- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00351702
Preventive Therapy for Tuberculosis in HIV Infected Persons
Evaluation of Two Different Preventive Therapy Regimens for Tuberculosis in HIV Infected Persons
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Tamilnadu
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Chennai, Tamilnadu, India, 600 031
- Tuberculosis Research Centre
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 -
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Isoniazid
Isoniazid (300mg) daily for 36 months
|
Isoniazid (300mg) with Ethambutol (800mg) daily for 6 months
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Primary outcome measure is the development of tuberculosis.
Time Frame: September 2008
|
September 2008
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Secondary outcome measures include adverse drug reactions and mortality rate.
Time Frame: September 2008
|
September 2008
|
Collaborators and Investigators
Investigators
- Principal Investigator: Soumya Swaminathan, MD MNAMS, Tuberculosis Research Centre, India
Publications and helpful links
General Publications
- 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. doi: 10.1001/jama.283.11.1445.
- 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. doi: 10.1056/NEJM199709183371201.
- 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. doi: 10.1097/00002030-199903110-00009.
- 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. doi: 10.1136/bmj.317.7159.625.
- 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. doi: 10.1097/00002030-199707000-00006.
- Swaminathan S, Menon PA, Gopalan N, Perumal V, Santhanakrishnan RK, Ramachandran R, Chinnaiyan P, Iliayas S, Chandrasekaran P, Navaneethapandian PD, Elangovan T, Pho MT, Wares F, Paranji Ramaiyengar N. Efficacy of a six-month versus a 36-month regimen for prevention of tuberculosis in HIV-infected persons in India: a randomized clinical trial. PLoS One. 2012;7(12):e47400. doi: 10.1371/journal.pone.0047400. Epub 2012 Dec 14.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Bacterial Infections
- Bacterial Infections and Mycoses
- Gram-Positive Bacterial Infections
- Actinomycetales Infections
- Mycobacterium Infections
- Slow Virus Diseases
- HIV Infections
- Tuberculosis
- Acquired Immunodeficiency Syndrome
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antimetabolites
- Hypolipidemic Agents
- Lipid Regulating Agents
- Anti-Bacterial Agents
- Antitubercular Agents
- Fatty Acid Synthesis Inhibitors
- Isoniazid
- Ethambutol
Other Study ID Numbers
- trc20B
Plan for Individual participant data (IPD)
Study Data/Documents
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published manuscript
Information comments: the study has been published and has been provided in the citation. the paper conatins the required information regarding study results and conclusion
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