High-Dose Isoniazid Adjuvant Therapy for Multidrug Resistant Tuberculosis

This study has been completed.
Sponsor:
Information provided by:
GSVM Medical College
ClinicalTrials.gov Identifier:
NCT00513396
First received: August 6, 2007
Last updated: NA
Last verified: July 2007
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Tuberculosis, Multidrug-Resistant
Drug: Isoniazid
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Control Trial Of High-Dose Isoniazid Adjuvant Therapy For Multidrug Resistant Tuberculosis

Resource links provided by NLM:


Further study details as provided by GSVM Medical College:

Primary Outcome Measures:
  • Time to sputum culture conversion [ Time Frame: 1 year ]

Secondary Outcome Measures:
  • Extent of radiological improvement [ Time Frame: 1 year ]
  • Proportion with peripheral neuropathy [ Time Frame: 1 year ]
  • Proportion with hepatotoxicity [ Time Frame: 1 year ]

Enrollment: 134
Study Start Date: January 2004
Study Completion Date: December 2006
Arms Assigned Interventions
Experimental: 1 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)

Active Comparator: 2 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 Comparator: 3 Drug: 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)

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00513396

Sponsors and Collaborators
GSVM Medical College
Investigators
Study Chair: Subodh Katiyar, MD GSVM Medical College, Kanpur, India
Principal Investigator: Shivesh Prakash, MBBS GSVM Medical College, Kanpur, India
Principal Investigator: Shailesh Bihari, MD GSVM Medical College, Kanpur, India
Principal Investigator: Hemant Kulkarni, MD Lata Medical Research Foundation, Nagpur, India
Principal Investigator: Manju Mamtani, MD Lata Medical Research Foundation, Nagpur, India
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00513396     History of Changes
Other Study ID Numbers: TB chest - 1/2005
Study First Received: August 6, 2007
Last Updated: August 6, 2007
Health Authority: India: Institutional Review Board

Keywords provided by GSVM Medical College:
Randomized control trial
multidrug resistant tuberculosis
isoniazid
standardized regimen
adjuvant therapy

Additional relevant MeSH terms:
Tuberculosis
Tuberculosis, Multidrug-Resistant
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Isoniazid
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents

ClinicalTrials.gov processed this record on August 18, 2014