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Preventive Treatment 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
NCT00000638
Collaborator
Hoechst Marion Roussel (Industry), Lederle Laboratories (Industry)
2,000
Enrollment
76
Locations
26.3
Patients Per Site

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
N/A

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.

Study Design

Study Type:
Interventional
Intervention Model:
Parallel Assignment
Primary Purpose:
Prevention
Official Title:
Prophylaxis Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculous Infection
Actual Study Completion Date :
Sep 1, 1999

Outcome Measures

Primary Outcome Measures

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    13 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Univ of Alabama at Birmingham Birmingham Alabama United States 35294
    2 Children's Hosp of Los Angeles Los Angeles California United States 90027
    3 Univ of Southern California / LA County USC Med Ctr Los Angeles California United States 900331079
    4 Highland Gen Hosp / San Francisco Gen Hosp Oakland California United States 946021018
    5 San Francisco Gen Hosp San Francisco California United States 941102859
    6 Stanford at Kaiser / Kaiser Permanente Med Ctr San Francisco California United States 94115
    7 Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium San Jose California United States 951282699
    8 San Mateo AIDS Program / Stanford Univ Stanford California United States 943055107
    9 Stanford Univ Med Ctr Stanford California United States 943055107
    10 Olive View Med Ctr Sylmar California United States 91342
    11 Harbor UCLA Med Ctr Torrance California United States 90502
    12 Yale Univ / New Haven New Haven Connecticut United States 065102483
    13 HIV Ctr - District of Columbia Gen Hosp Washington District of Columbia United States 200072197
    14 Whitman - Walker Clinic / Georgetown Univ Med Ctr Washington District of Columbia United States 200072197
    15 Georgetown Univ Med Ctr Washington District of Columbia United States 20007
    16 Howard Univ Washington District of Columbia United States 20059
    17 Univ of Miami School of Medicine Miami Florida United States 331361013
    18 Queens Med Ctr Honolulu Hawaii United States 96816
    19 Univ of Hawaii Honolulu Hawaii United States 96816
    20 Children's Mem Hosp Family Cln / Northwestern Univ Med Schl Chicago Illinois United States 60611
    21 Northwestern Univ Med School Chicago Illinois United States 60611
    22 Rush Presbyterian - Saint Luke's Med Ctr Chicago Illinois United States 60612
    23 Louis A Weiss Memorial Hosp Chicago Illinois United States 60640
    24 Indiana Univ Hosp Indianapolis Indiana United States 462025250
    25 State of MD Div of Corrections / Johns Hopkins Univ Hosp Baltimore Maryland United States 212052196
    26 Johns Hopkins Hosp Baltimore Maryland United States 21287
    27 Beth Israel Deaconess - West Campus Boston Massachusetts United States 02215
    28 Baystate Med Ctr of Springfield Springfield Massachusetts United States 01199
    29 St Louis Regional Hosp / St Louis Regional Med Ctr Saint Louis Missouri United States 63112
    30 Univ of Nebraska Med Ctr Omaha Nebraska United States 681985130
    31 Univ of Medicine & Dentistry of New Jersey / Univ Hosp Newark New Jersey United States 071032714
    32 Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl Newark New Jersey United States 071072198
    33 Adirondack Med Ctr at Saranac Lake Albany New York United States 122083479
    34 Albany Med College / Division of HIV Medicine A158 Albany New York United States 122083479
    35 Mid - Hudson Care Ctr Albany New York United States 122083479
    36 Bronx Municipal Hosp Ctr/Jacobi Med Ctr Bronx New York United States 10461
    37 Comprehensive Health Care Ctr / Bronx Municipal Hosp Bronx New York United States 10461
    38 Montefiore Drug Treatment Ctr / Bronx Municipal Hosp Bronx New York United States 10461
    39 Montefiore Family Health Ctr / Bronx Municipal Hosp Bronx New York United States 10461
    40 Samaritan Village Inc / Bronx Municipal Hosp Bronx New York United States 10461
    41 Jack Weiler Hosp / Bronx Municipal Hosp Bronx New York United States 10465
    42 Montefiore Med Ctr / Bronx Municipal Hosp Bronx New York United States 10467
    43 Montefiore Med Ctr Adolescent AIDS Program Bronx New York United States 10467
    44 North Central Bronx Hosp / Bronx Municipal Hosp Bronx New York United States 10467
    45 Interfaith Med Ctr Brooklyn New York United States 112032098
    46 SUNY / Health Sciences Ctr at Brooklyn Brooklyn New York United States 112032098
    47 SUNY / Erie County Med Ctr at Buffalo Buffalo New York United States 14215
    48 Nassau County Med Ctr East Meadow New York United States 11554
    49 City Hosp Ctr at Elmhurst / Mount Sinai Hosp Elmhurst New York United States 11373
    50 North Shore Univ Hosp Manhasset New York United States 11030
    51 Beth Israel Med Ctr New York New York United States 10003
    52 Bellevue Hosp / New York Univ Med Ctr New York New York United States 10016
    53 Saint Clare's Hosp and Health Ctr New York New York United States 10019
    54 Cornell Univ Med Ctr New York New York United States 10021
    55 Saint Luke's - Roosevelt Hosp Ctr New York New York United States 10025
    56 Mount Sinai Med Ctr New York New York United States 10029
    57 Columbia Presbyterian Med Ctr New York New York United States 100323784
    58 SUNY - Stony Brook Stony Brook New York United States 117948153
    59 SUNY / State Univ of New York Syracuse New York United States 13210
    60 Univ of North Carolina Chapel Hill North Carolina United States 275997215
    61 Moses H Cone Memorial Hosp Greensboro North Carolina United States 27401
    62 Wake County Dept of Health Raleigh North Carolina United States 27610
    63 Univ of Cincinnati Cincinnati Ohio United States 452670405
    64 Univ of Kentucky Lexington Cincinnati Ohio United States 45267
    65 Case Western Reserve Univ Cleveland Ohio United States 44106
    66 MetroHealth Med Ctr Cleveland Ohio United States 441091998
    67 Ohio State Univ Hosp Clinic Columbus Ohio United States 432101228
    68 Girard Med Ctr Philadelphia Pennsylvania United States 191046073
    69 Univ of Pennsylvania at Philadelphia Philadelphia Pennsylvania United States 19104
    70 Thomas Jefferson Univ Hosp Philadelphia Pennsylvania United States 191075098
    71 Med Univ of South Carolina / UNC Charleston South Carolina United States 29425
    72 Julio Arroyo West Columbia South Carolina United States 29169
    73 Meharry Med College Nashville Tennessee United States 37203
    74 Univ of Texas Galveston Galveston Texas United States 775550435
    75 Houston Clinical Research Network Houston Texas United States 77266
    76 Univ of Puerto Rico San Juan Puerto Rico 009365067

