High-Dose Isoniazid Adjuvant Therapy for Multidrug Resistant Tuberculosis

Condition(s) targeted: Tuberculosis, Multidrug-Resistant

Intervention: Isoniazid (Drug); Placebo (Drug)

Phase: Phase 2/Phase 3

Status: Completed

Sponsored by: GSVM Medical College

Official(s) and/or principal investigator(s):
Subodh Katiyar, MD, Study Chair, Affiliation: GSVM Medical College, Kanpur, India
Shivesh Prakash, MBBS, Principal Investigator, Affiliation: GSVM Medical College, Kanpur, India
Shailesh Bihari, MD, Principal Investigator, Affiliation: GSVM Medical College, Kanpur, India
Hemant Kulkarni, MD, Principal Investigator, Affiliation: Lata Medical Research Foundation, Nagpur, India
Manju Mamtani, MD, Principal Investigator, Affiliation: Lata Medical Research Foundation, Nagpur, India

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.

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

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Time to sputum culture conversion

Secondary outcome:

Extent of radiological improvement

Proportion with peripheral neuropathy

Proportion with hepatotoxicity

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Starting date: January 2004
Ending date: December 2006
Last updated: August 6, 2007