Rifabutin Based Therapy for the Eradication of Staphylococcus Aureus Colonization in HIV Infected Adults

NCT00869518 | Terminated Phase 2 Results

• 1 other identifier: 08033578
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

DESIGN: This single center, double-blinded, randomized phase II study is being conducted to assess the efficacy of a rifabutin based regimen to eliminate S. aureus colonization in HIV infected individuals. Individuals must have HIV infection and a skin and skin structure infection (SSSI) in the prior 6 months to be eligible for screening. Prior to enrollment, subjects will be cultured for evidence of S. aureus colonization. Individuals who are culture positive at ≥ one body site will be eligible for enrollment. Subjects who meet inclusion and exclusion criteria and consent to participate in the study will be randomized to seven days of rifabutin plus trimethoprim-sulfamethoxazole (TMP-SMX) or TMP-SMX alone. Following completion of treatment subjects will be screened seven days, 30 days, and 60 days post-treatment for colonization at multiple body-sites. Subjects will also be actively followed for evidence of SSSI. SUBJECT PARTICIPATION DURATION: 12 weeks SAMPLE SIZE: 88 total subjects POPULATION: 200 HIV infected individuals who receive care at San Francisco General Hospital HIV clinic (Ward 86) with a history of SSSI in the prior 6 months will be screened for S. aureus colonization. DESCRIPTION OF AGENT OR INTERVENTION: This is a double-blind trial comparing rifabutin plus TMP-SMX versus placebo plus TMP-SMX. Placebo will be administered at a dose of 300 mg p.o. daily or an equivalent dose depending on co-administration of other drugs that may adjust the serum level of rifabutin. TMP-SMX will be administered at a dose of trimethoprim 160 mg and sulfamethoxazole 800 mg p.o. twice daily or adjusted per CrCl. Study drug will be provided by the study and administered for 7 days.

Conditions

Staphylococcus Aureus; HIV Infections

Keywords

Staphylococcus aureus; colonization; eradication; HIV; rifabutin

Outcome Measures

Primary Outcomes (1)

• Eradication of S. Aureus Colonization

  Eradication was measured by performing cultures for S aureus at the nose, throat, and groin

  30 days following completion of treatment

Secondary Outcomes (3)

• Eradication of S. Aureus Colonization

  7 days following completion of treatment

• Eradication of S. Aureus Colonization

  60 days following completion of treatment

• Recurrent Skin and Skin Structure Infections (SSTI)

  up to 30 days following completion of treatment

Study Arms (2)

Rifabutin

ACTIVE COMPARATOR

Subjects will be assigned to 7 days of treatment with rifabutin plus trimethoprim-sulfamethoxazole

Drug: rifabutin plus trimethoprim sulfamethoxazole

Placebo

PLACEBO COMPARATOR

Subjects will be assigned to 7 days of treatment with placebo plus trimethoprim-sulfamethoxazole

Drug: placebo plus trimethoprim-sulfamethoxazole

Interventions

rifabutin plus trimethoprim sulfamethoxazole DRUG

rifabutin 300 mg PO daily or equivalent depending on concomitant medications plus trimethoprim-sulfamethoxazole 1 DS tab twice daily both for 7 days

Rifabutin

placebo plus trimethoprim-sulfamethoxazole DRUG

placebo plus trimethoprim-sulfamethoxazole 1 DS tab twice daily both for 7 days

Placebo

Eligibility Criteria

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

You may qualify if:

• Age \> 18 years
• HIV infection as reported by the subject's physician
• Physician-reported SSSI within the prior 6 months.
• S. aureus colonization at ≥ 1 body site as defined as a positive culture for S. aureus at minimum one of five cultures taken at pre-enrollment screening.
• Subjects (or their legally acceptable representatives) must have signed an informed consent documentation indicating that they understand the purpose of and procedures required for the study, and are willing to participate in the study

You may not qualify if:

• Female subjects who are pregnant or lactating.
• Known or suspected hypersensitivity to rifabutin, a rifamycin class antimicrobial, TMP-SMX or another sulfa based medication.
• Known or suspected condition or concurrent treatment that would be contraindicated by the prescribing of rifabutin or TMP-SMX.
• Receipt of an anti-staphylococcal antimicrobial within 14 days prior to administration of study drug (TMP-SMX, clindamycin, any macrolide, any tetracycline, any rifamycin, any fluoroquinolone, vancomycin, linezolid, daptomycin, any penicillin, any carbapenem, or any cephalosporin).
• Diagnosis of an active SSSI or other signs and symptoms of S. aureus infection at the time of study enrollment
• Physician-reported diagnosis of active or untreated latent mycobacterial infection
• CrCl \< 30 ml/min as determined by the Cockcroft-Gault Method using a serum creatinine from a value obtained within the last 6 months.
• No serum creatinine value available for the subject in the SFGH clinical laboratory system (LCR) within 6 months prior to enrollment.
• Physician-reported diagnosis of end-stage liver disease
• Physician-reported diagnosis of uveitis in the past or at time of enrollment
• Concomitant use of medications with unknown pharmacokinetic interactions with rifabutin or contraindicated with rifabutin (unboosted indinavir, unboosted saquinavir, delavirdine, atovaquone, azithromycin, Bacillus of Calmette and Guerin \[only if recent administration for bladder cancer treatment\], dapsone, dasatinib, erlotininb, ethinyl estradiol, fluconazole, imatinab, itinotecan, itraconazole, ixabepilone, lapatinib, levonorgestrel, mestranol, nilotininb, norelgestromin, norethindrone, posaconazole, ranolazine, sirolimus, sunitinib, tacrolimus, temsirolimus, trimetrexate, voriconazole, warfarin)
• Colonizing S. aureus isolate resistant to TMP-SMX
• Colonizing S. aureus isolate resistant to rifampin (rifampin resistance will serve as a surrogate for rifabutin resistance at initial screening)
• Subjects who are unlikely to be able to comply with the mandated study visits

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

San Francisco General Hospital

San Francisco, California, 94110, United States

Location

MeSH Terms

Conditions

Staphylococcal Infections; HIV Infections

Interventions

Rifabutin; Trimethoprim, Sulfamethoxazole Drug Combination

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Brian S. Schwartz, MD
• Organization: University of California, San Francisco

brian.schwartz@ucsf.edu

415-476-5767

Study Officials

• Henry F Chambers, MD

  University of Califronia, San Francisco

  PRINCIPAL INVESTIGATOR

• Brian S Schwartz, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2009
• First Posted: March 26, 2009
• Study Start: July 1, 2009
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: May 14, 2014
• Results First Posted: April 21, 2014

Record last verified: 2014-04

Locations

US (1)