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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000959
First received: November 2, 1999
Last updated: September 28, 2013
Last verified: September 2013
  Purpose

To evaluate the safety and effectiveness of a 6-month course of isoniazid ( INH ) in the prevention of clinical tuberculosis in anergic (having diminished or absent reactions to specific antigens) HIV-infected persons who are at high risk for tuberculous infection.

A substantial number of HIV-infected persons are anergic, and thus do not respond to the only currently available diagnostic tool for tuberculosis infection (that is, the PPD (purified protein derivative) skin test). Many of these anergic persons are, however, infected with Mycobacterium tuberculosis and eventually develop reactivation tuberculosis, causing both individual illness and spread of infection to others in the community. This study examines the possibility of using INH prophylaxis (that is, for prevention) in anergic HIV-infected patients at high risk for tuberculosis as a means of decreasing the sharp rise in the incidence of tuberculosis due to HIV infection. INH is inexpensive and relatively safe, and thus may demonstrate an acceptable risk/benefit ratio as a medication that can be given over a limited period of time to a population suspected of having, but not proved to have, M. tuberculosis infection. If this study shows INH to be safe and effective in this setting, it could have a major effect on public health in this country.


Condition Intervention
HIV Infections
Tuberculosis
Drug: Isoniazid
Drug: Pyridoxine hydrochloride

Study Type: Interventional
Study Design: Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: Prophylaxis Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Suspected Latent Tuberculous Infection

Resource links provided by NLM:


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

Estimated Enrollment: 600
Study Completion Date: June 1996
Detailed Description:

A substantial number of HIV-infected persons are anergic, and thus do not respond to the only currently available diagnostic tool for tuberculosis infection (that is, the PPD (purified protein derivative) skin test). Many of these anergic persons are, however, infected with Mycobacterium tuberculosis and eventually develop reactivation tuberculosis, causing both individual illness and spread of infection to others in the community. This study examines the possibility of using INH prophylaxis (that is, for prevention) in anergic HIV-infected patients at high risk for tuberculosis as a means of decreasing the sharp rise in the incidence of tuberculosis due to HIV infection. INH is inexpensive and relatively safe, and thus may demonstrate an acceptable risk/benefit ratio as a medication that can be given over a limited period of time to a population suspected of having, but not proved to have, M. tuberculosis infection. If this study shows INH to be safe and effective in this setting, it could have a major effect on public health in this country.

Patients are placed by a random selection process in either the INH or placebo group. One group receives INH plus pyridoxine hydrochloride ( vitamin B6 ) daily for six months. Patients in the other group receive placebo plus vitamin B6 daily for six months.

  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 therapy.
  • Pneumocystis carinii pneumonia prophylaxis.
  • Treatment for acute opportunistic infections/malignancies.

Patients must have:

  • Reasonably good health.
  • Life expectancy of at least six months.
  • Willing and able, in the clinician's opinion, to comply with the treatment and clinical management issues as outlined in the protocol.
  • HIV infection.
  • Signed informed consent.

Allowed:

  • Participation in other clinical trials as long as there is no potential activity of other study drugs against M. tuberculosis, additive toxicities between study agents, or known possible drug interactions between study drugs.
  • Must be in a high-risk group for Mycobacterium tuberculosis infection, including:
  • foreign-born from countries with a high prevalence of M. tuberculosis infection; from medically underserved low-income populations (high-risk racial or ethnic minority populations such as African Americans, Hispanic / Latinos, Native Americans, and/or the homeless, unemployed, inner city residents); alcohol or injectable drug users; or residents or former residents of high-risk, long-term care or residential facilities (correctional or mental institutions, nursing homes).

Prior Medication:

Allowed:

  • Previous 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 clinical tuberculosis, confirmed or suspected, or household contact with someone with active clinical tuberculosis.
  • History of sensitivity/intolerance to the study medication.
  • Evidence of peripheral neuropathy, i.e., signs or symptoms of paresis, paresthesias, neuromotor abnormalities, or neurosensory deficits of grade 3 or worse.
  • Evidence of acute hepatitis.

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 antituberculosis activity should be avoided, including the following:

  • Aminosalicylic acid salts, capreomycin, clofazimine, cycloserine, ethambutol, ethionamide, isoniazid, kanamycin, pyrazinamide, rifabutin, rifampin, streptomycin, or thiacetazone.

Prior Medication:

Excluded:

  • Treatment for more than 1 month (continuous or cumulative) with drugs that have known or potential antituberculous activity, other than quinolones, fluoroquinolones, and some aminoglycosides.

Patients may not have:

  • Current active clinical tuberculosis, confirmed or suspected, or household contact with someone with known active clinical tuberculosis.
  • Evidence of peripheral neuropathy, i.e., signs or symptoms of paresis, paresthesias, neuromotor abnormalities, or neurosensory deficits of grade 3 or worse.
  • Unable or unwilling to have current therapy and/or concomitant medications changed to avoid serious interaction with study medication.
  • Documented history of a positive PPD skin test.
  • Participation in other clinical trials in which there is potential activity of other study drugs against M. tuberculosis, additive toxicities between study agents, or known possible drug interactions between study drugs.

Alcohol or injectable drug users.

  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: NCT00000959

Locations
United States, California
UCLA Med Ctr
Los Angeles, California, United States, 90095
Community Consortium of San Francisco
San Francisco, California, United States, 94110
United States, Colorado
Denver CPCRA / Denver Public Hlth
Denver, Colorado, United States, 80204
United States, Connecticut
Hill Health Corp
New Haven, Connecticut, United States, 06519
United States, Delaware
Wilmington Hosp / Med Ctr of Delaware
Wilmington, Delaware, United States, 19899
United States, District of Columbia
Veterans Administration Med Ctr / Regional AIDS Program
Washington, District of Columbia, United States, 20422
United States, Georgia
AIDS Research Consortium of Atlanta
Atlanta, Georgia, United States, 30308
United States, Louisiana
Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
New Orleans, Louisiana, United States, 70112
United States, Michigan
Comprehensive AIDS Alliance of Detroit
Detroit, Michigan, United States, 48201
United States, New Jersey
North Jersey Community Research Initiative
Newark, New Jersey, United States, 07103
United States, New York
Bronx Lebanon Hosp Ctr
Bronx, New York, United States, 10456
Addiction Research and Treatment Corp
Brooklyn, New York, United States, 11201
Clinical Directors Network of Region II
New York, New York, United States, 10011
Harlem AIDS Treatment Group / Harlem Hosp Ctr
New York, New York, United States, 10037
Sponsors and Collaborators
Investigators
Study Chair: Gordin F
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000959     History of Changes
Other Study ID Numbers: CPCRA 005, 11557
Study First Received: November 2, 1999
Last Updated: September 28, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Tuberculosis
Isoniazid
Pyridoxine
AIDS-Related Opportunistic Infections
Drug Evaluation
Acquired Immunodeficiency Syndrome
Antitubercular Agents

Additional relevant MeSH terms:
Infection
Communicable Diseases
HIV Infections
Acquired Immunodeficiency Syndrome
Immunologic Deficiency Syndromes
Tuberculosis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immune System Diseases
Slow Virus Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Isoniazid
Pyridoxine
Vitamin B 6
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014