Global Consortium for Drug-resistant Tuberculosis Diagnostics

NCT ID: NCT02170441

Last Updated: 2014-06-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

1128 participants

Study Classification

OBSERVATIONAL

Study Start Date

2012-04-30

Study Completion Date

2014-06-30

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Tuberculosis Tuberculosis, Multidrug-Resistant

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Patients at risk for drug-resistant TB

No intervention

No interventions assigned to this group

Eligibility Criteria

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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
Minimum Eligible Age

5 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

University of California, San Diego

OTHER

Sponsor Role lead

Responsible Party

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Antonino Catanzaro

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Antonino Catanzaro, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Locations

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P.D. Hinduja National Hospital and Medical Research Centre

Mumbai, , India

Site Status

Phthisiopneumology Institute

Chisinau, , Moldova

Site Status

Department of Biomedical Sciences, Stellenbosch University

Cape Town, , South Africa

Site Status

Countries

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India Moldova South Africa

References

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Groessl EJ, Ganiats TG, Hillery N, Trollip A, Jackson RL, Catanzaro DG, Rodwell TC, Garfein RS, Rodrigues C, Crudu V, Victor TC, Catanzaro A. Cost analysis of rapid diagnostics for drug-resistant tuberculosis. BMC Infect Dis. 2018 Mar 2;18(1):102. doi: 10.1186/s12879-018-3013-0.

Reference Type DERIVED
PMID: 29499645 (View on PubMed)

Seifert M, Georghiou SB, Garfein RS, Catanzaro D, Rodwell TC. Impact of Fluoroquinolone Use on Mortality Among a Cohort of Patients With Suspected Drug-Resistant Tuberculosis. Clin Infect Dis. 2017 Sep 1;65(5):772-778. doi: 10.1093/cid/cix422.

Reference Type DERIVED
PMID: 28475735 (View on PubMed)

Georghiou SB, Seifert M, Catanzaro DG, Garfein RS, Rodwell TC. Increased Tuberculosis Patient Mortality Associated with Mycobacterium tuberculosis Mutations Conferring Resistance to Second-Line Antituberculous Drugs. J Clin Microbiol. 2017 Jun;55(6):1928-1937. doi: 10.1128/JCM.00152-17. Epub 2017 Apr 12.

Reference Type DERIVED
PMID: 28404672 (View on PubMed)

Catanzaro DG, Trollip AP, Seifert M, Georghiou SB, Garfein RS, Rodwell TC, Catanzaro A, Eisenach KD. Evaluation of the microscopic observation drug susceptibility assay for the detection of first- and second-line drug susceptibility for Mycobacterium tuberculosis. Eur Respir J. 2017 Apr 5;49(4):1602215. doi: 10.1183/13993003.02215-2016. Print 2017 Apr.

Reference Type DERIVED
PMID: 28381434 (View on PubMed)

Georghiou SB, Seifert M, Lin SY, Catanzaro D, Garfein RS, Jackson RL, Crudu V, Rodrigues C, Victor TC, Catanzaro A, Rodwell TC. Shedding light on the performance of a pyrosequencing assay for drug-resistant tuberculosis diagnosis. BMC Infect Dis. 2016 Aug 31;16(1):458. doi: 10.1186/s12879-016-1781-y.

Reference Type DERIVED
PMID: 27576542 (View on PubMed)

Georghiou SB, Seifert M, Catanzaro D, Garfein RS, Valafar F, Crudu V, Rodrigues C, Victor TC, Catanzaro A, Rodwell TC. Frequency and Distribution of Tuberculosis Resistance-Associated Mutations between Mumbai, Moldova, and Eastern Cape. Antimicrob Agents Chemother. 2016 Jun 20;60(7):3994-4004. doi: 10.1128/AAC.00222-16. Print 2016 Jul.

Reference Type DERIVED
PMID: 27090176 (View on PubMed)

Hillery N, Groessl EJ, Trollip A, Catanzaro D, Jackson L, Rodwell TC, Garfein RS, Lin SY, Eisenach K, Ganiats TG, Park D, Valafar F, Rodrigues C, Crudu V, Victor TC, Catanzaro A. The Global Consortium for Drug-resistant Tuberculosis Diagnostics (GCDD): design of a multi-site, head-to-head study of three rapid tests to detect extensively drug-resistant tuberculosis. Trials. 2014 Nov 6;15:434. doi: 10.1186/1745-6215-15-434.

Reference Type DERIVED
PMID: 25377177 (View on PubMed)

Related Links

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Other Identifiers

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U01AI082229

Identifier Type: NIH

Identifier Source: secondary_id

View Link

09-0099

Identifier Type: -

Identifier Source: org_study_id

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