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Sponsors and Collaborators: |
All India Institute of Medical Sciences, New Delhi Ministry of Health and Family Welfare, Govt. of India |
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Information provided by: | All India Institute of Medical Sciences, New Delhi |
ClinicalTrials.gov Identifier: | NCT00698334 |
Tuberculosis (TB) is the most common opportunistic infection among HIV infected persons living in developing countries. Directly observed treatment, short-course (DOTS) is the internationally recommended strategy for the treatment of TB. However, the efficacy of DOTS for the treatment of HIV-associated TB is not well studied. This study aims to compare the efficacy of thrice weekly DOTS in HIV-infected versus HIV-negative patients with TB.
Condition | Intervention | Phase |
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HIV Infections Acquired Immunodeficiency Syndrome Tuberculosis |
Drug: INH, Rifampicin, Ethambutol and Pyrazinamide |
Phase III |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study |
Official Title: | Efficacy of Thrice Weekly Intermittent Short Course Antituberculosis Chemotherapy in Tuberculosis Patients With and Without HIV Infection |
Estimated Enrollment: | 150 |
Study Start Date: | April 2006 |
Estimated Study Completion Date: | April 2009 |
Estimated Primary Completion Date: | April 2009 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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HIV infected: Experimental
HIV infected patients with active TB
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Drug: INH, Rifampicin, Ethambutol and Pyrazinamide
Directly Observed Treatment Short-course; Thrice weekly (INH 600 mg, Rifampicin 450 mg [600 mg if more than 59 kg], Ethambutol 1200 mg, Pyrazinamide 1500 mg)
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HIV negative: Active Comparator
HIV negative patients with active TB
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Drug: INH, Rifampicin, Ethambutol and Pyrazinamide
Directly Observed Treatment Short-course; Thrice weekly (INH 600 mg, Rifampicin 450 mg [600 mg if more than 59 kg], Ethambutol 1200 mg, Pyrazinamide 1500 mg)
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Several reports have suggested that the initial response to antituberculosis chemotherapy is comparable among HIV-positive and negative populations.
These series generally demonstrate that among "surviving" Patients, the bacteriological, clinical, and radiographic responses are similar between the two groups. However, there are consistent indications of higher rates of early (first month) deaths from tuberculosis as well as excessive deaths from other causes during the course of treatment in the above noted series. These deaths appear related to the advanced stage of tuberculosis at diagnosis as well as the debilitating and underlying diseased from which the patients suffer and not primarily the drug regimens with which they are treated. However, several of the reports from Africa suggested increased early mortality in those who received the less-potent traditional isoniazid, thiacetazone, and streptomycin regimens than the modern short-course regimens featuring isoniazid, rifampin, and pyrazinamide. Excess mortality was seen also among a subset of patients with AIDS and tuberculosis in Uganda receiving a thiacetazone regimen in comparison to those receiving a rifampin regimen: there was both excess mortality and higher rates of drug reactions sequestered among those patients who had elevated levels of neopterin and other markers of cellular immune activation.
Furthermore, several series have shown a modestly greater risk for relapse or recurrence post treatment for persons with AIDS that seems related to the duration of therapy. Perriens and colleagues in a study from Zaire compared the outcome of HIV-positive patients treated with 6-month regimen (2-HRZE daily followed by 10-HR twice weekly) and a 12-month regimen (2-HRZE daily followed by 10-HR twice weekly). Relapse rates were significantly higher among those receiving the 6-months regimen (9%) than 12 months of treatment (1.9%) (p < 0.01). Pulido and colleagues in Spain observed in a non-randomize series that, among patients with AIDS and tuberculosis, 10 of 40 (24%) patients who received less than 9-months or more did so.
