High-Dose Isoniazid Adjuvant Therapy for Multidrug Resistant Tuberculosis

Tuberculosis, Multidrug-Resistant Clinical Trial

Official title:

A Randomized Control Trial Of High-Dose Isoniazid Adjuvant Therapy For Multidrug Resistant Tuberculosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00513396
• Other study ID #: TB chest - 1/2005
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: August 6, 2007
• Last updated: August 6, 2007
• Start date: January 2004
• Est. completion date: December 2006

Study information

• Verified date: July 2007
• Source: GSVM Medical College
• Contact: n/a
• Is FDA regulated: No
• Health authority: India: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 134
• Est. completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Tuberculosis
• Tuberculosis, Multidrug-Resistant

Intervention

Drug:
• Isoniazid
High-dose isoniazid (16-18 mg/kg/day) in addition to standardized regimen that included the following: kanamycin (15 mg/kg/day), levofloxacin (7.5-15 mg/kg/day), protionamide (10-20 mg/kg/day), cycloserine (10-20 mg/kg/day) and p-aminosalicylic acid (150 mg/kg/day) Regular dose isoniazid (5 mg/kg/day) in addition to standard regimen that included the following: kanamycin (15 mg/kg/day), levofloxacin (7.5-15 mg/kg/day), protionamide (10-20 mg/kg/day), cycloserine (10-20 mg/kg/day) and p-aminosalicylic acid (150 mg/kg/day)
• Placebo
Similar appearing and similarly packaged placebo tablets in addition to the standardized regimen that included the following: kanamycin (15 mg/kg/day), levofloxacin (7.5-15 mg/kg/day), protionamide (10-20 mg/kg/day), cycloserine (10-20 mg/kg/day) and p-aminosalicylic acid (150 mg/kg/day)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
GSVM Medical College

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to sputum culture conversion		1 year
Secondary	Extent of radiological improvement		1 year
Secondary	Proportion with peripheral neuropathy		1 year
Secondary	Proportion with hepatotoxicity		1 year