Safety and Efficacy of Two Once Daily Anti Retroviral Treatment Regimens Along With Anti-tuberculosis Treatment

October 7, 2009 updated by: Tuberculosis Research Centre, India

Evaluation of Safety and Efficacy of Two Different Once Daily Anti Retroviral Treatment Regimens Along With Anti-tuberculosis Treatment in Patients With HIV-1 and Tuberculosis

Protocol Summary

Title: Evaluation of safety and efficacy of two different once daily anti-retroviral treatment regimens along with anti-tuberculosis treatment in patients with HIV-1 and tuberculosis - Randomized Controlled Clinical Trial

Phase: Phase III trial

Population: 180 HIV-1 positive patients with tuberculosis

Number of Sites: Four.

  1. Tuberculosis Research Centre, Chennai
  2. Government Medical College, Vellore
  3. Government Hospital of Thoracic Medicine, Tambaram
  4. Government Rajaji Hospital, Madurai

Study Duration: 26 months including 24 months of ART.

Study Objectives:

Primary Objective To compare the efficacy and safety of two different once-daily anti-retroviral treatment regimens (along with standard anti-tuberculosis treatment) in patients with HIV-1 and tuberculosis, by using virologic end points.

Secondary Objective To compare the efficacy of antiretroviral treatment given under partial supervision with unsupervised treatment (once a month supply).

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Description of Agent or Intervention:

The study intervention is to start patients with HIV and tuberculosis on anti-retroviral treatment along with the continuation phase of anti-tuberculosis treatment (ATT)ie after completion of first two months of treatment. The anti-TB regimen used in this trial will be 2EHRZ3/4RH3. Two different once-daily regimens are being compared for their efficacy and adverse event profile, namely ddI + 3TC + NVP versus ddI + 3TC + EFZ. The primary aim is to study the outcome of patients treated with both ART and ATT at 6 months (24 weeks of ART). A secondary objective is to compare the utility of partially supervised directly observed treatment with unsupervised administration of anti-retroviral drugs.

Patients with HIV-1 infection and active tuberculosis (pulmonary and extrapulmonary) will be started on a four-drug intermittent short-course anti-TB regimen on recruitment to the trial. They will be randomized at the end of intensive phase of ATT to receive either of the ART regimens and the outcome measured at the end of 6 months. During this phase, both ATT and ART will be given under supervision three times a week. Patients with viral load < 400 copies/ml(favourable outcome) at this time point will be randomized to receive ART either by partial observation of treatment (three times a week)or monthly supply (unsupervised administration) and final outcome will be measured at the end of 24 months of ART. The study will provide information on the comparative efficacy of the two regimens when given with anti-TB treatment as well as any added advantage that direct observation of treatment may provide.

Study Type

Interventional

Enrollment (Anticipated)

180

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
    • Tamilnadu
      • Chennai, Tamilnadu, India, 600031
        • Tuberculosis Research Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 61 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age > 18 years

  2. a) Newly diagnosed sputum smear positive tuberculosis (at least 1 out of 6 sputum specimen should be positive by smear) b)Miliary tuberculosis, mediastinal/hilar lymphadenopathy, diagnosed by chest radiography or CT scan (irrespective of sputum smear status).

    c)TB lymphadenitis with histopathological/bacteriological evidence of TB d)Pleural effusion with biochemical/cytological/bacteriological evidence of TB

  3. HIV-1 positivity (on 2 different rapid tests on the same blood sample)
  4. CD4 cell counts less than 250 cells/mm3
  5. Likely to remain in the same area for at least two years after start of treatment.
  6. Willingness to stay in the hospital for 2 weeks during initiation of ART, and attend the clinic thrice weekly for the entire period of the study (up to 2 years).
  7. Willingness for home visits, and to attend for investigations, supervised treatment and follow-up as required.
  8. Within the area of intake (25 kms from any of the TRC subcentres).
  9. Willingness to use contraception during trial period.

Exclusion Criteria:

  1. Resides outside area of intake.
  2. Pregnancy and lactation.
  3. Patients with major psychiatric illnesses and severe depression
  4. Major complications of HIV disease like encephalopathy, renal (Serum creatinine level > 1.2 mgs/dl) or hepatic disease (Serum bilirubin > 2.0 times upper limit of normal, Serum transaminases > 2.5 times upper limit of normal), serum amylase > 2 times upper limit of normal with serum lipase > 1.5 times upper limit of normal.
  5. Serious cardiac disease (CCF, IHD), uncontrolled diabetes mellitus, cancer, moribund state
  6. Previous antituberculosis treatment for more than 1 month.
  7. Previous antiretroviral treatment for more than 1 month
  8. Patients with CD4 cell count >250 cells/mm3.
  9. HIV-2 infection alone or in combination with HIV-1.
  10. Patients currently using alcohol, IV drugs & other substance abuse.
  11. Unwilling to use contraception & avoid pregnancy.
  12. Unwilling to HIV/TB screening and participation in trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 2
Didanosine + Lamivudine + Nevirapine
Drug: Didanosine, Lamivudine, Nevirapine
Didanosine 250 mg once daily for patients < 60kg, 400 mg OD patients > 60kg Lamivudine 300 mg once daily Nevirapine 400 mg once daily All drugs will be given for 24 months
Active Comparator: 1
Didanosine + Lamivudine + Efavirenz
Drug: Didanosine, Lamivudine, Efavirenz
Didanosine 250mg patients <60kg, 400mg patients > 60kg once daily Lamivudine 300 mg once daily Efavirenz 600 mg once daily All drugs will be given for 24 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Suppression of Viral load to < 400 copies/ml or a two log reduction in viral load from the baseline value at the end of 6 months and a viral load <400 copies/ml at 24 months of antiretroviral therapy
Time Frame: Dec 2008
Dec 2008

Secondary Outcome Measures

Outcome Measure
Time Frame
To compare the response to treatment between partially supervised drug administration and unsupervised drug administration.
Time Frame: Dec 2009
Dec 2009
To compare the tolerability and toxicity attributable to study drugs.
Time Frame: Dec 2009
Dec 2009

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tuberculosis Research Centre, India

Collaborators

Indian Council of Medical Research
National AIDS Control Organisation

Investigators

  • Principal Investigator: Soumya Swaminathan, MD, Tuberculosis Research Centre, India
  • Study Director: PR Narayanan, PhD, Tuberculosis Research Centre, India

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2006

Primary Completion (Anticipated)

June 1, 2009

Study Completion (Anticipated)

December 1, 2011

Study Registration Dates

First Submitted

May 30, 2006

First Submitted That Met QC Criteria

May 30, 2006

First Posted (Estimate)

June 1, 2006

Study Record Updates

Last Update Posted (Estimate)

October 8, 2009

Last Update Submitted That Met QC Criteria

October 7, 2009

Last Verified

January 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • trc23

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Tuberculosis

Clinical Trials on Didanosine, Lamivudine, Nevirapine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Switzerland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe