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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2009 by Tuberculosis Research Centre, India.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
National AIDS Control Organisation
Indian Council of Medical Research
Information provided by:
Tuberculosis Research Centre, India
ClinicalTrials.gov Identifier:
NCT00332306
First received: May 30, 2006
Last updated: October 7, 2009
Last verified: January 2009
  Purpose

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).


Condition Intervention Phase
Tuberculosis
Human Immunodeficiency Virus Infections
Drug: Didanosine, Lamivudine, Efavirenz
Drug: Didanosine, Lamivudine, Nevirapine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To compare the response to treatment between partially supervised drug administration and unsupervised drug administration. [ Time Frame: Dec 2009 ] [ Designated as safety issue: No ]
  • To compare the tolerability and toxicity attributable to study drugs. [ Time Frame: Dec 2009 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 180
Study Start Date: June 2006
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 61 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00332306

Locations
India
Tuberculosis Research Centre
Chennai, Tamilnadu, India, 600031
Sponsors and Collaborators
Tuberculosis Research Centre, India
National AIDS Control Organisation
Indian Council of Medical Research
Investigators
Principal Investigator: Soumya Swaminathan, MD Tuberculosis Research Centre, India
Study Director: PR Narayanan, PhD Tuberculosis Research Centre, India
  More Information

Additional Information:
Publications:

Responsible Party: Dr Soumya Swaminathan, Tuberculosis Research Centre
ClinicalTrials.gov Identifier: NCT00332306     History of Changes
Other Study ID Numbers: trc23
Study First Received: May 30, 2006
Last Updated: October 7, 2009
Health Authority: India: Indian Council of Medical Research

Keywords provided by Tuberculosis Research Centre, India:
Once daily antiretroviral treatment
Concomitant antituberculosis treatment
HIV Infections

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
Antitubercular Agents
Didanosine
Nevirapine
Lamivudine
Efavirenz
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014