Short Course Intermittent Regimens for the Treatment of HIV-Associated Tuberculosis - Full Text View

Purpose

Title: Randomized clinical trial to assess the efficacy of short course intermittent regimens for the treatment of HIV-associated tuberculosis

Phase: Phase III trial

Population: 300 HIV positive patients with tuberculosis.

Number of Sites:Four

Tuberculosis Research Centre, Chennai
Government General Hospital, Chennai
Government Hospital of Thoracic Medicine, Tambaram
Government Rajaji Hospital, Madurai

Study Duration:36 months

Study Objective:To study the efficacy of the standard RNTCP Category I regimen (2EHRZ3 / 4RH3) the control arm vs. an extended continuation phase regimen 2EHRZ3 / 7 RH3 in the treatment of pulmonary and extrapulmonary TB in the HIV positive patients.

2. To study the relationship between stage of HIV disease and response to anti-TB treatment.

3. To study recurrences and their nature (relapse/re-infection) in detail by using RFLP analysis.

Study Design:It is a two armed prospective randomized open label controlled clinical trial with stratified random allocation based on CD4 count and sputum smear grade.

All enrolled patients will be treated according to the RNTCP guidelines during the intensive phase. In the continuation phase, Cat I patients will be stratified by CD4 counts and by smear grade, and randomly allocated either to the standard RNTCP regimen, or to an alternative extended regimen (2EHRZ3/4RH3 or 2EHRZ3/7RH3).

Condition	Intervention	Phase
Tuberculosis Human Immunodeficiency Virus Infections	Drug: Anti-TB drugs (Ethambutol, Isoniazid, Rifampicin and Pyrazinamide)	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Randomized Clinical Trial to Assess the Efficacy of Short Course Intermittent Regimens for the Treatment of HIV-Associated Tuberculosis

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS Tuberculosis

Drug Information available for: Isoniazid Ethambutol Pyrazinamide Ethambutol hydrochloride Rifampin

U.S. FDA Resources

Further study details as provided by Tuberculosis Research Centre, India:

Primary Outcome Measures:

Primary outcome measures are TB cure and relapse rates [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Secondary Outcome measure is mortality rates. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment:	300
Study Start Date:	February 2001
Estimated Study Completion Date:	September 2008
Estimated Primary Completion Date:	September 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 2EHRZ3/4RH3	Drug: Anti-TB drugs (Ethambutol, Isoniazid, Rifampicin and Pyrazinamide) Arm 1 is a standard six-month intermittent regimen consisting of Ethambutol, Isoniazid, Rifampicin and Pyrazinamide given thrice weekly for 2 months followed by Rifampicin and Isoniazid given thrice-weekly for 4 months.
Experimental: 2 2EHRZ3/7RH3	Drug: Anti-TB drugs (Ethambutol, Isoniazid, Rifampicin and Pyrazinamide) Arm 1 is a standard six-month intermittent regimen consisting of Ethambutol, Isoniazid, Rifampicin and Pyrazinamide given thrice weekly for 2 months followed by Rifampicin and Isoniazid given thrice-weekly for 7 months.

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Eligibility

Ages Eligible for Study:	15 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age > 15 years
HIV positivity (on 2 different ELISA tests on the same blood sample)
Living in Chennai or Madurai within a defined area of intake - 25 km radius.
Likely to remain in the same area for at least three years after start of treatment
The patient is judged to be cooperative and willing for thrice-weekly attendance for the first 2/3 months and once-weekly thereafter for the next 4 to 7 months
Is agreeable for home visits
No major complications of HIV disease like encephalopathy, renal or hepatic disease or end stage disease.
No other medical condition that might interfere with management like diabetes, convulsions, serious cardiac disease.
Patients who fulfill laboratory criteria (hemoglobin =>70 g/L, granulocyte count >1.1 X 109/L, platelet count > 100X 109/L, serum alanine amino transferase concentration <2.5 times the upper limit of normal, serum creatinine concentration <1.1mg%, random blood sugar < 140 mg/dl) will be enrolled in to the study

Exclusion Criteria:

