Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

June 10, 2008
November 5, 2011
April 2006
September 2010   (final data collection date for primary outcome measure)
Cure rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00698334 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Efficacy of Thrice Weekly Directly Observed Treatment, Short-course (DOTS) in HIV-associated Tuberculosis
Efficacy of Thrice Weekly Intermittent Short Course Antituberculosis Chemotherapy in Tuberculosis Patients With and Without HIV Infection

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.

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.

Interventional
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV Infections
  • Acquired Immunodeficiency Syndrome
  • Tuberculosis
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
  • Experimental: HIV infected
    HIV infected patients with active TB
    Intervention: Drug: INH, Rifampicin, Ethambutol and Pyrazinamide
  • Active Comparator: HIV negative
    HIV negative patients with active TB
    Intervention: Drug: INH, Rifampicin, Ethambutol and Pyrazinamide
Vashishtha R, Mohan K, Singh B, Devarapu SK, Sreenivas V, Ranjan S, Gupta D, Sinha S, Sharma SK. Efficacy and safety of thrice weekly DOTS in tuberculosis patients with and without HIV co-infection: an observational study. BMC Infect Dis. 2013 Oct 7;13:468. doi: 10.1186/1471-2334-13-468.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
150
April 2011
September 2010   (final data collection date for primary outcome measure)

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
Both
18 Years to 60 Years
No
Contact information is only displayed when the study is recruiting subjects
India
 
NCT00698334
SKS/NACO/2006
No
S.K.SHARMA, All India Institute of Medical Sciences, New Delhi
All India Institute of Medical Sciences, New Delhi
Ministry of Health & Family Welfare, India
Principal Investigator: Surendra K Sharma, MD. Ph.D All India Institute of Medical Sciences, New Delhi
All India Institute of Medical Sciences, New Delhi
November 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP