NCT00933790

Comparing Daily vs Intermittent Regimen of ATT in HIV With Pulmonary Tuberculosis

Completed Phase 3 Last updated 10 April 2019

What this trial tests

Phase 3 trial testing ATT (Ethambutol, Pyrazinamide, INH, Rifampicin) in HIV Infection in 331 participants. Completed in 30 June 2018.

Timeline

14 September 2009

Primary endpoint
31 December 2016

30 June 2018

Quick facts

Lead sponsor	Tuberculosis Research Centre, India
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	331
Start date	14 September 2009
Primary completion	31 December 2016
Estimated completion	30 June 2018
Sites	3 locations across India

Drugs / interventions tested

• ATT (Ethambutol, Pyrazinamide, INH, Rifampicin) — full drug profile →

Conditions studied

• HIV Infection — all drugs for HIV Infection →
• Pulmonary TB — all drugs for Pulmonary TB →

Sponsor

Tuberculosis Research Centre, India — full company profile →

Who can join

18 and older, any sex, with HIV Infection or Pulmonary TB. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Acquired Rifampicin Resistance has emerged as an important issue in the treatment of HIV-TB patients. It has not been a major problem in HIV-negative individuals treated for TB treated with standard intermittent regimens. The study would generate data on the efficacy of daily and thrice weekly regimen of ATT in pulmonary TB patients with HIV in the presence of highly active antiretroviral therapy (HAART). Not many trials have compared sputum conversion and adverse drug reaction between daily and intermittent regimens of ATT in HIV positive patients. This study provides a unique opportunity for comparison of daily and intermittent therapy for HIV patients with pulmonary TB looking into multiple dimensions of HIV-TB treatment namely efficacy, drug resistance, toxicity , drug interaction and immune reconstitution inflammatory syndrome. The primary outcome of the study is to compare the efficacy of three anti-TB regimens in a) reducing bacteriological failures and b) decreasing the emergence of Acquired Rifampicin Resistance (ARR). The secondary outcomes include unfavourable responses (clinical failures, deaths, relapses) as whole, treatment emergent adverse drug reactions, pharmacokinetic levels of ATT and incidence of immune reconstitution syndrome.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Differential expression of CXCR3 and CCR6 on CD4⁺ T-lymphocytes with distinct memory phenotypes characterizes tuberculosis-associated immune reconstitution inflammatory syndrome.
   Silveira-Mattos PS, Narendran G, Akrami K, Fukutani KF, et al · · 2019 · cited 23× · PMID 30728405 · DOI 10.1038/s41598-018-37846-3
2. Daily vs Intermittent Antituberculosis Therapy for Pulmonary Tuberculosis in Patients With HIV: A Randomized Clinical Trial.
   Gopalan N, Santhanakrishnan RK, Palaniappan AN, Menon PA, et al · · 2018 · cited 22× · PMID 29507938 · DOI 10.1001/jamainternmed.2018.0141
3. Dynamics of T-Lymphocyte Activation Related to Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in Persons With Advanced HIV.
   Tibúrcio R, Barreto-Duarte B, Naredren G, Queiroz ATL, et al · · 2021 · cited 10× · PMID 34691079 · DOI 10.3389/fimmu.2021.757843
4. A systematic review of endpoint definitions in late phase pulmonary tuberculosis therapeutic trials.
   Hills NK, Lyimo J, Nahid P, Savic RM, et al · · 2021 · cited 10× · PMID 34344435 · DOI 10.1186/s13063-021-05388-1
5. Characteristics of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome and its influence on tuberculosis treatment outcomes in persons living with HIV.
   Narendran G, Jyotheeswaran K, Senguttuvan T, Vinhaes CL, et al · · 2020 · cited 5× · PMID 32623087 · DOI 10.1016/j.ijid.2020.06.097
6. Oral abstracts of the 21st International AIDS Conference 18-22 July 2016, Durban, South Africa.
   · 2016 · cited 5× · PMID 27460772 · DOI 10.7448/ias.19.6.21264
7. Frequency of CXCR3⁺ CD8⁺ T-Lymphocyte Subsets in Peripheral Blood Is Associated With the Risk of Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome Development in Advanced HIV Disease.
   Tibúrcio R, Narendran G, Barreto-Duarte B, Queiroz ATL, et al · · 2022 · cited 3× · PMID 35432354 · DOI 10.3389/fimmu.2022.873985
8. Potential hematological biosignatures as screening tools for tuberculosis co- infection among people living with HIV
   J NH, Gopalan N, VV BR, Luke EH, et al · · 2024 · DOI 10.21203/rs.3.rs-4285475/v1