Preventive Therapy for Tuberculosis in HIV Infected Persons - Full Text View

Sponsors and Collaborators:	Tuberculosis Research Centre, India United States Agency for International Development (USAID)
Information provided by:	Tuberculosis Research Centre, India
ClinicalTrials.gov Identifier:	NCT00351702

Purpose

Title: Evaluation of efficacy of two different preventive therapy regimens for tuberculosis in HIV infected persons

Phase: Phase III trial

Population: 650 HIV positive patients without tuberculosis

Number of sites: Three

Tuberculosis Research centre, Chennai
Government General Hospital, Chennai
Government Rajaji Hospital, Madurai

Study Duration: 36 months

Study Objectives: To compare the efficacy of two TB preventive therapy regimens in reducing the incidence of tuberculosis and mortality among HIV-infected persons

Study Design:

The study will be a two-armed prospective randomized clinical trial among HIV- positive patients without active tuberculosis. Enrolled patients will be assigned to one of the two unsupervised self-administered treatment regimens i.e. EH for 6 months or INH alone for 3 years. At the end of a 3-year follow-up, incidence of TB and overall mortality will be compared in each group.

Study Endpoints:The primary end point of the study will be development of tuberculosis and the secondary endpoints will include adverse drug reactions and mortality rate.

Condition	Intervention	Phase
Human Immunodeficiency Virus Tuberculosis	Drug: Isoniazid and Ethambutol	Phase III

MedlinePlus related topics: AIDS Tuberculosis

Drug Information available for: Ethambutol hydrochloride Ethambutol Isoniazid Ftivazide

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	Evaluation of Two Different Preventive Therapy Regimens for Tuberculosis in HIV Infected Persons

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

Primary Outcome Measures:

Primary outcome measure is the development of tuberculosis.

Secondary Outcome Measures:

Secondary outcome measures include adverse drug reactions and mortality rate.

Estimated Enrollment:	650
Study Start Date:	February 2001
Estimated Study Completion Date:	September 2008

Detailed Description:

Study population and enrollment:

All HIV positive patients seeking care at one of the study centers, above the age of 15 years, not suffering from a serious illness, non-pregnant, and in whom TB was ruled out using the enhanced screening process, will be enrolled in the study. The consent form for prophylaxis trial will be read to the patients in the local language and written consent will be obtained from willing patients

Randomization and Dosing:

All patients enrolled in the prevention trial will be randomized to one of the study groups using a permuted block randomization scheme of four. Stratification will be done by Mantoux reading (>5mm and ≤5mm). The group assignment list will be generated centrally before the start of trial and sequentially numbered sealed envelopes containing the study group assigned will be prepared independently. At the initiation of prophylaxis, each patient will be counseled about the importance of taking drugs regularly. Patients will be asked to return the empty packets as well as unused tablets at each monthly visit.

The treatment regimens in each study group will be as follows:

Ethambutol (800 mg) and Isoniazid (300 mg) daily for six months, self-administered, collected once in fifteen days.
Isoniazid (300 mg) daily for 3 years with fortnightly collection of drugs Subjects in both study groups will receive 10 mg of Pyridoxine daily during treatment.

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 fortnightly attendance for the next 3 years
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 > 7.0g/l,granulocyte count>11,000/l, platelet count > 1 lakh/l. serum alanine amino transferase concentration < 2.5 times the upper limit of normal and serum creatinine concentration < 1.1 mgs%, random blood sugar < 140 mgs%) will be enrolled into 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: NCT00351702

Locations

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

Sponsors and Collaborators

Tuberculosis Research Centre, India

United States Agency for International Development (USAID)

Investigators

Principal Investigator:

Soumya Swaminathan, MD MNAMS

Tuberculosis Research Centre, India

More Information

Tuberculosis Research Centre This link exits the ClinicalTrials.gov site

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

Publications:

Bucher HC, Griffith LE, Guyatt GH, Sudre P, Naef M, Sendi P, Battegay M. Isoniazid prophylaxis for tuberculosis in HIV infection: a meta-analysis of randomized controlled trials. AIDS. 1999 Mar 11;13(4):501-7.

Wilkinson D, Squire SB, Garner P. Effect of preventive treatment for tuberculosis in adults infected with HIV: systematic review of randomised placebo controlled trials. BMJ. 1998 Sep 5;317(7159):625-9.

Hawken MP, Meme HK, Elliott LC, Chakaya JM, Morris JS, Githui WA, Juma ES, Odhiambo JA, Thiong'o LN, Kimari JN, Ngugi EN, Bwayo JJ, Gilks CF, Plummer FA, Porter JD, Nunn PP, McAdam KP. Isoniazid preventive therapy for tuberculosis in HIV-1-infected adults: results of a randomized controlled trial. AIDS. 1997 Jun;11(7):875-82.

Whalen CC, Johnson JL, Okwera A, Hom DL, Huebner R, Mugyenyi P, Mugerwa RD, Ellner JJ. A trial of three regimens to prevent tuberculosis in Ugandan adults infected with the human immunodeficiency virus. Uganda-Case Western Reserve University Research Collaboration. N Engl J Med. 1997 Sep 18;337(12):801-8.

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.

Study ID Numbers:	trc20B
Study First Received:	July 12, 2006
Last Updated:	April 7, 2008
ClinicalTrials.gov Identifier:	NCT00351702
Health Authority:	India: Indian Council of Medical Research

Keywords provided by Tuberculosis Research Centre, India:

Preventive therapy

Study placed in the following topic categories:

Bacterial Infections
Sexually Transmitted Diseases, Viral
Acquired Immunodeficiency Syndrome
Immunologic Deficiency Syndromes
Virus Diseases
Gram-Positive Bacterial Infections
HIV Infections

Sexually Transmitted Diseases
Mycobacterium Infections
Tuberculosis
Ethambutol
Retroviridae Infections
Isoniazid

Additional relevant MeSH terms:

Anti-Infective Agents
Anti-Bacterial Agents
RNA Virus Infections
Slow Virus Diseases
Immune System Diseases

Therapeutic Uses
Lentivirus Infections
Antitubercular Agents
Pharmacologic Actions
Actinomycetales Infections

ClinicalTrials.gov processed this record on January 14, 2009