Clinical trial NCT00513396: High-Dose Isoniazid Adjuvant Therapy for Multidrug Resistant Tuberculosis
Official title: A Randomized Control Trial Of High-Dose Isoniazid Adjuvant Therapy For Multidrug Resistant Tuberculosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Tuberculosis, Multidrug-Resistant
Keywords: Randomized control trial
multidrug resistant tuberculosis
isoniazid
standardized regimen
adjuvant therapy
Lead sponsor: GSVM Medical College
Sponsor class: OTHER
First posted: 2007-08-08
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Time to sputum culture conversion
timeFrame: 1 year
Secondary outcomes:
measure: Extent of radiological improvement
timeFrame: 1 year
measure: Proportion with peripheral neuropathy
timeFrame: 1 year
measure: Proportion with hepatotoxicity
timeFrame: 1 year
Other outcomes:
Locations:
Study officials:
affiliation: GSVM Medical College, Kanpur, India
name: Subodh Katiyar, MD
role: STUDY_CHAIR
affiliation: GSVM Medical College, Kanpur, India
name: Shivesh Prakash, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: GSVM Medical College, Kanpur, India
name: Shailesh Bihari, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lata Medical Research Foundation, Nagpur, India
name: Hemant Kulkarni, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lata Medical Research Foundation, Nagpur, India
name: Manju Mamtani, MD
role: PRINCIPAL_INVESTIGATOR
References: