Clinical trial NCT00000636: Prophylaxis Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculous Infection
Official title: Prophylaxis Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculous Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Tuberculosis
Keywords: Tuberculosis
Isoniazid
Pyrazinamide
Pyridoxine
Rifampin
AIDS-Related Opportunistic Infections
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
Antitubercular Agents
AIDS-Related Complex
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 2000
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate and compare the effectiveness of a 2-month regimen of rifampin and pyrazinamide versus a 1-year course of isoniazid (INH) to prevent the development of tuberculosis in patients who are coinfected with HIV and latent Mycobacterium tuberculosis (MTb).

Current guidelines recommend 6 to 12 months of treatment with INH for purified protein derivative (PPD)-positive individuals. Problems with this treatment include compliance, adverse reaction, and the possibility of not preventing disease due to INH-resistant organisms. Studies suggest that two or three months of rifampin and pyrazinamide may be more effective than longer courses of INH. A two-month prevention course should help to increase compliance. In addition, the use of two drugs (rifampin and pyrazinamide) may help overcome problems with drug resistance.

Detailed description: Current guidelines recommend 6 to 12 months of treatment with INH for purified protein derivative (PPD)-positive individuals. Problems with this treatment include compliance, adverse reaction, and the possibility of not preventing disease due to INH-resistant organisms. Studies suggest that two or three months of rifampin and pyrazinamide may be more effective than longer courses of INH. A two-month prevention course should help to increase compliance. In addition, the use of two drugs (rifampin and pyrazinamide) may help overcome problems with drug resistance.

After baseline screening, patients are randomized to one of two treatment arms and are evaluated by means of clinic visits monthly for the first three months, then every three months for the first year (there are additional clinic visits for INH patients). Patients are then evaluated every six months. One group of patients takes INH plus vitamin B6 for 12 months. The other group of patients takes 1 of 2 doses of rifampin (depending on patient's weight) plus pyrazinamide in 3-4 divided doses for 60 days.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Allowed:

* Antiretroviral treatment.
* Pneumocystis carinii pneumonia prophylaxis.
* Treatment for acute opportunistic infection/malignancy.
* Aminoglycosides, quinolones or fluoroquinolones such as ciprofloxacin or ofloxacin for \< 14 days for treatment of intercurrent infection.

Patients must have:

* HIV infection.
* Signed informed consent.
* Reasonably good health at time of study entry.
* Perceived life expectancy of at least six months.
* Allowed:
* Participation in other clinical trials as long as there is no potential activity of other study drugs against Mycobacterium tuberculosis (MTb), additive toxicities between study agents, or known possible drug interactions between study drugs.

Prior Medication:

Allowed:

* Treatment with quinolones, fluoroquinolones, aminoglycosides, or other agents with known or potential activity against M. tuberculosis.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

* Current active tuberculosis (confirmed or suspected).
* Sensitivity or intolerance to study medication.
* Acute hepatitis.
* Evidence of peripheral neuropathy, i.e., signs or symptoms of paresis, paresthesias, neuromotor abnormalities, or neurosensory deficits of grade 3 or worse.
* Inability to have concomitant medications changed to avoid serious interaction with study drug.

Concurrent Medication:

Excluded:

-

Quinolones, fluoroquinolones, or aminoglycosides with antituberculous activity (may be used for up to 14 days for treatment of intercurrent infection).Other agents with known or potential antituberculous activity should be avoided, including the following:

* Aminosalicylic acid salts, capreomycin, clofazimine, cycloserine, ethambutol, ethionamide, isoniazid, kanamycin, pyrazinamide, rifabutin, rifampin, streptomycin, and thiacetazone.

Prior Medication:

Excluded:

* History of treatment for \> 2 months with agents that have known or potential antituberculous activity other than those specifically allowed.

Agents with potential or known antituberculous activity include the following:

* Aminoglycosides such as amikacin, aminosalicylic acid salts, capreomycin, ciprofloxacin, clofazimine, cycloserine, ethambutol, ethionamide, isoniazid, kanamycin, ofloxacin, pyrazinamide, quinolones or fluoroquinolones, rifabutin, rifampin, streptomycin, and thiacetazone.

Patients may not have:

* Current active tuberculosis.
* Acute hepatitis.
* Peripheral neuropathy of grade 3 or grade 4.

Willing and able, in the clinician's opinion, to comply with the treatment and clinical management issues.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Community Consortium / UCSF
state: California
city: Denver
country: United States
facility: Denver CPCRA / Denver Public Hlth
state: Colorado
city: New Haven
country: United States
facility: Hill Health Corp
state: Connecticut
city: Wilmington
country: United States
facility: Wilmington Hosp / Med Ctr of Delaware
state: Delaware
city: Washington
country: United States
facility: Veterans Administration Med Ctr / Regional AIDS Program
state: District of Columbia
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Chicago Dept of Health / Speciality STD Clinic
state: Illinois
city: Chicago
country: United States
facility: AIDS Research Alliance - Chicago
state: Illinois
city: New Orleans
country: United States
facility: Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Univ / Brazil
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Univ / School of Hygiene & Public Health
state: Maryland
city: Boston
country: United States
facility: Boston Dept of Health and Hosps
state: Massachusetts
city: Detroit
country: United States
facility: Comprehensive AIDS Alliance of Detroit
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hosp
state: Michigan
city: Camden
country: United States
facility: Southern New Jersey AIDS Cln Trials / Dept of Med
state: New Jersey
city: Newark
country: United States
facility: Saint Michael's Med Ctr
state: New Jersey
city: Newark
country: United States
facility: Lattimore Comprehensive Pulmonary Disease Clinic
state: New Jersey
city: Newark
country: United States
facility: North Jersey Community Research Initiative
state: New Jersey
city: Bronx
country: United States
facility: Bronx Lebanon Hosp Ctr
state: New York
city: Brooklyn
country: United States
facility: Addiction Research and Treatment Corp
state: New York
city: New York
country: United States
facility: Clinical Directors Network of Region II
state: New York
city: New York
country: United States
facility: Beth Israel Med Ctr
state: New York
city: New York
country: United States
facility: Harlem AIDS Treatment Group / Harlem Hosp Ctr
state: New York
city: Philadelphia
country: United States
facility: Philadelphia FIGHT
state: Pennsylvania
city: Richmond
country: United States
facility: Richmond AIDS Consortium
state: Virginia
Study officials:
name: Gordin F
role: STUDY_CHAIR
name: Brown LS
role: STUDY_CHAIR
References:
citation: Gordin F, Matts J, Miller C, Chaisson R, Garcia M, O'Brien R. Risk factors for developing active tuberculosis (TB) among HIV-infected, PPD-positive (+) patients (pts). Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:151 (abstract no 448)
citation: New TB guidelines for persons with HIV. AIDS Treat News. 1998 Nov 6;(No 306):6.
citation: Gordin F, Chaisson RE, Matts JP, Miller C, de Lourdes Garcia M, Hafner R, Valdespino JL, Coberly J, Schechter M, Klukowicz AJ, Barry MA, O'Brien RJ. Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons: an international randomized trial. Terry Beirn Community Programs for Clinical Research on AIDS, the Adult AIDS Clinical Trials Group, the Pan American Health Organization, and the Centers for Disease Control and Prevention Study Group. JAMA. 2000 Mar 15;283(11):1445-50. doi: 10.1001/jama.283.11.1445.