Clinical trial NCT00023348: TBTC Study 23A: Pharmacokinetics of Intermittent Isoniazid and Rifabutin in HIV-TB
Official title: TBTC Study 23A: Pharmacokinetics of Intermittent Isoniazid and Rifabutin in USPHS Study 23: Treatment of HIV-Related Tuberculosis Using a Rifabutin-Based Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: HIV Infections
Tuberculosis
Keywords: Tuberculosis
TB
Lead sponsor: Centers for Disease Control and Prevention
Sponsor class: FED
Collaborators: name: US Department of Veterans Affairs
First posted: 2001-09-10
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Primary Objectives:

1) To determine the proportion of patients with HIV-related tuberculosis who have abnormal pharmacokinetic parameters for isoniazid and rifabutin.

Secondary Objectives:

1. To determine risk factors for abnormal pharmacokinetic parameters for isoniazid and rifabutin.
2. To evaluate the correlation between pharmacokinetic parameters of isoniazid and rifabutin and the occurrence of toxicity attributed to antituberculous therapy.
3. To evaluate the correlation between pharmacokinetic parameters of isoniazid and rifabutin and the efficacy of TB therapy.
4. To define and correlate phenotypic INH acetylator status with the results of genotypic acetylator data obtained in the parent trial.

Detailed description: This study will seek to enroll every eligible patient enrolled in TBTC Study 23. Consenting patients will be asked to undergo measurements of isoniazid (if receiving), rifabutin and 25-OH desacetyl rifabutin levels at a time point in the study when steady state rifabutin levels are expected to have been achieved (at least two weeks following the start of rifabutin).

Eligibility criteria: Inclusion:

1. Patient enrolled in TBTC Study 23
2. Informed consent

Exclusion:

1. Severe anemia (Hct \<25%)

Primary outcomes:
measure: To determine the proportion of patients with HIV-related tuberculosis who have abnormal pharmacokinetics of isoniazid and rifabutin.
Secondary outcomes:
measure: 1) To determine risk factors for abnormal pharmacokinetics of isoniazid and rifabutin
measure: 2) To evaluate the correlation between pharmacokinetic parameters of isoniazid and rifabutin and the occurrence of toxicity attributed to antituberculous therapy.
measure: 3) To evaluate the correlation between pharmacokinetic parameters of isoniazid and rifabutin and the efficacy of TB therapy.
measure: 4) To define and correlate phenotypic INH acetylator status with the results of genotypic acetylator data obtained in the parent trial.
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Central Arkansas Veterans Health System
state: Arkansas
city: Los Angeles
country: United States
facility: LA County/USC Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Denver
country: United States
facility: Denver Department of Public Health and Hospitals
state: Colorado
city: Washington
country: United States
facility: Washington, D.C. VAMC
state: District of Columbia
city: Chicago
country: United States
facility: Chicago VA Medical Center (Lakeside)
state: Illinois
city: Hines
country: United States
facility: Hines VA Medical Center
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Newark
country: United States
facility: New Jersey Medical School
state: New Jersey
city: New York
country: United States
facility: New York University School of Medicine
state: New York
city: New York
country: United States
facility: Columbia University/Presbyterian Medical Center
state: New York
city: New York
country: United States
facility: Harlem Hospital Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Nashville
country: United States
facility: Nashville VA Medical Center
state: Tennessee
city: Fort Worth
country: United States
facility: University of North Texas Health Science Center
state: Texas
city: Houston
country: United States
facility: Thomas Street Clinic
state: Texas
city: San Antonio
country: United States
facility: Audi L. Murphy VA Hospital
state: Texas
city: Seattle
country: United States
facility: Seattle King County Health Department
state: Washington
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
city: Montreal
country: Canada
facility: Montreal Chest Institute McGill University
state: Quebec
Study officials:
affiliation: Audie L. Murphy VA Medical Center, San Antonio TX
name: Marc Weiner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Weiner M, Benator D, Burman W, Peloquin CA, Khan A, Vernon A, Jones B, Silva-Trigo C, Zhao Z, Hodge T; Tuberculosis Trials Consortium. Association between acquired rifamycin resistance and the pharmacokinetics of rifabutin and isoniazid among patients with HIV and tuberculosis. Clin Infect Dis. 2005 May 15;40(10):1481-91. doi: 10.1086/429321. Epub 2005 Apr 14.