Brief Bactericidal Activity of Anti-Tuberculosis Drugs (BBA)

October 13, 2020 updated by: Centers for Disease Control and Prevention

Brief Bactericidal Activity of Anti-Tuberculosis Drugs in Drug-Resistant Tuberculosis

The investigators will determine the bactericidal activity of high-dose isoniazid against M. tuberculosis isolates that are (1) susceptible to isoniazid at 2.0 mcg/ml but resistant at 0.1 and 0.4 mcg/ml or (2) susceptible at 0.4 mcg/ml but resistant at 0.1 mcg/ml when tested in the BD MGIT 960 system. Further, the investigators will investigate the molecular genetic determinants of these differences in susceptibility.

To achieve these objectives the investigators will carry out an innovative variation on early bactericidal activity (EBA) study methodology. Patients at risk for drug-resistant TB will be screened for INH resistance using approved molecular assays. In those with INH-resistant TB, the investigators will quickly perform phenotypic DSTs using the direct method in the Bactec Mycobacterium Growth Indicator Tube (MGIT) 960 system, so results will be available within 7 days. If the DST results show the susceptibility patterns noted above, patients will receive 900 mg/d INH (600 mg if <45kg), and assess its effect with serial quantitative sputum cultures for 6 days. If the concentration of viable bacteria decreases significantly, the investigators will interpret this to mean the drug is having an effect. If not, the drug is ineffective. After 6 days, the patients will resume treatment according to national guidelines.

In case the investigators identify drugs that are effective under these conditions, the investigators will sequence known and putative genes associated with the action of these drugs for the mycobacterial isolates from these patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
    • Tamil Nadu
      • Chennai, Tamil Nadu, India
        • National Institute for Research on Tuberculosis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

8 years to 99 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Written informed consent
  • INH resistance by approved molecular genetic test
  • Phenotypic drug susceptibility test results match one of the required patterns
  • Sputum microscopy positive for acid fast bacilli

Exclusion Criteria:

  • Ineligible for MDR TB treatment according to national guidelines
  • HIV infection with CD4 count less than 50
  • Pregnancy
  • Incarceration
  • Too sick to participate (Karnofsky score <60, arterial pO2<90, respiratory rate repeatedly >25/min, clinician's judgment)
  • Hepatic enzymes >3x normal
  • Estimated glomerular filtration rate <60 mL/min/1.73 m2
  • Unable to provide adequate sputum specimen

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: High dose isoniazid
INH 900 mg daily to be administered orally for 6 days (600 mg for patients weighing <45 kg)
Drug: High dose isoniazid
See arm description
Other Names:
  • High dose INH

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Delta CFU/ml/day
Time Frame: 6 days
Change in colony forming units per ml of sputum over 6 days
6 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time-to-detection (TTD)
Time Frame: 6 days
Interval in hours from culture inoculation to detection of mycobacterial growth in MGIT 960
6 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acquired isoniazid resistance
Time Frame: 2 months
Increased level of resistance to isoniazid
2 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centers for Disease Control and Prevention

Collaborators

Kenya Medical Research Institute

Investigators

  • Principal Investigator: Sarah E. Smith-Jeffcoat, MPH, U.S. Centers for Disease Control and Prevention
  • Principal Investigator: J. P. Cegielski, MD, MPH, JP Cegielski Consulting LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2015

Primary Completion (Actual)

September 30, 2020

Study Completion (Actual)

September 30, 2020

Study Registration Dates

First Submitted

September 8, 2014

First Submitted That Met QC Criteria

September 9, 2014

First Posted (Estimate)

September 10, 2014

Study Record Updates

Last Update Posted (Actual)

October 19, 2020

Last Update Submitted That Met QC Criteria

October 13, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDC-NCHHSTP-6435

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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