Clinical trial NCT00000638: Preventive Treatment Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculous Infection
Official title: Prophylaxis Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculous Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Tuberculosis
Keywords: Tuberculosis
Isoniazid
Mycobacterium tuberculosis
Pyrazinamide
Pyridoxine
Rifampin
AIDS-Related Opportunistic Infections
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
Antitubercular Agents
AIDS-Related Complex
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Hoechst Marion Roussel
name: Lederle Laboratories
First posted: 2001-08-31
Enrollment: 2000
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Children's Hosp of Los Angeles
state: California
city: Los Angeles
country: United States
facility: Univ of Southern California / LA County USC Med Ctr
state: California
city: Oakland
country: United States
facility: Highland Gen Hosp / San Francisco Gen Hosp
state: California
city: San Francisco
country: United States
facility: San Francisco Gen Hosp
state: California
city: San Francisco
country: United States
facility: Stanford at Kaiser / Kaiser Permanente Med Ctr
state: California
city: San Jose
country: United States
facility: Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
state: California
city: Stanford
country: United States
facility: San Mateo AIDS Program / Stanford Univ
state: California
city: Stanford
country: United States
facility: Stanford Univ Med Ctr
state: California
city: Sylmar
country: United States
facility: Olive View Med Ctr
state: California
city: Torrance
country: United States
facility: Harbor UCLA Med Ctr
state: California
city: New Haven
country: United States
facility: Yale Univ / New Haven
state: Connecticut
city: Washington
country: United States
facility: HIV Ctr - District of Columbia Gen Hosp
state: District of Columbia
city: Washington
country: United States
facility: Whitman - Walker Clinic / Georgetown Univ Med Ctr
state: District of Columbia
city: Washington
country: United States
facility: Georgetown Univ Med Ctr
state: District of Columbia
city: Washington
country: United States
facility: Howard Univ
state: District of Columbia
city: Miami
country: United States
facility: Univ of Miami School of Medicine
state: Florida
city: Honolulu
country: United States
facility: Queens Med Ctr
state: Hawaii
city: Honolulu
country: United States
facility: Univ of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Children's Mem Hosp Family Cln / Northwestern Univ Med Schl
state: Illinois
city: Chicago
country: United States
facility: Northwestern Univ Med School
state: Illinois
city: Chicago
country: United States
facility: Rush Presbyterian - Saint Luke's Med Ctr
state: Illinois
city: Chicago
country: United States
facility: Louis A Weiss Memorial Hosp
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ Hosp
state: Indiana
city: Baltimore
country: United States
facility: State of MD Div of Corrections / Johns Hopkins Univ Hosp
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hosp
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess - West Campus
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Med Ctr of Springfield
state: Massachusetts
city: Saint Louis
country: United States
facility: St Louis Regional Hosp / St Louis Regional Med Ctr
state: Missouri
city: Omaha
country: United States
facility: Univ of Nebraska Med Ctr
state: Nebraska
city: Newark
country: United States
facility: Univ of Medicine & Dentistry of New Jersey / Univ Hosp
state: New Jersey
city: Newark
country: United States
facility: Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl
state: New Jersey
city: Albany
country: United States
facility: Adirondack Med Ctr at Saranac Lake
state: New York
city: Albany
country: United States
facility: Albany Med College / Division of HIV Medicine A158
state: New York
city: Albany
country: United States
facility: Mid - Hudson Care Ctr
state: New York
city: Bronx
country: United States
facility: Bronx Municipal Hosp Ctr/Jacobi Med Ctr
state: New York
city: Bronx
country: United States
facility: Comprehensive Health Care Ctr / Bronx Municipal Hosp
state: New York
city: Bronx
country: United States
facility: Montefiore Drug Treatment Ctr / Bronx Municipal Hosp
state: New York
city: Bronx
country: United States
facility: Montefiore Family Health Ctr / Bronx Municipal Hosp
state: New York
city: Bronx
country: United States
facility: Samaritan Village Inc / Bronx Municipal Hosp
state: New York
city: Bronx
country: United States
facility: Jack Weiler Hosp / Bronx Municipal Hosp
state: New York
city: Bronx
country: United States
facility: Montefiore Med Ctr / Bronx Municipal Hosp
state: New York
city: Bronx
country: United States
facility: Montefiore Med Ctr Adolescent AIDS Program
state: New York
city: Bronx
country: United States
facility: North Central Bronx Hosp / Bronx Municipal Hosp
state: New York
city: Brooklyn
country: United States
facility: Interfaith Med Ctr
state: New York
city: Brooklyn
country: United States
facility: SUNY / Health Sciences Ctr at Brooklyn
state: New York
city: Buffalo
country: United States
facility: SUNY / Erie County Med Ctr at Buffalo
state: New York
city: East Meadow
country: United States
facility: Nassau County Med Ctr
state: New York
city: Elmhurst
country: United States
facility: City Hosp Ctr at Elmhurst / Mount Sinai Hosp
state: New York
city: Manhasset
country: United States
facility: North Shore Univ Hosp
state: New York
city: New York
country: United States
facility: Beth Israel Med Ctr
state: New York
city: New York
country: United States
facility: Bellevue Hosp / New York Univ Med Ctr
state: New York
city: New York
country: United States
facility: Saint Clare's Hosp and Health Ctr
state: New York
city: New York
country: United States
facility: Cornell Univ Med Ctr
state: New York
city: New York
country: United States
facility: Saint Luke's - Roosevelt Hosp Ctr
state: New York
city: New York
country: United States
facility: Mount Sinai Med Ctr
state: New York
city: New York
country: United States
facility: Columbia Presbyterian Med Ctr
state: New York
city: Stony Brook
country: United States
facility: SUNY - Stony Brook
state: New York
city: Syracuse
country: United States
facility: SUNY / State Univ of New York
state: New York
city: Chapel Hill
country: United States
facility: Univ of North Carolina
state: North Carolina
city: Greensboro
country: United States
facility: Moses H Cone Memorial Hosp
state: North Carolina
city: Raleigh
country: United States
facility: Wake County Dept of Health
state: North Carolina
city: Cincinnati
country: United States
facility: Univ of Cincinnati
state: Ohio
city: Cincinnati
country: United States
facility: Univ of Kentucky Lexington
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve Univ
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Med Ctr
state: Ohio
city: Columbus
country: United States
facility: Ohio State Univ Hosp Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Girard Med Ctr
state: Pennsylvania
city: Philadelphia
country: United States
facility: Univ of Pennsylvania at Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson Univ Hosp
state: Pennsylvania
city: Charleston
country: United States
facility: Med Univ of South Carolina / UNC
state: South Carolina
city: West Columbia
country: United States
facility: Julio Arroyo
state: South Carolina
city: Nashville
country: United States
facility: Meharry Med College
state: Tennessee
city: Galveston
country: United States
facility: Univ of Texas Galveston
state: Texas
city: Houston
country: United States
facility: Houston Clinical Research Network
state: Texas
city: San Juan
country: Puerto Rico
facility: Univ of Puerto Rico
Study officials:
name: Chaisson R
role: STUDY_CHAIR
References:
citation: Halsey N, et al. Twice weekly INH vs RIF and PZA for TB prophylaxis in HIV infected adults. Natl Conf Hum Retroviruses Relat Infect (2nd). 1995 Jan 29-Feb 2:55
citation: Gordin F, Chaisson RE, Matts JP, Miller C, de Lourdes Garcia M, Hafner R, Valdespino JL, Coberly J, Schechter M, Klukowicz AJ, Barry MA, O'Brien RJ. Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons: an international randomized trial. Terry Beirn Community Programs for Clinical Research on AIDS, the Adult AIDS Clinical Trials Group, the Pan American Health Organization, and the Centers for Disease Control and Prevention Study Group. JAMA. 2000 Mar 15;283(11):1445-50. doi: 10.1001/jama.283.11.1445.