GCDD: Global Consortium for Drug-resistant Tuberculosis Diagnostics

Sponsor

University of California, San Diego (Other)

Overall Status

Completed

CT.gov ID

NCT02170441

Collaborator

National Institutes of Health (NIH) (NIH), National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

1,128

Enrollment

Locations

Duration (Months)

376

Patients Per Site

14.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this study is to evaluate time to diagnosis for three assays (line probe, pyrosequencing, and Microscopic Observation Drug Susceptibility Assay [MODS]) to detect resistance to first and second-line anti-tuberculosis (TB) drugs in Mycobacterium tuberculosis (Mtb) strains in 7 days or less, allowing for rapid diagnosis of extensively drug-resistant TB (XDR-TB).

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis Tuberculosis, Multidrug-Resistant

Detailed Description

The goals of this study are to test, fine tune, and compare three tests (line probe, pyrosequencing, MODS assays) to rapidly detect Mycobacterium tuberculosis (Mtb) strains that are resistant to first and second-line anti-tuberculosis (TB) drugs allowing for rapid diagnosis of Extensively Drug-Resistant Tuberculosis (XDR-TB).

Primary Specific Aims

Aim 1: To reduce the average XDR-TB detection time from months to a week.

Aim 2: To determine agreement between rapid tests and standard drug susceptibility testing (DST) results.

Aim 3: To identify the genetic basis of discordant results from Aim 2.

Aim 4: To characterize genotypic, phenotypic and epidemiological features, as well as geographical relationships, of XDR-TB strains compared to other drug-resistant and susceptible strains.

Secondary Aims Aim 1: Cost-effectiveness study. The costs associated with rapid-test implementation will be compared with the performance of the new tests to rapidly and accurately detect drug resistance and XDR-TB.

Aim 2: To determine the predictive value of resistance-associated mutations in determining sputum culture conversion.

The investigators hypothesize that analysis of the genotypic basis of anti-TB drug resistance will allow for the development of improved rapid molecular drug susceptibility tests that will detect resistance to fluoroquinolones and injectable anti-TB drugs and reduce the current XDR-TB diagnosis time of up to three months to less than seven days.

Study Design

Study Type:

Observational

Actual Enrollment :

1128 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Global Consortium for Drug-resistant Tuberculosis Diagnostics

Study Start Date :

Apr 1, 2012

Actual Primary Completion Date :

Jun 1, 2014

Actual Study Completion Date :

Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Patients at risk for drug-resistant TB No intervention

Outcome Measures

Primary Outcome Measures

Time to completion of rapid diagnostic assays [Up to 83 weeks]
Time to completion was calculated from date of initial sputum collection to completion of each rapid diagnostic assay. Time frame for analysis of all results was from date of first patient recruited till 21 weeks after last patient recruited (total 83 weeks).

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

At least 5 years of age
Known to be acid fast bacilli (AFB) sputum smear-positive, 1+ or greater (within prior 14 days), positive on GeneXpert, or present clinically with high suspicion of active

TB and:

Had previously received >1 month of treatment for a prior TB episode or
Were failing TB treatment with positive sputum smear or culture after ≥3 months of a standard TB treatment or
Had had close contact with a known drug-resistant TB case or
Were newly diagnosed with multi-drug resistant TB (MDR-TB) within the last 30 days or
Were previously diagnosed with MDR-TB and failed TB treatment with positive sputum smear or culture after ≥3 months of a standard MDR-TB treatment regimen
Provided informed consent or had ability and willingness of subject or legal guardian/representative to provide informed consent

Exclusion Criteria:

Institutionalized
Unable to provide at least 7.5ml sputum (1st and 2nd samples combined)
Had results from second line DST performed within the last 3 months

Contacts and Locations

Locations

	Site	City	Country
1	P.D. Hinduja National Hospital and Medical Research Centre	Mumbai	India
2	Phthisiopneumology Institute	Chisinau	Moldova, Republic of
3	Department of Biomedical Sciences, Stellenbosch University	Cape Town	South Africa