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

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Primary Purpose

Status

Unknown status

Phase

Phase 3

Locations

India

Study Type

Interventional

Intervention

Didanosine, Lamivudine, Efavirenz

Didanosine, Lamivudine, Nevirapine

About this trial

This is an interventional treatment trial for Tuberculosis focused on measuring Once daily antiretroviral treatment, Concomitant antituberculosis treatment, HIV Infections

Eligibility Criteria

18 Years - 61 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age > 18 years 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 HIV-1 positivity (on 2 different rapid tests on the same blood sample) CD4 cell counts less than 250 cells/mm3 Likely to remain in the same area for at least two years after start of treatment. 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). Willingness for home visits, and to attend for investigations, supervised treatment and follow-up as required. Within the area of intake (25 kms from any of the TRC subcentres). Willingness to use contraception during trial period. 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 (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. Serious cardiac disease (CCF, IHD), uncontrolled diabetes mellitus, cancer, moribund state Previous antituberculosis treatment for more than 1 month. Previous antiretroviral treatment for more than 1 month Patients with CD4 cell count >250 cells/mm3. HIV-2 infection alone or in combination with HIV-1. Patients currently using alcohol, IV drugs & other substance abuse. Unwilling to use contraception & avoid pregnancy. Unwilling to HIV/TB screening and participation in trial.

Sites / Locations

Tuberculosis Research Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

2

1

Arm Description

Didanosine + Lamivudine + Nevirapine

Didanosine + Lamivudine + Efavirenz

Outcomes

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

Secondary Outcome Measures

To compare the response to treatment between partially supervised drug administration and unsupervised drug administration.

To compare the tolerability and toxicity attributable to study drugs.

Full Information

NCT ID

NCT00332306

First Posted

May 30, 2006

Last Updated

October 7, 2009

Sponsor

Tuberculosis Research Centre, India

Collaborators

National AIDS Control Organisation, Indian Council of Medical Research

1. Study Identification

Unique Protocol Identification Number

NCT00332306

Brief Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2009

Overall Recruitment Status

Unknown status

Study Start Date

June 2006 (undefined)

Primary Completion Date

June 2009 (Anticipated)

Study Completion Date

December 2011 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor

Tuberculosis Research Centre, India

Collaborators

National AIDS Control Organisation, Indian Council of Medical Research

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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. Tuberculosis Research Centre, Chennai Government Medical College, Vellore Government Hospital of Thoracic Medicine, Tambaram 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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tuberculosis, Human Immunodeficiency Virus Infections

Keywords

Once daily antiretroviral treatment, Concomitant antituberculosis treatment, HIV Infections

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

2

Arm Type

Experimental

Arm Description

Didanosine + Lamivudine + Nevirapine

Arm Title

1

Arm Type

Active Comparator

Arm Description

Didanosine + Lamivudine + Efavirenz

Intervention Type

Drug

Intervention Name(s)

Didanosine, Lamivudine, Efavirenz

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Didanosine, Lamivudine, Nevirapine

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

To compare the response to treatment between partially supervised drug administration and unsupervised drug administration.

Time Frame

Dec 2009

Title

To compare the tolerability and toxicity attributable to study drugs.

Time Frame

Dec 2009

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

61 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: Age > 18 years 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 HIV-1 positivity (on 2 different rapid tests on the same blood sample) CD4 cell counts less than 250 cells/mm3 Likely to remain in the same area for at least two years after start of treatment. 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). Willingness for home visits, and to attend for investigations, supervised treatment and follow-up as required. Within the area of intake (25 kms from any of the TRC subcentres). Willingness to use contraception during trial period. 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 (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. Serious cardiac disease (CCF, IHD), uncontrolled diabetes mellitus, cancer, moribund state Previous antituberculosis treatment for more than 1 month. Previous antiretroviral treatment for more than 1 month Patients with CD4 cell count >250 cells/mm3. HIV-2 infection alone or in combination with HIV-1. Patients currently using alcohol, IV drugs & other substance abuse. Unwilling to use contraception & avoid pregnancy. Unwilling to HIV/TB screening and participation in trial.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Soumya Swaminathan, MD