    Sponsors and Collaborators

    • National Institute of Allergy and Infectious Diseases (NIAID)
    • Hoechst Marion Roussel
    • Lederle Laboratories

    Investigators

    • Study Chair: Chaisson R,

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    National Institute of Allergy and Infectious Diseases (NIAID)
    ClinicalTrials.gov Identifier:
    NCT00000638
    Other Study ID Numbers:
    • ACTG 177
    • CPCRA 004
    • TB/PPD+
    • 11152
    First Posted:
    Aug 31, 2001
    Last Update Posted:
    Nov 2, 2021
    Last Verified:
    Oct 1, 2021
    Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID)
    Tuberculosis
    Isoniazid
    Mycobacterium tuberculosis
    Pyrazinamide
    Pyridoxine
    Rifampin
    AIDS-Related Opportunistic Infections
    Drug Therapy, Combination
    Acquired Immunodeficiency Syndrome
    Antitubercular Agents
    AIDS-Related Complex
    Additional relevant MeSH terms:
    Infections
    Communicable Diseases
    HIV Infections
    Tuberculosis
    Acquired Immunodeficiency Syndrome
    Immunologic Deficiency Syndromes
    Pyridoxine
    Vitamin B 6
    Rifampin
    Isoniazid
    Pyrazinamide

    Study Results

    No Results Posted as of Nov 2, 2021