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

This study has been completed.
Sponsor:
Collaborators:
Hoechst Marion Roussel
Lederle Laboratories
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000638
First received: November 2, 1999
Last updated: March 29, 2012
Last verified: March 2012
  Purpose

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 Intervention
HIV Infections
Tuberculosis
Drug: Isoniazid
Drug: Pyrazinamide
Drug: Pyridoxine hydrochloride
Drug: Rifampin

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 2000
Study Completion Date: September 1999
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.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000638

  Show 76 Study Locations
Sponsors and Collaborators
Hoechst Marion Roussel
Lederle Laboratories
Investigators
Study Chair: Chaisson R
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000638     History of Changes
Other Study ID Numbers: ACTG 177, CPCRA 004, TB/PPD+, 11152
Study First Received: November 2, 1999
Last Updated: March 29, 2012
Health Authority: Unspecified

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:
Acquired Immunodeficiency Syndrome
Communicable Diseases
HIV Infections
Immunologic Deficiency Syndromes
Infection
Tuberculosis
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Immune System Diseases
Lentivirus Infections
Mycobacterium Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Isoniazid
Pyrazinamide
Pyridoxine
Rifampin
Vitamin B 6
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antitubercular
Antimetabolites
Antitubercular Agents
Enzyme Inhibitors
Fatty Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on November 27, 2014