Prophylaxis Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculous Infection

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000636

Collaborator

(none)

2,000

Enrollment

Locations

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections Tuberculosis	Drug: Isoniazid Drug: Pyrazinamide Drug: Pyridoxine hydrochloride Drug: Rifampin	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Intervention Model:

Parallel Assignment

Primary Purpose:

Treatment

Official Title:

Prophylaxis Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculous Infection

Actual Study Completion Date :

Oct 1, 1997

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Community Consortium / UCSF	San Francisco	California	United States	94110
2	Denver CPCRA / Denver Public Hlth	Denver	Colorado	United States	802044507
3	Hill Health Corp	New Haven	Connecticut	United States	06519
4	Wilmington Hosp / Med Ctr of Delaware	Wilmington	Delaware	United States	19899
5	Veterans Administration Med Ctr / Regional AIDS Program	Washington	District of Columbia	United States	20422
6	AIDS Research Consortium of Atlanta	Atlanta	Georgia	United States	30308
7	Chicago Dept of Health / Speciality STD Clinic	Chicago	Illinois	United States	60605
8	AIDS Research Alliance - Chicago	Chicago	Illinois	United States	60657
9	Louisiana Comm AIDS Rsch Prog / Tulane Univ Med	New Orleans	Louisiana	United States	70112
10	Johns Hopkins Univ / Brazil	Baltimore	Maryland	United States	21205
11	Johns Hopkins Univ / School of Hygiene & Public Health	Baltimore	Maryland	United States	21205
12	Boston Dept of Health and Hosps	Boston	Massachusetts	United States	02118
13	Comprehensive AIDS Alliance of Detroit	Detroit	Michigan	United States	48201
14	Henry Ford Hosp	Detroit	Michigan	United States	48202
15	Southern New Jersey AIDS Cln Trials / Dept of Med	Camden	New Jersey	United States	08103
16	Saint Michael's Med Ctr	Newark	New Jersey	United States	07102
17	Lattimore Comprehensive Pulmonary Disease Clinic	Newark	New Jersey	United States	07103
18	North Jersey Community Research Initiative	Newark	New Jersey	United States	07103
19	Bronx Lebanon Hosp Ctr	Bronx	New York	United States	10456
20	Addiction Research and Treatment Corp	Brooklyn	New York	United States	11201
21	Clinical Directors Network of Region II	New York	New York	United States	10011
22	Beth Israel Med Ctr	New York	New York	United States	10035
23	Harlem AIDS Treatment Group / Harlem Hosp Ctr	New York	New York	United States	10037
24	Philadelphia FIGHT	Philadelphia	Pennsylvania	United States	19107
25	Richmond AIDS Consortium	Richmond	Virginia	United States	23298