High-Dose Isoniazid Adjuvant Therapy for Multidrug Resistant Tuberculosis

NCT00513396 | Completed Phase 2

• 1 other identifier: TB chest - 1/2005
• Study Type: interventional
• Target: 134
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Tuberculosis, Multidrug-Resistant

Keywords

Randomized control trial; multidrug resistant tuberculosis; isoniazid; standardized regimen; adjuvant therapy

Outcome Measures

Primary Outcomes (1)

• Time to sputum culture conversion

  1 year

Secondary Outcomes (3)

• Extent of radiological improvement

  1 year

• Proportion with peripheral neuropathy

  1 year

• Proportion with hepatotoxicity

  1 year

Study Arms (3)

1

EXPERIMENTAL

Drug: Isoniazid

2

ACTIVE COMPARATOR

Drug: Isoniazid

3

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Isoniazid DRUG

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)

1; 2

Placebo DRUG

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)

3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• GSVM Medical College: lead

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant

Interventions

Isoniazid

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Subodh Katiyar, MD

  GSVM Medical College, Kanpur, India

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 6, 2007
• First Posted: August 8, 2007
• Study Start: January 1, 2004
• Study Completion: December 1, 2006
• Last Updated: August 8, 2007

Record last verified: 2007-07