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

NCT00332306 | Unknown Phase 3 DMC

• 1 other identifier: trc23
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

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.

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

Conditions

Tuberculosis; Human Immunodeficiency Virus Infections

Keywords

Once daily antiretroviral treatment; Concomitant antituberculosis treatment; HIV Infections

Outcome Measures

Primary Outcomes (1)

• 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

  Dec 2008

Secondary Outcomes (2)

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

  Dec 2009

• To compare the tolerability and toxicity attributable to study drugs.

  Dec 2009

Study Arms (2)

2

EXPERIMENTAL

Didanosine + Lamivudine + Nevirapine

Drug: Didanosine, Lamivudine, Nevirapine

1

ACTIVE COMPARATOR

Didanosine + Lamivudine + Efavirenz

Drug: Didanosine, Lamivudine, Efavirenz

Interventions

Didanosine, Lamivudine, Efavirenz DRUG

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

1

Didanosine, Lamivudine, Nevirapine DRUG

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

2

Eligibility Criteria

• Age: 18 Years - 61 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tuberculosis Research Centre, India: lead
• National AIDS Control Organisation: collaborator
• Indian Council of Medical Research: collaborator

Study Sites (1)

Tuberculosis Research Centre

Chennai, Tamil Nadu, 600031, India

Location

Related Publications (9)

• 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.

  PMID: 15220699 BACKGROUND

• 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.

  PMID: 15319677 BACKGROUND

• 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.

  PMID: 11878406 BACKGROUND

• 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.

  PMID: 12700451 BACKGROUND

• 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.

  PMID: 11435232 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 11744833 BACKGROUND

• 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.

  PMID: 25156114 DERIVED

• Swaminathan S, Padmapriyadarsini C, Venkatesan P, Narendran G, Ramesh Kumar S, Iliayas S, Menon PA, Selvaraju S, Pooranagangadevi NP, Bhavani PK, Ponnuraja C, Dilip M, Ramachandran R. Efficacy and safety of once-daily nevirapine- or efavirenz-based antiretroviral therapy in HIV-associated tuberculosis: a randomized clinical trial. Clin Infect Dis. 2011 Oct;53(7):716-24. doi: 10.1093/cid/cir447.

  PMID: 21890776 DERIVED

MeSH Terms

Conditions

Tuberculosis; HIV Infections

Interventions

Didanosine; Lamivudine; efavirenz; Nevirapine

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Inosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Pyridines

Study Officials

• Soumya Swaminathan, MD

  Tuberculosis Research Centre, India

  PRINCIPAL INVESTIGATOR

• PR Narayanan, PhD

  Tuberculosis Research Centre, India

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: May 30, 2006
• First Posted: June 1, 2006
• Study Start: June 1, 2006
• Primary Completion: June 1, 2009
• Study Completion: December 1, 2011
• Last Updated: October 8, 2009

Record last verified: 2009-01

Locations

IN (1)