Clinical trial NCT00000959: Prophylaxis Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Suspected Latent Tuberculous Infection
Official title: Prophylaxis Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Suspected Latent Tuberculous Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Tuberculosis
Keywords: Tuberculosis
Isoniazid
Pyridoxine
AIDS-Related Opportunistic Infections
Drug Evaluation
Acquired Immunodeficiency Syndrome
Antitubercular Agents
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 600
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Med Ctr
state: California
city: San Francisco
country: United States
facility: Community Consortium of San Francisco
state: California
city: Denver
country: United States
facility: Denver CPCRA / Denver Public Hlth
state: Colorado
city: New Haven
country: United States
facility: Hill Health Corp
state: Connecticut
city: Wilmington
country: United States
facility: Wilmington Hosp / Med Ctr of Delaware
state: Delaware
city: Washington
country: United States
facility: Veterans Administration Med Ctr / Regional AIDS Program
state: District of Columbia
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: New Orleans
country: United States
facility: Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
state: Louisiana
city: Detroit
country: United States
facility: Comprehensive AIDS Alliance of Detroit
state: Michigan
city: Newark
country: United States
facility: North Jersey Community Research Initiative
state: New Jersey
city: Bronx
country: United States
facility: Bronx Lebanon Hosp Ctr
state: New York
city: Brooklyn
country: United States
facility: Addiction Research and Treatment Corp
state: New York
city: New York
country: United States
facility: Clinical Directors Network of Region II
state: New York
city: New York
country: United States
facility: Harlem AIDS Treatment Group / Harlem Hosp Ctr
state: New York
Study officials:
name: Gordin F
role: STUDY_CHAIR
References:
citation: Gordin FM, Matts JP, Miller C, Brown LS, Hafner R, John SL, Klein M, Vaughn A, Besch CL, Perez G, Szabo S, El-Sadr W. A controlled trial of isoniazid in persons with anergy and human immunodeficiency virus infection who are at high risk for tuberculosis. Terry Beirn Community Programs for Clinical Research on AIDS. N Engl J Med. 1997 Jul 31;337(5):315-20. doi: 10.1056/NEJM199707313370505.