Organizational Affiliation

Tuberculosis Research Centre, India

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

PR Narayanan, PhD

Organizational Affiliation

Tuberculosis Research Centre, India

Official's Role

Study Director

Facility Information:

Facility Name

Tuberculosis Research Centre

City

Chennai

State/Province

Tamilnadu

ZIP/Postal Code

600031

Country

India

12. IPD Sharing Statement

Citations:

PubMed Identifier

15220699

Citation

Jack C, Lalloo U, Karim QA, Karim SA, El-Sadr W, Cassol S, Friedland G. A pilot study of once-daily antiretroviral therapy integrated with tuberculosis directly observed therapy in a resource-limited setting. J Acquir Immune Defic Syndr. 2004 Aug 1;36(4):929-34. doi: 10.1097/00126334-200408010-00006.

Results Reference

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PubMed Identifier

15319677

Citation

Patel A, Patel K, Patel J, Shah N, Patel B, Rani S. Safety and antiretroviral effectiveness of concomitant use of rifampicin and efavirenz for antiretroviral-naive patients in India who are coinfected with tuberculosis and HIV-1. J Acquir Immune Defic Syndr. 2004 Sep 1;37(1):1166-9. doi: 10.1097/01.qai.0000135956.96166.f0.

Results Reference

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PubMed Identifier

11878406

Citation

Maggiolo F, Migliorino M, Maserati R, Pan A, Rizzi M, Provettoni G, Rizzi L, Suter F; Once Study Group. Virological and immunological responses to a once-a-day antiretroviral regimen with didanosine, lamivudine and efavirenz. Antivir Ther. 2001 Dec;6(4):249-53.

Results Reference

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PubMed Identifier

12700451

Citation

Landman R, Schiemann R, Thiam S, Vray M, Canestri A, Mboup S, Kane CT, Delaporte E, Sow PS, Faye MA, Gueye M, Peytavin G, Dalban C, Girard PM, Ndoye I; Imea 011/ANRS 12-04 Study Group. Once-a-day highly active antiretroviral therapy in treatment-naive HIV-1-infected adults in Senegal. AIDS. 2003 May 2;17(7):1017-22. doi: 10.1097/00002030-200305020-00010.

Results Reference

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PubMed Identifier

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Citation

Burman WJ, Jones BE. Treatment of HIV-related tuberculosis in the era of effective antiretroviral therapy. Am J Respir Crit Care Med. 2001 Jul 1;164(1):7-12. doi: 10.1164/ajrccm.164.1.2101133. No abstract available.

Results Reference

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Citation

J. M. Molina, S Perusat, F Ferchal, C Rancinan, F raffi, W Rozenbaum, D Sereni, P Morlat, G Chene and the Montana Study Group: Once-Daily Combination Therapy with Emtricitabine, Didanosine and Efavirenz in Treatment-Naïve HIV-Infected Adults: 64-week Follow-Up of the ANRS 091 Trial.

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PubMed Identifier

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Citation

Ribera E, Pou L, Lopez RM, Crespo M, Falco V, Ocana I, Ruiz I, Pahissa A. Pharmacokinetic interaction between nevirapine and rifampicin in HIV-infected patients with tuberculosis. J Acquir Immune Defic Syndr. 2001 Dec 15;28(5):450-3. doi: 10.1097/00042560-200112150-00007.

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PubMed Identifier

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Citation

Narendran G, Menon PA, Venkatesan P, Vijay K, Padmapriyadarsini C, Ramesh Kumar S, Bhavani KP, Sekar L, Gomathi SN, Chandrasekhar C, Kumar S, Sridhar R, Swaminathan S. Acquired rifampicin resistance in thrice-weekly antituberculosis therapy: impact of HIV and antiretroviral therapy. Clin Infect Dis. 2014 Dec 15;59(12):1798-804. doi: 10.1093/cid/ciu674. Epub 2014 Aug 25.

Results Reference

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Citation

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Results Reference

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Links:

URL

http://www.icmr.nic.in

Description

Indian Council of Medical Research

URL

http://www.nacoonline.org/NACO

Description

National AIDS Control Organisation

Tuberculosis, Human Immunodeficiency Virus Infections

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial