Treatment Duration for Abdominal Tuberculosis

NCT ID: NCT01124929

Last Updated: 2015-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 197 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2014-04-30

Brief 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.

Detailed 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.

Conditions

Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Arm 1: Category I treatment for 6 months

Anti-tuberculosis drugs

Group Type: ACTIVE_COMPARATOR

RNTCP Category I treatment for 6 months

Intervention Type: DRUG

2H3R3Z3 E3 + 4H3R3

Arm 2: Category I treatment for 9 months

Anti-tuberculosis drugs,

Group Type: ACTIVE_COMPARATOR

RNTCP Category I treatment for 9months

Intervention Type: DRUG

2H3R3Z3 E3 + 7H3R3

Interventions

RNTCP Category I treatment for 6 months

2H3R3Z3 E3 + 4H3R3

Intervention Type: DRUG

RNTCP Category I treatment for 9months

2H3R3Z3 E3 + 7H3R3

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Sanjay Gandhi Postgraduate Institute of Medical Sciences

OTHER_GOV

Sponsor Role: collaborator

Christian Medical College, Vellore, India

OTHER

Sponsor Role: collaborator

All India Institute of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Govind K Makharia

Additional Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dr Govind K Makharia, MD, DM, DNB

Role: PRINCIPAL_INVESTIGATOR

All India Institute of Medical Sciences

Locations

Dr Govind K Makharia

New Delhi, National Capital Territory of Delhi, India

Countries

India

References

Makharia GK, Ghoshal UC, Ramakrishna BS, Agnihotri A, Ahuja V, Chowdhury SD, Gupta SD, Mechenro J, Mishra A, Mishra A, Pathak MK, Pandey RM, Sharma R, Sharma SK. Intermittent Directly Observed Therapy for Abdominal Tuberculosis: A Multicenter Randomized Controlled Trial Comparing 6 Months Versus 9 Months of Therapy. Clin Infect Dis. 2015 Sep 1;61(5):750-7. doi: 10.1093/cid/civ376. Epub 2015 May 12.

Reference Type: DERIVED

PMID: 25969531 (View on PubMed)

Other Identifiers

Abdominal TB_RCT (RNTCP-DOTS)

Identifier Type: -

Identifier Source: org_study_id