Resides outside area of intake.
Pregnancy and lactation.
Patients with major psychiatric illnesses and severe depression
Major complications of HIV disease like encephalopathy, renal or hepatic disease or end stage disease
Serious cardiac disease (CCF, IHD), uncontrolled diabetes mellitus, convulsions, cancer, moribund state
Previous antituberculosis treatment for more than 1 month.
Patients on ART

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00376012

Locations

India
Tuberculosis Research Centre
Chennai, Tamilnadu, India, 600 031

Sponsors and Collaborators

Tuberculosis Research Centre, India

Investigators

Principal Investigator:

Soumya Swaminathan, MD MNAMS

Tuberculosis Research Centre, India

More Information

Additional Information:

Tuberculosis Research Centre This link exits the ClinicalTrials.gov site

Indian Council of Medical Research This link exits the ClinicalTrials.gov site

Publications:

Chaisson RE, Clermont HC, Holt EA, Cantave M, Johnson MP, Atkinson J, Davis H, Boulos R, Quinn TC, Halsey NA. Six-month supervised intermittent tuberculosis therapy in Haitian patients with and without HIV infection. Am J Respir Crit Care Med. 1996 Oct;154(4 Pt 1):1034-8.

El-Sadr WM, Perlman DC, Denning E, Matts JP, Cohn DL. A review of efficacy studies of 6-month short-course therapy for tuberculosis among patients infected with human immunodeficiency virus: differences in study outcomes. Clin Infect Dis. 2001 Feb 15;32(4):623-32. Epub 2001 Feb 9. Review.

Perriens JH, St Louis ME, Mukadi YB, Brown C, Prignot J, Pouthier F, Portaels F, Willame JC, Mandala JK, Kaboto M, et al. Pulmonary tuberculosis in HIV-infected patients in Zaire. A controlled trial of treatment for either 6 or 12 months. N Engl J Med. 1995 Mar 23;332(12):779-84.

Kassim S, Sassan-Morokro M, Ackah A, Abouya LY, Digbeu H, Yesso G, Coulibaly IM, Coulibaly D, Whitaker PJ, Doorly R, et al. Two-year follow-up of persons with HIV-1- and HIV-2-associated pulmonary tuberculosis treated with short-course chemotherapy in West Africa. AIDS. 1995 Oct;9(10):1185-91.

Alwood K, Keruly J, Moore-Rice K, Stanton DL, Chaulk CP, Chaisson RE. Effectiveness of supervised, intermittent therapy for tuberculosis in HIV-infected patients. AIDS. 1994 Aug;8(8):1103-8.

el-Sadr WM, Perlman DC, Matts JP, Nelson ET, Cohn DL, Salomon N, Olibrice M, Medard F, Chirgwin KD, Mildvan D, Jones BE, Telzak EE, Klein O, Heifets L, Hafner R. Evaluation of an intensive intermittent-induction regimen and duration of short-course treatment for human immunodeficiency virus-related pulmonary tuberculosis. Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) and the AIDS Clinical Trials Group (ACTG). Clin Infect Dis. 1998 May;26(5):1148-58.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Swaminathan S, Narendran G, Venkatesan P, Iliayas S, Santhanakrishnan R, Menon PA, Padmapriyadarsini C, Ramachandran R, Chinnaiyan P, Suhadev M, Sakthivel R, Narayanan PR. Efficacy of a 6-month versus 9-month intermittent treatment regimen in HIV-infected patients with tuberculosis: a randomized clinical trial. Am J Respir Crit Care Med. 2010 Apr 1;181(7):743-51. Epub 2009 Dec 3.

Responsible Party:	Soumya Swaminathan, Tuberculosis Research centre
ClinicalTrials.gov Identifier:	NCT00376012 History of Changes
Other Study ID Numbers:	trc20A
Study First Received:	September 13, 2006
Last Updated:	June 10, 2008
Health Authority:	India: Indian Council of Medical Research

Keywords provided by Tuberculosis Research Centre, India:

Chemotherapy for TB in HIV infection

Additional relevant MeSH terms:

Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Tuberculosis
Virus Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections

Bacterial Infections
Ethambutol
Isoniazid
Pyrazinamide
Rifampin
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents

ClinicalTrials.gov processed this record on March 03, 2013