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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000636
• Other study ID #: CPCRA 004
• Secondary ID: TB/PPD+ACTG 1771
• Status: Completed
• Phase: N/A
• Est. completion date: October 1997

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2000
• Est. completion date: October 1997
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• HIV Infections
• Immunologic Deficiency Syndromes
• Infections
• Tuberculosis

Intervention

Drug:
• Isoniazid

• Pyrazinamide

• Pyridoxine hydrochloride

• Rifampin

Locations

Country	Name	City	State
United States	AIDS Research Consortium of Atlanta	Atlanta	Georgia
United States	Johns Hopkins Univ / Brazil	Baltimore	Maryland
United States	Johns Hopkins Univ / School of Hygiene & Public Health	Baltimore	Maryland
United States	Boston Dept of Health and Hosps	Boston	Massachusetts
United States	Bronx Lebanon Hosp Ctr	Bronx	New York
United States	Addiction Research and Treatment Corp	Brooklyn	New York
United States	Southern New Jersey AIDS Cln Trials / Dept of Med	Camden	New Jersey
United States	AIDS Research Alliance - Chicago	Chicago	Illinois
United States	Chicago Dept of Health / Speciality STD Clinic	Chicago	Illinois
United States	Denver CPCRA / Denver Public Hlth	Denver	Colorado
United States	Comprehensive AIDS Alliance of Detroit	Detroit	Michigan
United States	Henry Ford Hosp	Detroit	Michigan
United States	Hill Health Corp	New Haven	Connecticut
United States	Louisiana Comm AIDS Rsch Prog / Tulane Univ Med	New Orleans	Louisiana
United States	Beth Israel Med Ctr	New York	New York
United States	Clinical Directors Network of Region II	New York	New York
United States	Harlem AIDS Treatment Group / Harlem Hosp Ctr	New York	New York
United States	Lattimore Comprehensive Pulmonary Disease Clinic	Newark	New Jersey
United States	North Jersey Community Research Initiative	Newark	New Jersey
United States	Saint Michael's Med Ctr	Newark	New Jersey
United States	Philadelphia FIGHT	Philadelphia	Pennsylvania
United States	Richmond AIDS Consortium	Richmond	Virginia
United States	Community Consortium / UCSF	San Francisco	California
United States	Veterans Administration Med Ctr / Regional AIDS Program	Washington	District of Columbia
United States	Wilmington Hosp / Med Ctr of Delaware	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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)

New TB guidelines for persons with HIV. AIDS Treat News. 1998 Nov 6;(No 306):6. — View Citation