Efficacy of Thrice Weekly Directly Observed Treatment, Short-course (DOTS) in HIV-associated Tuberculosis

This study has been completed.
Sponsor:
Collaborator:
Ministry of Health & Family Welfare, India
Information provided by (Responsible Party):
S.K.SHARMA, All India Institute of Medical Sciences, New Delhi
ClinicalTrials.gov Identifier:
NCT00698334
First received: June 10, 2008
Last updated: November 5, 2011
Last verified: November 2011
  Purpose

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
HIV Infections
Acquired Immunodeficiency Syndrome
Tuberculosis
Drug: INH, Rifampicin, Ethambutol and Pyrazinamide
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy of Thrice Weekly Intermittent Short Course Antituberculosis Chemotherapy in Tuberculosis Patients With and Without HIV Infection

Resource links provided by NLM:


Further study details as provided by All India Institute of Medical Sciences, New Delhi:

Primary Outcome Measures:
  • Cure rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Treatment failure [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Death [ Time Frame: 12 monts ] [ Designated as safety issue: No ]
  • Relapse [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Adverse drug reactions [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 150
Study Start Date: April 2006
Study Completion Date: April 2011
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HIV infected
HIV infected patients with active TB
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)
Other Name: Category I DOTS
Active Comparator: HIV negative
HIV negative patients with active TB
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)
Other Name: Category I DOTS

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients of either gender between 18-65 years of age
  • All HIV positive and HIV negative patients suffering from confirmed tuberculosis (Cat I) will be included in the study
  • Able to give written informed consent

Exclusion Criteria:

  • Patients already started on ATT for more than two weeks except when sputum smear positive with on going ATT
  • Pregnancy
  • Patients with SGOT/SGPT levels more than three times the upper limit of normal on three occasions, five times on one occasion.
  • Serious form of pulmonary and extrapulmonary tuberculosis
  • Concomitant diabetes mellitus
  • Epilepsy
  • Alcoholics
  • Terminally ill patients
  • Defaulters
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00698334

Locations
India
All India Institute of Medcial Sciences
New Delhi, India, 110029
Sponsors and Collaborators
All India Institute of Medical Sciences, New Delhi
Ministry of Health & Family Welfare, India
Investigators
Principal Investigator: Surendra K Sharma, MD. Ph.D All India Institute of Medical Sciences, New Delhi
  More Information

No publications provided by All India Institute of Medical Sciences, New Delhi

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: S.K.SHARMA, Professor and Head, All India Institute of Medical Sciences, New Delhi
ClinicalTrials.gov Identifier: NCT00698334     History of Changes
Other Study ID Numbers: SKS/NACO/2006
Study First Received: June 10, 2008
Last Updated: November 5, 2011
Health Authority: India: Ministry of Health

Keywords provided by All India Institute of Medical Sciences, New Delhi:
HIV infection
Acquired immunodeficiency syndrome
Tuberculosis

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Tuberculosis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Ethambutol
Pyrazinamide
Rifampin
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antitubercular
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 18, 2014