A Randomized Trial of Three Regimens to Prevent Tuberculosis in HIV-Infected Patients With Anergy

This study has been completed.
Sponsor:
Information provided by:
Sociedad Andaluza de Enfermedades Infecciosas
ClinicalTrials.gov Identifier:
NCT00402610
First received: November 18, 2006
Last updated: October 23, 2008
Last verified: November 2006
  Purpose

INTRODUCTION. To evaluate the efficacy of three regimens of prophylactic therapy for tuberculosis in HIV-infected patients with anergy. METHODS. Prospective, multi-center, randomized, comparative, and open clinical trial. Anergy was defined as absence of induration in response to three antigens (PPD, Candida albicans and parotiditis antigen) applied by the Mantoux method. Patients were randomized into one of the following prophylactic treatment groups: isoniazid for six months (6H), rifampin plus isoniazid for three months (3RH), rifampin plus pyrazinamide for two months (2RZ) or no treatment (NT). After completion of treatment, patients were followed up for two years.


Condition Intervention Phase
HIV Infections
Tuberculosis
Drug: isoniazid, rifampin + isoniazid, rifampin + pyrazinamide or not treatment
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Randomized Trial of Three Regimens to Prevent Tuberculosis in HIV-Infected Patients With Anergy

Resource links provided by NLM:


Further study details as provided by Sociedad Andaluza de Enfermedades Infecciosas:

Primary Outcome Measures:
  • Development of tuberculosis

Secondary Outcome Measures:
  • Suspension of chemoprophylaxis due to adverse effects
  • Mortality

Estimated Enrollment: 332
Study Start Date: January 1994
Estimated Study Completion Date: December 1998
Detailed Description:

This study is a controlled, open, randomized, multi-center clinical trial. The study was authorized by the Clinical Research Ethics Committee of all participating centers and informed written consent was obtained from all the patients included. The cutaneous anergy was defined by the absence of a reaction (0 mm) to skin reactivity tests with tuberculin, Candida albicans, and parotiditis antigens 72 hours after inoculation. The patients were randomzed into one of the following four groups: isoniazid for 6 months (6H), rifampin plus isoniazid for 3 months (3RH), rifampin plus pyrazinamide for 2 months (2RZ) or no treatment (NT). All of the participating subjects underwent a basal study that included clinical and epidemiological history, chest x-ray, hemogram, analysis of serum creatinine concentrations, uric acid, AST, ALT, alkaline phosphatase, and total bilirubin, as well as a CD4+ T-lymphocyte count.During prophylactic treatment, patients were evaluated every 15 days for the first two months and monthly thereafter. At each check-up it was determined whether or not the patient was following the treatment properly and whether there were any adverse effects. Therapeutic completion was defined as taking at least 80% of the total prescribed dosages.Chemoprophylaxis was discontinued whenever a patient requested to do so or for any of the following reasons: appearance of Grade 3 or 4 side effects that could be attributed to the drugs used in the study; increases in AST and/or ALT values of three times or more their basal values; development of TB; or diagnosis of any disease that made interruption of the treatment advisable.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV infection confirmed by ELISA and Western blot
  • Age between 18 and 65 years
  • Life expectancy greater than two years
  • Cutaneous anergy defined by the absence of a reaction (0 mm) to skin reactivity tests with tuberculin, Candida albicans, and parotiditis antigens 72 hours after inoculation.

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.
  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: NCT00402610

Locations
Spain
Hospital Universitario Reina Sofía
Córdoba, Spain, 14002
Sponsors and Collaborators
Sociedad Andaluza de Enfermedades Infecciosas
Investigators
Study Chair: Antonio Rivero, MD PhD Hospital Universitario Reina Sofía, Córdoba, Spain
Principal Investigator: Luis Lopez-Crtés, MD, PhD Hospital Universitario Virgen del Rocío, Sevilla, Spain
Principal Investigator: Rafael Castillo, MD 3 Sección de Enfermedades Infecciosas. Hospital Clínico Universitario San Cecilio. Avda. Dr. Oloriz 16. 18012 Granada
Principal Investigator: José Verdejo, MD Servicio de Enfermedades Infecciosas. Hospital Carlos III. Sinesio Delgado 10. 28029 Madrid
Principal Investigator: Miguel Angel García, MD Sección de Enfermedades Infecciosas. Hospital Carlos Haya. Avda. Carlos Haya s/n. 29010 Málaga.
Principal Investigator: Felipes Diez, MD Servicio de Medicina Interna. Hospital Torrecárdenas. Paraje de Torrecárdenas s/n. 04009 Almería.
Principal Investigator: Jose Carlos Escribano, MD Sección de Enfermedades Infecciosas. Hospital Universitario Puerta del Mar. Avda. Ana de Viya, 21. 11009 Cádiz. Spain
Principal Investigator: Jesús Canueto, MD Sección de Enfermedades Infecciosas. Hospital Punta Europa de Algeciras. Ctra de Getares s/n. 11207 Algeciras (Cádiz)., Spain
Principal Investigator: Manuel Marquez, MD Unidad de Enfermedades Infecciosas. Hospital Universitario Virgen de la Victoria, Campus Universitario Teatinos s/n. 29010 Málaga.
Principal Investigator: Juan Jose Hernandez, MD Unidad de Enfermedades Infecciosas. Hospital Ciudad de Jaén, Avda del Ejército Español, 10. 23007 Jaén, Spain.
Principal Investigator: Juan Pasquau, MD Sección de Enfermedades Infecciosas. Hospital Universitario Virgen de las Nieves. Avda de las Fuerzas Armadas, 2. 18014 Granada, Spain.
Principal Investigator: Fernando Lozano, MD PhD Sección de Enfermedades Infecciosas. Hospital Universitario Virgen de Valme. Ctra. de Cádiz s/n. 41012 Sevilla, Spain
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00402610     History of Changes
Other Study ID Numbers: GAEI 94/0071a, FIS 94/0071A
Study First Received: November 18, 2006
Last Updated: October 23, 2008
Health Authority: Spain: Ministry of Health

Keywords provided by Sociedad Andaluza de Enfermedades Infecciosas:
HIV
Tuberculosis
Chemoprophylaxis
Anergy
AIDS

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Tuberculosis
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Mycobacterium Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Isoniazid
Pyrazinamide
Rifampin
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antitubercular
Antimetabolites
Antitubercular Agents
Enzyme Inhibitors
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Leprostatic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 23, 2014