Treatment Duration for Abdominal Tuberculosis

Tuberculosis Clinical Trial

— RNTCP-DOTS  

Official title:

A Multi-centric Study on Treatment of Abdominal Tuberculosis (Intestinal or Peritoneal): A Randomized Controlled Trial to Compare the 6 Months of Cat I Treatment With 9 Months of Cat I Treatment (Extension for 3 Months) in Abdominal Tuberculosis Under the Revised National Tuberculosis Control Program

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01124929
• Other study ID #: Abdominal TB_RCT (RNTCP-DOTS)
• Status: Completed
• Phase: Phase 3
• First received: May 3, 2010
• Last updated: July 2, 2015
• Start date: July 2008
• Est. completion date: April 2014

Study information

• Verified date: July 2015
• Source: All India Institute of Medical Sciences, New Delhi
• Contact: n/a
• Is FDA regulated: No
• Health authority: India: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Most of the guidelines on the treatment of tuberculosis suggest that 6 months treatment is sufficient for extrapulmonary tuberculosis except for bone tuberculosis and tubercular meningitis. Despite these recommendations, most physicians treating abdominal tuberculosis use antituberculous therapy for 9 months, sometimes even 12 months without any scientific justification. In a randomized controlled trial, Balasubramaniam et al reported no difference in success rate of 6mo (99%) vs 12 months (94%) antituberculous drugs (conventional strategy) in the treatment of abdominal tuberculosis.

Although Directly Observed Therapy (DOTs) have been proved to be effective in patients with pulmonary tuberculosis, lymph nodal tuberculosis, however, there is a lack of data on efficacy of DOTS in other extra-pulmonary disease including abdominal tuberculosis. Therefore, there is an urgent need to establish the efficacy of DOTs strategy of antituberculous therapy in the treatment of abdominal tuberculosis.

Therefore, the investigators planned to conduct a multicenter randomized controlled trial to determine the difference in the recurrence of disease after only observation for three months and three months extension of DOTs in a subset of patients with definite clinical response after 6 months of DOTs.

Description:

Rationale Most of the guidelines on the treatment of tuberculosis suggest that 6 months treatment is sufficient for extrapulmonary tuberculosis except for bone tuberculosis and tubercular meningitis. Despite these recommendations, most physicians treating abdominal tuberculosis use antituberculous therapy for 9 months, sometimes even 12 months without any scientific justification. In a randomized controlled trial, Balasubramaniam et al reported no difference in success rate of 6mo (99%) vs 12 months (94%) antituberculous drugs (conventional strategy) in the treatment of abdominal tuberculosis.

Although DOTS have been proved to be effective in patients with pulmonary tuberculosis, lymph nodal tuberculosis, however, there is a lack of data on efficacy of DOTS in other extra-pulmonary disease including abdominal tuberculosis. The aim of the present study is not to assess the efficacy of DOTs but whether the Cat I regimen for 6 months is effective in the treatment of abdominal tuberculosis. We, therefore planned to conduct a multicenter randomized controlled trial to determine the difference in the efficacy and recurrence rate in 6months and 9 months of intermittent short course category I regimen under RNTCP.

Hypothesis There may not be a significant difference in the efficacy and recurrence rate of abdominal tuberculosis in those treated for six months vs those treated for 9 months with intermittent short course category I regimen under RNTCP.

Objectives

Primary objectives:

1. To determine the efficacy of intermittent short course chemotherapy for 6 months under Directly Observed Therapy (Category I under RNTCP) in treatment of abdominal tuberculosis (proportion of patients responding to treatment)

2. To determine difference in the recurrence of disease between the two randomized groups after only observation for three months and extension of RNTCP Cat I for three months in a subset of patients with definite clinical response after 6 months of DOTs Secondary objective

1. To study the effect of anti-tubercular drugs on the natural history of intestinal stricture due to tuberculosis Outcomes

Outcome measures:

Primary:

1. Response to treatment (6 months and nine months of RNTCP Cat I treatment) as defined earlier

2. Recurrence of symptoms of abdominal tuberculosis (intestinal and peritoneal) after 1 year of follow up in those who receive 6 months or 9 months of Cat I treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 197
• Est. completion date: April 2014
• Est. primary completion date: July 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion criteria:

• Newly diagnosed patients with Intestinal TB or Peritoneal TB

• Has not received ATT for Tuberculosis any where in the body during past 5 years

• Patients having good general health and not too sick.

• Patients willing and likely to comply with the study procedures and follow up

• Patients should give informed consent.

Exclusion Criteria:

• Eighteen year is a cut off age for definition of adult and pediatric and adolescent medicine. The dosing of drugs are different in these two age groups. Therefore we plan to include patients of more than 18 years of age with abdominal TB in this study.

• Intake of ATT during the past 5 years

• Doubtful diagnosis

• Crohn's disease

• Patients with HIV and AIDS may have another systemic opportunistic infections including GI infections like cryptosporidiosis, Microsporidiosis or isosporiasis. There may be an overlap of GI manifestations such as diarrhea, abdominal pain, anemia, fever. Therefore, assessment of response to anti-tuberculosis therapy may be blurred. In order to keep the study group homogenous for comparison, we plan to exclude all those with HIV infection

• Chronic Liver Disease

• Associated significant co-morbidities

• H/O Sensitivity

• Peritoneal carcinomatosis

• Patients must not been used investigational agents during the past 6 months

• Unwilling patient

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Drug:
• RNTCP Category I treatment for 6 months
2H3R3Z3 E3 + 4H3R3
• RNTCP Category I treatment for 9months
2H3R3Z3 E3 + 7H3R3

Locations

Country	Name	City	State
India	Dr Govind K Makharia	New Delhi	Delhi

Sponsors (3)

Lead Sponsor	Collaborator
All India Institute of Medical Sciences, New Delhi	Christian Medical College, Vellore, India, Sanjay Gandhi Postgraduate Institute of Medical Sciences

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response to treatment (after 6 months and nine months of RNTCP Category I treatment)	Intestinal tuberculosis: Complete response to treatment: Resolution of clinical manifestations, Healing of demonstrable lesions, Microbiological response (Conversion of positive to negative); Clinical failure: Failure of response to treatment: Persistence of clinical manifestations Persistence of morphological lesions; Peritoneal tuberculosis: Definition for response Complete response: Complete resolution of ascites within 6 months No response: Persistence of ascites	1 year	No
Primary	Recurrence of symptoms of abdominal tuberculosis (intestinal and peritoneal) after 1 year of follow up in those who receive 6 months or 9 months of Cat I treatment		1 year	No