Clinical trial NCT00402454: Evaluation of Three Regimens of Chemoprophylaxis for Tuberculosis in Patients co-Infected by HIV and Mycobacterium Tuberculosis
Official title: Evaluation of Three Regimens of Chemoprophylaxis for Tuberculosis in Patients co-Infected by HIV and Mycobacterium Tuberculosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Keywords: HIV
Tuberculosis
Prophylaxis
AIDS
Lead sponsor: Sociedad Andaluza de Enfermedades Infecciosas
Sponsor class: NETWORK
First posted: 2006-11-22
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: To evaluate adherence and safety of three regimens of chemoprophylaxis for tuberculosis (TB) in HIV-infected patients with positive tuberculin skin test.

Detailed description: DESINGS: We performed a randomised, comparative and open clinical assay carried out in 316 HIV-infected patients. The patients were randomly assigned to one of three regimens, 108 to isoniazid for six months (6H), 103 to rifampin and isoniazid for three months (3RH), and 105 to pyrazinamide and rifampin for two months (2RZ).

RESULTS: The TB rates (cases per 100 persons/year) in the three treatment groups were 3.4 in 6H, 4.5 in 3RH and 1.9 in 2RZ. The relative risk for TB with 6H as compared with 2RZ was 1.76, and with 3RH, 2.34. Twenty-seven percent of the patients voluntarily abandoned chemoprophylaxis and 9.7% were withdrawn due to adverse side-effects. Seven patients were withdraw due to hepatotoxicity (5 in 6H, 2 in 3RH and 0 in 2RZ). No appreciable differences were found among the three regimens.

CONCLUSION: In our study the 2RZ regimen was as safe as the 6H and 3RH regimens. We have nor observed a higher incidence of hepatotoxicity in patients who received 2RZ.

Eligibility criteria: Inclusion Criteria:

* HIV infection confirmed by ELISA and Western blot
* Age between 18 and 65 years
* Life expectancy greater than two years
* Reactivity to PPD \> 5 mm

Exclusion Criteria:

* Presence of active tuberculosis
* Background of previous antituberculosis therapy or chemoprophylaxis
* Presence of symptoms or signs suggesting pulmonary or extra-pulmonary tuberculosis
* History of hypersensitivity to the drugs used in the study (isoniazid, rifampin or pyrazinamide)
* Aspartate-aminotransferase and/or alanine-aminotransferase plasma concentrations more than or equal to four times their normal values, total bilirubin more than 2 mg/ml, and/or creatinine more than 2 mg/ml
* Pregnancy
* Undergoing treatment incompatible with any of the drugs used in the study.

Primary outcomes:
measure: Development of Tuberculosis
measure: Suspension of chemoprophylaxis due to adverse effects
Secondary outcomes:
measure: Suspension of chemoprophylaxis due tovoluntary withdrawal
measure: Mortality.
Other outcomes:
Locations:
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
Study officials:
affiliation: Hospital Universitario Reina Sofía, Córdoba, Spain
name: Antonio Rivero, MD PhD
role: STUDY_CHAIR
affiliation: Hospital Universitario Virgen del Rocío, Sevilla, Spain
name: Luis Lopez-Crtés, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: 3 Sección de Enfermedades Infecciosas. Hospital Clínico Universitario San Cecilio. Avda. Dr. Oloriz 16. 18012 Granada
name: Rafael Castillo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Servicio de Enfermedades Infecciosas. Hospital Carlos III. Sinesio Delgado 10. 28029 Madrid
name: José Verdejo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sección de Enfermedades Infecciosas. Hospital Carlos Haya. Avda. Carlos Haya s/n. 29010 Málaga.
name: Miguel Angel García, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Servicio de Medicina Interna. Hospital Torrecárdenas. Paraje de Torrecárdenas s/n. 04009 Almería.
name: Felipes Diez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sección de Enfermedades Infecciosas. Hospital Universitario Puerta del Mar. Avda. Ana de Viya, 21. 11009 Cádiz. Spain
name: Jose Carlos Escribano, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sección de Enfermedades Infecciosas. Hospital Punta Europa de Algeciras. Ctra de Getares s/n. 11207 Algeciras (Cádiz)., Spain
name: Jesús Canueto, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Unidad de Enfermedades Infecciosas. Hospital Universitario Virgen de la Victoria, Campus Universitario Teatinos s/n. 29010 Málaga.
name: Manuel Marquez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Unidad de Enfermedades Infecciosas. Hospital Ciudad de Jaén, Avda del Ejército Español, 10. 23007 Jaén, Spain.
name: Juan Jose Hernandez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sección de Enfermedades Infecciosas. Hospital Universitario Virgen de las Nieves. Avda de las Fuerzas Armadas, 2. 18014 Granada, Spain.
name: Juan Pasquau, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sección de Enfermedades Infecciosas. Hospital Universitario Virgen de Valme. Ctra. de Cádiz s/n. 41012 Sevilla, Spain
name: Fernando Lozano, MD PhD
role: PRINCIPAL_INVESTIGATOR
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