High-Dose Isoniazid Adjuvant Therapy for Multidrug Resistant Tuberculosis
Information source: GSVM Medical College
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Tuberculosis, Multidrug-Resistant
Intervention: Isoniazid (Drug); Placebo (Drug)
Phase: Phase 2/Phase 3
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
Extent of radiological improvement
Proportion with peripheral neuropathy
Proportion with hepatotoxicity
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.
- Consecutive patients reporting to the study center
- Sputum-positive for acid-fast bacilli
- MDR-TB defined as resistance to at least the following two drugs: Isoniazid and
- Unwilling to give consent
- Abnormal renal or hepatic profile
- History suggestive of isoniazid hypersensitivity
- Lactating mother
- Previous history of taking any of the following: kanamycin, prothionamide,
levofloxacin, cycloserine and p-aminosalicylic acid
Locations and Contacts
Starting date: January 2004
Ending date: December 2006
Last updated: August 6, 2007