Multivariate analysis identified duration of therapy as a major element in the disparate relapse rates, with a relative hazard of 9.2 for the shorter-duration therapy. Most recently, a multicenter national trial in the United States compared 6-month and 9-month of treatment for HIV-infected adults with pansusceptible tuberculosis. Relapse rates were 3.9%, two patients, for the 6-month regimen, and 2%, one patient, for the 9-month regimen; because of the limited number, there was no statistically significant difference.
Several other studies contrasted relapse or cure rates among HIV infected and uninfected persons treated simultaneously with identical 6-month regimens.
They universally showed somewhat worse outcomes among those with HIV infection.
Hawkens and colleagues described and increased risk of recurrent tuberculosis in a group of patients from Kenya. This report documented that 10 of 58 (17%) HIV Positive patients available for follow-up had recurrence, contrasted with 1 of 138 HIV negative patients, 34-fold apparent relative risk.
However, 7 of the 10 who experienced recurrence had major cutaneous drug reactions, interrupting therapy and confounding the issue. But, Elliott in Zambia noted a marked disparity in relapse rates without the confusing association between relapses and drug reactions: HIV-positive patients relapsed at a rate 22-100 patient years of observation versus 6/100 patient years among HIV-negatives. A recent Johns Hopkins study in Haiti found lower cure rates (69% vs. 79%) and slightly higher relapse rates (5.4% vs. 2.8%, p = 0.36) among HIV-infected individuals receiving a 6-month regimen.
Ages Eligible for Study: | 18 Years to 60 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Surendra K Sharma, MD. Ph.D | 26-594-415 | surensk@gmail.com, sksharma@aiims.ac.in |
Contact: Sanjeev Sinha, MD | 26-594-440 | sanjusinha@hotmail.com |
India | |
All India Institute of Medcial Sciences | Recruiting |
New Delhi, India, 110029 | |
Contact: Surendra K Sharma, MD, Ph.D 26-594-415 surensk@gmail.com, sksharma@aiims.ac.in | |
Contact: Sanjeev Sinha, MD 26-594-440 sanjusinha@hotmail.com | |
Principal Investigator: Surendra K Sharma, MD, Ph.D | |
Sub-Investigator: Sanjeev Sinha, MD | |
Sub-Investigator: Urvashi B Singh, MD, Ph.D | |
Sub-Investigator: Pranay K Sinha, MD |
Principal Investigator: | Surendra K Sharma, MD. Ph.D | All India Institute of Medical Sciences, New Delhi |
Responsible Party: | All India Institute of Medical Sciences ( Dr. S.K. Sharma, Professor & Head ) |
Study ID Numbers: | SKS/NACO/2006 |
Study First Received: | June 10, 2008 |
Last Updated: | June 16, 2008 |
ClinicalTrials.gov Identifier: | NCT00698334 History of Changes |
Health Authority: | India: Ministry of Health |
HIV infection Acquired immunodeficiency syndrome Tuberculosis |
Bacterial Infections Sexually Transmitted Diseases, Viral Acquired Immunodeficiency Syndrome Pyrazinamide Immunologic Deficiency Syndromes Virus Diseases Anti-Bacterial Agents Rifampin |
Gram-Positive Bacterial Infections HIV Infections Sexually Transmitted Diseases Mycobacterium Infections Tuberculosis Ethambutol Antitubercular Agents Retroviridae Infections |
Bacterial Infections Anti-Infective Agents Communicable Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Molecular Mechanisms of Pharmacological Action Infection Anti-Bacterial Agents Rifampin Gram-Positive Bacterial Infections Pathologic Processes Therapeutic Uses Syndrome Tuberculosis Retroviridae Infections |
Nucleic Acid Synthesis Inhibitors RNA Virus Infections Disease Immune System Diseases Acquired Immunodeficiency Syndrome Enzyme Inhibitors Pyrazinamide Pharmacologic Actions Immunologic Deficiency Syndromes Actinomycetales Infections Antibiotics, Antitubercular Virus Diseases HIV Infections Sexually Transmitted Diseases Lentivirus Infections |