Preventive Treatment 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: NCT00000638
• Other study ID #: ACTG 177
• Secondary ID: CPCRA 004TB/PPD+
• Status: Completed
• Phase: N/A
• Est. completion date: September 1999

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 safety and effectiveness of a one-year course of isoniazid (INH) versus a two-month course of rifampin plus pyrazinamide for the prevention of reactivation tuberculosis in individuals infected with both HIV and latent (inactive) Mycobacterium tuberculosis.

Current guidelines from the American Thoracic Society and the Centers for Disease Control recommend 6 to 12 months of INH for PPD (purified protein derivative)-positive individuals. Although the effectiveness of this treatment is not known for HIV-infected individuals, several studies using INH to prevent tuberculosis in presumably normal hosts have shown 60 to 80 percent effectiveness. Problems with this treatment include compliance, adverse reaction, and the possibility of not preventing disease due to tuberculosis organisms being resistant to INH. A two-month preventive treatment plan should help in increasing compliance. In addition, the use of two drugs (rifampin / pyrazinamide) may help overcome problems with drug resistance. If this study shows equal or greater effectiveness of the two-month rifampin / pyrazinamide treatment, it could alter the approach to tuberculosis prevention for both HIV-positive and HIV-negative individuals.

Description:

Current guidelines from the American Thoracic Society and the Centers for Disease Control recommend 6 to 12 months of INH for PPD (purified protein derivative)-positive individuals. Although the effectiveness of this treatment is not known for HIV-infected individuals, several studies using INH to prevent tuberculosis in presumably normal hosts have shown 60 to 80 percent effectiveness. Problems with this treatment include compliance, adverse reaction, and the possibility of not preventing disease due to tuberculosis organisms being resistant to INH. A two-month preventive treatment plan should help in increasing compliance. In addition, the use of two drugs (rifampin / pyrazinamide) may help overcome problems with drug resistance. If this study shows equal or greater effectiveness of the two-month rifampin / pyrazinamide treatment, it could alter the approach to tuberculosis prevention for both HIV-positive and HIV-negative individuals.

Patients are chosen by a random selection process to either the INH or the rifampin / pyrazinamide arm of the dose. Patients on the INH arm receive INH plus vitamin B6 (pyridoxine hydrochloride ) daily for 12 months. Patients on the other arm receive rifampin plus pyrazinamide for 60 days. Dosage of rifampin and pyrazinamide depends on weight of patient.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2000
• Est. completion date: September 1999
• 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.

Patients must have:

• HIV infection.

• Current or documented history of positive PPD skin test.

• Life expectancy of at least 6 months or, in the physician's opinion, patient has a reasonable chance of survival to end of study.

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.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Current active clinical tuberculosis, confirmed or suspected.

• History of sensitivity / intolerance to any study medication.

• Evidence of peripheral neuropathy, i.e., signs or symptoms of paresis, paresthesias, neuromotor abnormalities, or neurosensory deficits of grade 3 or worse.

• Unwilling or unable to have current therapy and/or concomitant medication changed to avoid serious interaction with study medication.

• Acute hepatitis.

• Unable to comply with the follow-up requirements of the protocol.

Concurrent Medication:

Excluded:

• Treatment with quinolones, fluoroquinolones, aminoglycosides, or other agents that have activity against Mycobacterium tuberculosis.

• Excluded as ongoing (i.e., continuous, chronic and/or recurring) treatment:

• Aminoglycosides such as amikacin, aminosalicylic acid salts (PAS), capreomycin, clofazimine, cycloserine, ethambutol, ethionamide, isoniazid (INH) if randomized to rifampin/pyrazinamide arm of study, kanamycin, pyrazinamide if randomized to INH arm of study, and quinolones and fluoroquinolones, i.e., rifabutin, rifampin (if randomized to INH arm of study), ciprofloxacin, levofloxacin, ofloxacin, streptomycin, and thiacetazone.

Prior Medication:

Excluded:

• More than 2 months of continuous treatment, after documentation of a positive PPD skin test, with agents that have known or potential antituberculous activity or any antimycobacterial medication for > 1 month.

Patients may not have the following prior conditions:

• History of sensitivity / intolerance to any study medication.

• Unwilling or unable to comply with the follow-up requirements of the protocol.

