Preventive Therapy for Tuberculosis in HIV Infected Persons

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
Evaluation of Two Different Preventive Therapy Regimens for Tuberculosis in HIV Infected Persons

Conditions
-----------------
Human Immunodeficiency Virus, Tuberculosis

Intervention / Treatment
-----------------
* Drug: Isoniazid with Ethambutol


Participation Criteria
=================
Eligibility 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 -

Ages Eligible for Study
-----------------
Minimum Age: 15 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Isoniazid<br>Isoniazid (300mg) daily for 36 months | Drug: Isoniazid with Ethambutol<br>* Isoniazid (300mg) with Ethambutol (800mg) daily for 6 months<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary outcome measure is the development of tuberculosis. |  | September 2008 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary outcome measures include adverse drug reactions and mortality rate. |  | September 2008 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Preventive therapy