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

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

Sponsors

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

Collaborator: Hoechst Marion Roussel
Lederle Laboratories

Source National Institute of Allergy and Infectious Diseases (NIAID)
Brief 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.

Detailed 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.

Overall Status Completed
Completion Date September 1999
Phase N/A
Study Type Interventional
Enrollment 2000
Condition
Intervention

Intervention Type: Drug

Intervention Name: Isoniazid

Intervention Type: Drug

Intervention Name: Pyrazinamide

Intervention Type: Drug

Intervention Name: Pyridoxine hydrochloride

Intervention Type: Drug

Intervention Name: Rifampin

Eligibility

Criteria:

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.

Gender: All

Minimum Age: 13 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role
Chaisson R Study Chair
Location
Facility:
Univ of Alabama at Birmingham | Birmingham, Alabama, 35294, United States
Children's Hosp of Los Angeles | Los Angeles, California, 90027, United States
Univ of Southern California / LA County USC Med Ctr | Los Angeles, California, 900331079, United States
Highland Gen Hosp / San Francisco Gen Hosp | Oakland, California, 946021018, United States
San Francisco Gen Hosp | San Francisco, California, 941102859, United States
Stanford at Kaiser / Kaiser Permanente Med Ctr | San Francisco, California, 94115, United States
Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium | San Jose, California, 951282699, United States
San Mateo AIDS Program / Stanford Univ | Stanford, California, 943055107, United States
Stanford Univ Med Ctr | Stanford, California, 943055107, United States
Olive View Med Ctr | Sylmar, California, 91342, United States
Harbor UCLA Med Ctr | Torrance, California, 90502, United States
Yale Univ / New Haven | New Haven, Connecticut, 065102483, United States
HIV Ctr - District of Columbia Gen Hosp | Washington, District of Columbia, 200072197, United States
Whitman - Walker Clinic / Georgetown Univ Med Ctr | Washington, District of Columbia, 200072197, United States
Georgetown Univ Med Ctr | Washington, District of Columbia, 20007, United States
Howard Univ | Washington, District of Columbia, 20059, United States
Univ of Miami School of Medicine | Miami, Florida, 331361013, United States
Queens Med Ctr | Honolulu, Hawaii, 96816, United States
Univ of Hawaii | Honolulu, Hawaii, 96816, United States
Children's Mem Hosp Family Cln / Northwestern Univ Med Schl | Chicago, Illinois, 60611, United States
Northwestern Univ Med School | Chicago, Illinois, 60611, United States
Rush Presbyterian - Saint Luke's Med Ctr | Chicago, Illinois, 60612, United States
Louis A Weiss Memorial Hosp | Chicago, Illinois, 60640, United States
Indiana Univ Hosp | Indianapolis, Indiana, 462025250, United States
State of MD Div of Corrections / Johns Hopkins Univ Hosp | Baltimore, Maryland, 212052196, United States
Johns Hopkins Hosp | Baltimore, Maryland, 21287, United States
Beth Israel Deaconess - West Campus | Boston, Massachusetts, 02215, United States
Baystate Med Ctr of Springfield | Springfield, Massachusetts, 01199, United States
St Louis Regional Hosp / St Louis Regional Med Ctr | St Louis, Missouri, 63112, United States
Univ of Nebraska Med Ctr | Omaha, Nebraska, 681985130, United States
Univ of Medicine & Dentistry of New Jersey / Univ Hosp | Newark, New Jersey, 071032714, United States
Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl | Newark, New Jersey, 071072198, United States
Adirondack Med Ctr at Saranac Lake | Albany, New York, 122083479, United States
Albany Med College / Division of HIV Medicine A158 | Albany, New York, 122083479, United States
Mid - Hudson Care Ctr | Albany, New York, 122083479, United States
Bronx Municipal Hosp Ctr/Jacobi Med Ctr | Bronx, New York, 10461, United States
Comprehensive Health Care Ctr / Bronx Municipal Hosp | Bronx, New York, 10461, United States
Montefiore Drug Treatment Ctr / Bronx Municipal Hosp | Bronx, New York, 10461, United States
Montefiore Family Health Ctr / Bronx Municipal Hosp | Bronx, New York, 10461, United States
Samaritan Village Inc / Bronx Municipal Hosp | Bronx, New York, 10461, United States
Jack Weiler Hosp / Bronx Municipal Hosp | Bronx, New York, 10465, United States
Montefiore Med Ctr / Bronx Municipal Hosp | Bronx, New York, 10467, United States
Montefiore Med Ctr Adolescent AIDS Program | Bronx, New York, 10467, United States
North Central Bronx Hosp / Bronx Municipal Hosp | Bronx, New York, 10467, United States
Interfaith Med Ctr | Brooklyn, New York, 112032098, United States
SUNY / Health Sciences Ctr at Brooklyn | Brooklyn, New York, 112032098, United States
SUNY / Erie County Med Ctr at Buffalo | Buffalo, New York, 14215, United States
Nassau County Med Ctr | East Meadow, New York, 11554, United States
City Hosp Ctr at Elmhurst / Mount Sinai Hosp | Elmhurst, New York, 11373, United States
North Shore Univ Hosp | Manhasset, New York, 11030, United States
Beth Israel Med Ctr | New York, New York, 10003, United States
Bellevue Hosp / New York Univ Med Ctr | New York, New York, 10016, United States
Saint Clare's Hosp and Health Ctr | New York, New York, 10019, United States
Cornell Univ Med Ctr | New York, New York, 10021, United States
Saint Luke's - Roosevelt Hosp Ctr | New York, New York, 10025, United States
Mount Sinai Med Ctr | New York, New York, 10029, United States
Columbia Presbyterian Med Ctr | New York, New York, 100323784, United States
SUNY - Stony Brook | Stony Brook, New York, 117948153, United States
SUNY / State Univ of New York | Syracuse, New York, 13210, United States
Univ of North Carolina | Chapel Hill, North Carolina, 275997215, United States
Moses H Cone Memorial Hosp | Greensboro, North Carolina, 27401, United States
Wake County Dept of Health | Raleigh, North Carolina, 27610, United States
Univ of Cincinnati | Cincinnati, Ohio, 452670405, United States
Univ of Kentucky Lexington | Cincinnati, Ohio, 45267, United States
Case Western Reserve Univ | Cleveland, Ohio, 44106, United States
MetroHealth Med Ctr | Cleveland, Ohio, 441091998, United States
Ohio State Univ Hosp Clinic | Columbus, Ohio, 432101228, United States
Girard Med Ctr | Philadelphia, Pennsylvania, 191046073, United States
Univ of Pennsylvania at Philadelphia | Philadelphia, Pennsylvania, 19104, United States
Thomas Jefferson Univ Hosp | Philadelphia, Pennsylvania, 191075098, United States
Med Univ of South Carolina / UNC | Charleston, South Carolina, 29425, United States
Julio Arroyo | West Columbia, South Carolina, 29169, United States
Meharry Med College | Nashville, Tennessee, 37203, United States
Univ of Texas Galveston | Galveston, Texas, 775550435, United States
Houston Clinical Research Network | Houston, Texas, 77266, United States
Univ of Puerto Rico | San Juan, 009365067, Puerto Rico
Location Countries

Puerto Rico

United States

Verification Date

March 2012

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Study Design Info

Intervention Model: Parallel Assignment

Primary Purpose: Prevention

Source: ClinicalTrials.gov