High-Dose Isoniazid Adjuvant Therapy for Multidrug Resistant Tuberculosis

Phase 2

Completed

• Conditions: Tuberculosis, Multidrug-Resistant
• Interventions: Drug: Isoniazid; Drug: Placebo

• Registration Number: NCT00513396
• Lead Sponsor: GSVM Medical College

Brief Summary

The need for a standardized treatment protocol for multidrug resistant tuberculosis (MDR-TB) in resource-limited countries is being increasingly recognized. This single center, double blind, randomized controlled trial was designed to compare the time required for sputum culture conversion and extent of radiological improvement in cases of MDR pulmonary tuberculosis when isoniazid was included (both at a regular dose and at a high dose) as an adjuvant to the standardized second line of treatment. The study was designed to test the hypothesis that inclusion of high-dose isoniazid will enhance the effectiveness of the second line of treatment in cases of MDR-TB without significantly increasing the toxicity.

Detailed Description

Tuberculosis was declared a global emergency by the World Health Organization (WHO) in 1993. The global problem of tuberculosis is further complicated by a substantial increase in drug resistant tuberculosis. Available data suggest that drug resistant TB especially multi drug resistant may represent a public health threat in areas with a high prevalence of tuberculosis, suboptimal TB control programmes and/ or HIV. The cure rate of these cases has been reported to be lower than for non-drug resistant TB with a failure rate of 44%. New therapies for MDR-TB have not been introduced since the fluoroquinolones in the 1970s. Strains of Mycobacterium Tuberculosis (M. tub.) in H resistant cases often contain mixture of susceptible \& resistant organisms. Use of high dose H (16- 20 mg/kg) can eliminate susceptible \& those with low level resistance4. This Study was done to evaluate the role of isoniazid (INH) at high \& normal dosages as an adjuvant therapy in treatment of patients with persistent culture positive pulmonary tuberculosis despite 6 months of continuous first line antitubercular treatment and on culture at least resistant to isoniazid and rifampicin.

Study Timeline

• Study Start: 2004-01
• Study Completion: 2006-12
• Status Verified: 2007-07
• Study First Submitted: 2007-08-06
• Study First Submitted QC: 2007-08-06
• Last Update Submitted: 2007-08-06
• Study First Posted: 2007-08-08
• Last Update Posted: 2007-08-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 134

Inclusion Criteria

• Consecutive patients reporting to the study center
• Sputum-positive for acid-fast bacilli
• HIV-uninfected
• MDR-TB defined as resistance to at least the following two drugs: Isoniazid and Rifampicin.

Exclusion Criteria

• Unwilling to give consent
• Abnormal renal or hepatic profile
• History suggestive of isoniazid hypersensitivity
• Pregnancy
• Lactating mother
• Previous history of taking any of the following: kanamycin, prothionamide, levofloxacin, cycloserine and p-aminosalicylic acid

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Isoniazid	-
2	Isoniazid	-
3	Placebo	-

Primary Outcome Measures

Name	Time	Method
Time to sputum culture conversion	1 year

Secondary Outcome Measures

Name	Time	Method
Extent of radiological improvement	1 year
Proportion with peripheral neuropathy	1 year
Proportion with hepatotoxicity	1 year