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Brief Bactericidal Activity of Anti-Tuberculosis Drugs

NCT02236078 · Status: COMPLETED · Phase: PHASE1 · Type: INTERVENTIONAL · Enrollment: 18

Last updated 2020-10-19

No results posted yet for this study

Summary

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.

Conditions

  • Tuberculosis
  • Drug-resistant Tuberculosis
  • Isoniazid Resistant Tuberculosis (Disorder)

Interventions

DRUG

High dose isoniazid

See arm description

Sponsors & Collaborators

Principal Investigators

  • Sarah E. Smith-Jeffcoat, MPH · U.S. Centers for Disease Control and Prevention

  • J. P. Cegielski, MD, MPH · JP Cegielski Consulting LLC

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
8 Years
Max Age
99 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2015-11-30
Primary Completion
2020-09-30
Completion
2020-09-30

Countries

  • India

Study Locations

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Entities

Diseases
Companies

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02236078 on ClinicalTrials.gov