio, 45428, United States

Location

Oklahoma City VA Medical Center, Oklahoma City, OK

Oklahoma City, Oklahoma, 73104, United States

Location

VA Portland Health Care System, Portland, OR

Portland, Oregon, 97207-2964, United States

Location

Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

Nashville, Tennessee, 37212-2637, United States

Location

VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX

Dallas, Texas, 75216-7167, United States

Location

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, 77030, United States

Location

South Texas Health Care System, San Antonio, TX

San Antonio, Texas, 78229, United States

Location

VA Salt Lake City Health Care System, Salt Lake City, UT

Salt Lake City, Utah, 84148-0001, United States

Location

Salem VA Medical Center, Salem, VA

Salem, Virginia, 24153-6404, United States

Location

William S. Middleton Memorial Veterans Hospital, Madison, WI

Madison, Wisconsin, 53705-2254, United States

Location

Related Publications (1)

• Bessesen MT, Doros G, Henrie AM, Harrington KM, Hermos JA, Bonomo RA, Ferguson RE, Huang GD, Brown ST. A multicenter randomized placebo controlled trial of rifampin to reduce pedal amputations for osteomyelitis in veterans with diabetes (VA INTREPID). BMC Infect Dis. 2020 Jan 8;20(1):23. doi: 10.1186/s12879-019-4751-3.

  PMID: 31914940 DERIVED

MeSH Terms

Conditions

Osteomyelitis; Diabetes Mellitus

Interventions

Rifampin

Condition Hierarchy (Ancestors)

Bone Diseases, Infectious; Infections; Bone Diseases; Musculoskeletal Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Mary T Bessesen, MD

  Rocky Mountain Regional VA Medical Center, Aurora, CO

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2016
• First Posted: January 6, 2017
• Study Start: January 22, 2018
• Primary Completion: November 5, 2025
• Study Completion: November 5, 2025
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (30)