Comparing Daily vs Intermittent Regimen of ATT in HIV With Pulmonary Tuberculosis
This study is ongoing, but not recruiting participants.
Sponsor:
Tuberculosis Research Centre, India
Information provided by (Responsible Party):
Narendran Gopalan, Tuberculosis Research Centre, India
ClinicalTrials.gov Identifier:
NCT00933790
First received: July 3, 2009
Last updated: March 21, 2016
Last verified: March 2016
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
HIV Infection Pulmonary TB |
Drug: ATT (Ethambutol, Pyrazinamide, INH, Rifampicin) |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Randomized Controlled Clinical Trial Comparing Daily Vs. Intermittent 6 - Month Short Course Chemotherapy in Reducing Failures & Emergence of Acquired Rifampicin Resistance (ARR) in Patients With HIV and Pulmonary Tuberculosis |
Resource links provided by NLM:
Further study details as provided by Tuberculosis Research Centre, India:
Primary Outcome Measures:
- Development of bacteriological failure & Emergence of acquired rifampicin resistance [ Time Frame: At the end of 6 months ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Unfavorable responses: clinical failures, recurrences and death due to TB during treatment and follow-up [ Time Frame: At the end of 6 months and at the end of follow-up of 1 year ] [ Designated as safety issue: Yes ]
- TEADR's between the groups [ Time Frame: At the end of 6 months and at the end of follow-up of 1 year ] [ Designated as safety issue: Yes ]
- Incidence of Immune Reconstitution Syndrome among the groups [ Time Frame: At the end of 6 months and at the end of follow-up of 1 year ] [ Designated as safety issue: Yes ]
| Enrollment: | 331 |
| Study Start Date: | September 2009 |
| Estimated Study Completion Date: | September 2018 |
| Estimated Primary Completion Date: | December 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: 2EHRZ3/4HR3
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)
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
Other Names:
|
|
Experimental: 2EHRZ7/4HR7
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)
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
Other Names:
|
|
Experimental: 2EHRZ7/4HR3
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)
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
Other Names:
|
Show Detailed Description
Eligibility| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Age above 18 years.
- HIV-1/2 infected patients with Pulmonary TB. This includes sputum smear positive disease.
- Initially smear negative but Xpert-MTB positive or LPA positive taken as a surrogate marker for culture positivity (e.g. miliary TB, Mediastinal adenitis and Chest x-ray with persistent abnormality after antibiotics). as BACTEC (Becton-Dickinson) has been phased out ,Final inclusion will only be patients positive by LJ culture
- Persistent X-ray abnormality will be included for allocation. However final inclusion into both ITT and efficacy analysis will depend on positivity in LJ culture.
- 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.
Exclusion Criteria:
- 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.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00933790
Please refer to this study by its ClinicalTrials.gov identifier: NCT00933790
Locations
| India | |
| Tuberculosis Research Centre (ICMR) | |
| Chennai, Tamil Nadu, India, 600 031 | |
| Govt. Hospital of Thoracic Medicine, Tambaram | |
| Chennai, Tamil Nadu, India, 600 047 | |
| Tuberculosis Research Centre (ICMR) | |
| Madurai, Tamil Nadu, India, 625 020 | |
Sponsors and Collaborators
Tuberculosis Research Centre, India
Investigators
| Principal Investigator: | 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 |
More Information
Additional Information:
| Responsible Party: | Narendran Gopalan, Asst.Director, NIRT, Tuberculosis Research Centre, India |
| ClinicalTrials.gov Identifier: | NCT00933790 History of Changes |
| Other Study ID Numbers: | TRC25 |
| Study First Received: | July 3, 2009 |
| Last Updated: | March 21, 2016 |
| Health Authority: | India: Indian Council of Medical Research |
Keywords provided by Tuberculosis Research Centre, India:
|
TB HIV ARR Short course chemotherapy Drug resistance |
Additional relevant MeSH terms:
|
HIV Infections Tuberculosis Tuberculosis, Pulmonary Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections Bacterial Infections |
Lung Diseases Respiratory Tract Diseases Respiratory Tract Infections Rifampin Pyrazinamide Ethambutol Antibiotics, Antitubercular Antitubercular Agents Anti-Bacterial Agents Anti-Infective Agents Leprostatic Agents Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Cytochrome P-450 CYP2B6 Inducers |
ClinicalTrials.gov processed this record on September 29, 2016