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
Puerto Rico	Univ of Puerto Rico	San Juan
United States	Adirondack Med Ctr at Saranac Lake	Albany	New York
United States	Albany Med College / Division of HIV Medicine A158	Albany	New York
United States	Mid - Hudson Care Ctr	Albany	New York
United States	Johns Hopkins Hosp	Baltimore	Maryland
United States	State of MD Div of Corrections / Johns Hopkins Univ Hosp	Baltimore	Maryland
United States	Univ of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess - West Campus	Boston	Massachusetts
United States	Bronx Municipal Hosp Ctr/Jacobi Med Ctr	Bronx	New York
United States	Comprehensive Health Care Ctr / Bronx Municipal Hosp	Bronx	New York
United States	Jack Weiler Hosp / Bronx Municipal Hosp	Bronx	New York
United States	Montefiore Drug Treatment Ctr / Bronx Municipal Hosp	Bronx	New York
United States	Montefiore Family Health Ctr / Bronx Municipal Hosp	Bronx	New York
United States	Montefiore Med Ctr / Bronx Municipal Hosp	Bronx	New York
United States	Montefiore Med Ctr Adolescent AIDS Program	Bronx	New York
United States	North Central Bronx Hosp / Bronx Municipal Hosp	Bronx	New York
United States	Samaritan Village Inc / Bronx Municipal Hosp	Bronx	New York
United States	Interfaith Med Ctr	Brooklyn	New York
United States	SUNY / Health Sciences Ctr at Brooklyn	Brooklyn	New York
United States	SUNY / Erie County Med Ctr at Buffalo	Buffalo	New York
United States	Univ of North Carolina	Chapel Hill	North Carolina
United States	Med Univ of South Carolina / UNC	Charleston	South Carolina
United States	Children's Mem Hosp Family Cln / Northwestern Univ Med Schl	Chicago	Illinois
United States	Louis A Weiss Memorial Hosp	Chicago	Illinois
United States	Northwestern Univ Med School	Chicago	Illinois
United States	Rush Presbyterian - Saint Luke's Med Ctr	Chicago	Illinois
United States	Univ of Cincinnati	Cincinnati	Ohio
United States	Univ of Kentucky Lexington	Cincinnati	Ohio
United States	Case Western Reserve Univ	Cleveland	Ohio
United States	MetroHealth Med Ctr	Cleveland	Ohio
United States	Ohio State Univ Hosp Clinic	Columbus	Ohio
United States	Nassau County Med Ctr	East Meadow	New York
United States	City Hosp Ctr at Elmhurst / Mount Sinai Hosp	Elmhurst	New York
United States	Univ of Texas Galveston	Galveston	Texas
United States	Moses H Cone Memorial Hosp	Greensboro	North Carolina
United States	Queens Med Ctr	Honolulu	Hawaii
United States	Univ of Hawaii	Honolulu	Hawaii
United States	Houston Clinical Research Network	Houston	Texas
United States	Indiana Univ Hosp	Indianapolis	Indiana
United States	Children's Hosp of Los Angeles	Los Angeles	California
United States	Univ of Southern California / LA County USC Med Ctr	Los Angeles	California
United States	North Shore Univ Hosp	Manhasset	New York
United States	Univ of Miami School of Medicine	Miami	Florida
United States	Meharry Med College	Nashville	Tennessee
United States	Yale Univ / New Haven	New Haven	Connecticut
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Beth Israel Med Ctr	New York	New York
United States	Columbia Presbyterian Med Ctr	New York	New York
United States	Cornell Univ Med Ctr	New York	New York
United States	Mount Sinai Med Ctr	New York	New York
United States	Saint Clare's Hosp and Health Ctr	New York	New York
United States	Saint Luke's - Roosevelt Hosp Ctr	New York	New York
United States	Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl	Newark	New Jersey
United States	Univ of Medicine & Dentistry of New Jersey / Univ Hosp	Newark	New Jersey
United States	Highland Gen Hosp / San Francisco Gen Hosp	Oakland	California
United States	Univ of Nebraska Med Ctr	Omaha	Nebraska
United States	Girard Med Ctr	Philadelphia	Pennsylvania
United States	Thomas Jefferson Univ Hosp	Philadelphia	Pennsylvania
United States	Univ of Pennsylvania at Philadelphia	Philadelphia	Pennsylvania
United States	Wake County Dept of Health	Raleigh	North Carolina
United States	St Louis Regional Hosp / St Louis Regional Med Ctr	Saint Louis	Missouri
United States	San Francisco Gen Hosp	San Francisco	California
United States	Stanford at Kaiser / Kaiser Permanente Med Ctr	San Francisco	California
United States	Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium	San Jose	California
United States	Baystate Med Ctr of Springfield	Springfield	Massachusetts
United States	San Mateo AIDS Program / Stanford Univ	Stanford	California
United States	Stanford Univ Med Ctr	Stanford	California
United States	SUNY - Stony Brook	Stony Brook	New York
United States	Olive View Med Ctr	Sylmar	California
United States	SUNY / State Univ of New York	Syracuse	New York
United States	Harbor UCLA Med Ctr	Torrance	California
United States	Georgetown Univ Med Ctr	Washington	District of Columbia
United States	HIV Ctr - District of Columbia Gen Hosp	Washington	District of Columbia
United States	Howard Univ	Washington	District of Columbia
United States	Whitman - Walker Clinic / Georgetown Univ Med Ctr	Washington	District of Columbia
United States	Julio Arroyo	West Columbia	South Carolina

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Hoechst Marion Roussel, Lederle Laboratories

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (2)

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

Halsey N, et al. Twice weekly INH vs RIF and PZA for TB prophylaxis in HIV infected adults. Natl Conf Hum Retroviruses Relat Infect (2nd). 1995 Jan 29-Feb 2:55