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

NCT00933790 | Completed Phase 3 DMC

• 1 other identifier: TRC25
• Study Type: interventional
• Target: 331
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

HIV Infection; Pulmonary TB

Keywords

TB; HIV; ARR; Short course chemotherapy; Drug resistance

Outcome Measures

Primary Outcomes (1)

• unfavourable responses during treatment

  including bacteriological and failures and ARR, clinical failures, TEADRS requiring premanent discontinuation of the drug , Deaths except unnatural and Defaults during treatment period

  At the end of 6 months

Secondary Outcomes (3)

• Unfavorable responses during follow-up

  At the end of 6 months and at the end of follow-up of 1 year

• TEADR's between the groups

  At the end of 6 months and at the end of follow-up of 1 year

• Incidence of Immune Reconstitution Syndrome among the groups

  At the end of 6 months and at the end of follow-up of 1 year

Study Arms (3)

2EHRZ3/4HR3

ACTIVE COMPARATOR

Regimen 3. Intermittent - 2EHRZ3/4HR3 (E 1200mg, H 600 mg, R 450/600 mg depending on Weight \<60, 600 mg for 60 kg or more, Z 1500 mg given thrice weekly)

Drug: ATT (Ethambutol, Pyrazinamide, INH, Rifampicin)

2EHRZ7/4HR7

EXPERIMENTAL

Regimen 1. Daily - 2EHRZ7/4HR7 (E 800 mg ,H 300 mg, R 450/600 mg depending on Weight \<60, 600 mg for 60 kg or more, Z 1500 mg daily)

Drug: ATT (Ethambutol, Pyrazinamide, INH, Rifampicin)

2EHRZ7/4HR3

EXPERIMENTAL

Regimen 2. Part Daily - 2EHRZ7/4HR3 (E 800 mg ,H 300 mg, R 450/600 mg depending on Weight \<60, 600 mg for 60 kg or more, Z 1500 mg daily in the intensive phase followed by H-600 mg ,R-450/600 mg in the continuation phase thrice weekly)

Drug: ATT (Ethambutol, Pyrazinamide, INH, Rifampicin)

Interventions

ATT (Ethambutol, Pyrazinamide, INH, Rifampicin) DRUG

Ethambutol 800 mg for daily, 1200 mg for intermittent therapy, Pyrazinamide 1500 mg for both daily and intermittent, INH 300 mg for daily and 600 mg for intermittent therapy, Rifampicin 450 mg for both daily and intermittent therapy for patients below 60 kg, 600 mg for both daily and intermittent therapy for patients 60 kg and above

Also known as: ATT, Rifampicin

2EHRZ3/4HR3; 2EHRZ7/4HR3; 2EHRZ7/4HR7

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age above 18 years.
• HIV-1/2 infected patients with Pulmonary TB. This includes sputum smear positive disease.
• Living within 40 km radius from the nearest sub centre of TRC and willing for attendance as prescribed.
• Likely to remain in the same area for at least one and half years after start of treatment.
• Willing for house visits and surprise checks.
• Willing to participate and give informed consent after going through the terms and conditions of the trial.

You may not qualify if:

• Patients with known hypersensitivity to rifampicin
• Pregnancy and lactation at initial presentation
• Major complications like HIV encephalopathy, renal dysfunction (serum creatinine \> 1.5 mg% in the absence of dehydration) or jaundice (serum bilirubin \> 2 mgs% along with SGOT /SGPT elevation \> 2.5 times the upper limit of normal).
• Previous anti-tuberculosis treatment for more than 1 month. Prophylaxis (non-rifampicin containing regimen) will not be considered as prior antituberculosis treatment.
• Moribund, bedridden or unconscious patients.
• Co-morbid conditions like uncontrolled diabetes mellitus, cardiac failure, and malignancy at initial presentation.
• Major psychiatric illness.
• Patients on second line ART, mainly protease inhibitors, at initial presentation.

Sponsors & Collaborators

• Tuberculosis Research Centre, India: lead

Study Sites (3)

Tuberculosis Research Centre (ICMR)

Chennai, Tamil Nadu, 600 031, India

Location

Govt. Hospital of Thoracic Medicine, Tambaram

Chennai, Tamil Nadu, 600 047, India

Location

Tuberculosis Research Centre (ICMR)

Madurai, Tamil Nadu, 625 020, India

Location

Related Publications (2)

• Tiburcio R, Barreto-Duarte B, Naredren G, Queiroz ATL, Anbalagan S, Nayak K, Ravichandran N, Subramani R, Antonelli LRV, Satagopan K, Anbalagan K, Porter BO, Sher A, Swaminathan S, Sereti I, Andrade BB. Dynamics of T-Lymphocyte Activation Related to Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in Persons With Advanced HIV. Front Immunol. 2021 Oct 7;12:757843. doi: 10.3389/fimmu.2021.757843. eCollection 2021.

  PMID: 34691079 DERIVED

• Gopalan N, Santhanakrishnan RK, Palaniappan AN, Menon PA, Lakshman S, Chandrasekaran P, Sivaramakrishnan GN, Reddy D, Kannabiran BP, Agiboth HKK, Krishnamoorthy V, Rathinam S, Chockalingam C, Manoharan T, Ayyamperumal M, Jayanthi N, Satagopan K, Narayanan R, Krishnaraja R, Sathiyavelu S, Kesavamurthy B, Suresh C, Selvachitiram M, Arasan G, Susaimuthu S, Rathinam P, Angamuthu P, Jayabal L, Murali L, Ramachandran R, Tripathy SP, Swaminathan S. Daily vs Intermittent Antituberculosis Therapy for Pulmonary Tuberculosis in Patients With HIV: A Randomized Clinical Trial. JAMA Intern Med. 2018 Apr 1;178(4):485-493. doi: 10.1001/jamainternmed.2018.0141.

  PMID: 29507938 DERIVED

MeSH Terms

Conditions

HIV Infections; Tuberculosis, Pulmonary

Interventions

Ethambutol; Pyrazinamide; Isoniazid; Rifampin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; 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; Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Ethylenediamines; Diamines; Polyamines; Amines; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrazines; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Narendran Gopalan, DNB (Chest)

  Scientist 'B', Tuberculosis Research Centre (ICMR), Chennai, India

  PRINCIPAL INVESTIGATOR

• Soumya Swaminathan, MD

  Scientist 'F', Tuberculosis Research Centre (ICMR), Chennai, India

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Asst.Director, NIRT

Study Record Dates

• First Submitted: July 3, 2009
• First Posted: July 7, 2009
• Study Start: September 14, 2009
• Primary Completion: December 31, 2016
• Study Completion: June 30, 2018
• Last Updated: April 10, 2019

Record last verified: 2019-04

Locations

IN (3)