Evaluation of Non-Inferiority of Two Fast Follower Nucleic Acid Amplification Tests (FIND)

Evaluation of Non-Inferiority of Two Fast Follower Nucleic Acid Amplification Tests for the Diagnosis of Pulmonary Tuberculosis in Comparison to Geneexpert MTB/RIF

Assess sensitivity and specificity of two nucleic acid amplification tests, namely Epistem Genedrive® and MolbioTruenat™ in raw sputum compared to the WHO-endorsed GeneXpert® MTB/RIF assay using a gold standard of four cultures

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: Other: Epistem Genedrive® and MolBio Truenat™

Detailed Description

• Estimate the accuracy of the Epistem Genedrive® and MolbioTruenat™ in raw sputum and in sputum pellets.
• Assess the operational feasibility of Epistem Genedrive® and MolbioTruenat™
• Determine and compare costs between the Epistem Genedrive®, MolbioTruenat™, and Xpert MTB/RIF tests

• Study Type: Observational
• Enrollment (Actual): 504

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adults with clinical suspicion of pulmonary TB.

Description

Inclusion Criteria:

• • Clinical suspicion of pulmonary TB (including cough ≥2 weeks and at least 1 other symptom typical of TB);

  • Age 18 years or above;
  • Willingness to have a study follow-up visit, if necessary, approximately two months after enrollment
  • Willingness to provide 3 sputum specimens at enrollment
  • Provision of informed consent.

Exclusion Criteria:

• • Receipt of ≥48 cumulative hours OR three or more doses of anti-TB treatment (defined as combination anti-TB therapy intended to treat active TB) within 60 days prior to completion of sputum collection;

  • Inability to provide informed consent (e.g. mentally impaired)
  • Enrolled individuals who do not provide a first sputum sample of ≥ 2ml and a second and third sputum sample of ≥ 1ml each will be classified as early exclusions.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Investigational; • Participants will be asked to provide a total of three sputum samples over Days 1 and 2. The intent is for all samples to be collected before the subject starts any form of TB treatment. The first specimen (S1) should be 2 ml or greater in volume, and the second and third specimens (S2 and S3) should each be 1 ml or greater in volume. On Day 1, each participant will be asked to submit one spot sputum (S1) after enrollment and a second spot sputum after at least 2 hours (S2). Participants will be instructed to come back the following day (Day 2) and provide a third spot sputum (S3). In the event that a participant fails to return on Day 2, S3 may be collected a maximum of 7 days after enrollment, provided that no TB treatment has been initiated.

Other: Epistem Genedrive® and MolBio Truenat™; S1 will undergo direct smear and Epistem Genedrive® (optional for phase 2*) testing, before being homogenized with glass beads and split into three portions for testing with Epistem Genedrive®, MolBio Truenat™ and GeneXpert MTB/Rif® respectively. S2 and S3 will be randomized as to the order of testing using Epistem Genedrive® and MolBio Truenat™.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-inferiority of tests	Non-inferiority of Epistem Genedrive® MTB iD Test and MolBio Truenat™ TB Assay to GeneXpert MTB/RIF using a non-inferiority margin of 5% for sensitivity in smear-positive, culture-positive; 7% for overall C+ sensitivity; and 3% for specificity in smear-negative, culture-negatives	4 months
Sensitivity and specificity of Epistem Genedrive® MTB iD	Sensitivity and specificity of Epistem Genedrive® MTB iD Test on raw sputum before homogenization, homogenized raw sputum and sputum pellet against a gold standard of concentrated smear and four cultures.	4 months
Sensitivity and specificity of MolBio Truenat™ TB Assay	Sensitivity and specificity of MolBio Truenat™ TB Assay on homogenized raw sputum and sputum pellet against a gold standard of concentrated smear and four cultures.	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Failure rate for the Epistem Genedrive® system assay and for the MolBio Truenat™ assay	Failure rate for the Epistem Genedrive® system assay and for the MolBio Truenat™ assay, expressed as the proportion of tests that require repeating due to an indeterminate or uninterpretable initial result (separately and together for tests performed on raw sputum and sputum pellet	10 months
Training needs for each assay	Training needs for each assay assessed objectively by number of hours of training, number of runs required, and successful completion of a proficiency assessment by trainees; training needs also will be assessed subjectively by the trainers and by user questionnaires	10 months
Operational feasibility	Operational feasibility will be assessed according to the infrastructure required to support each test, the robustness of the reagents and equipment (any breakdowns, storage requirements or contamination events), and the time it takes to run each test;	10 months
Cost-comparison between assays	A cost-comparison between assays assessing the cost per sample run incorporating all costs involved in transport, equipment, reagents, personnel, etc. will be performed.	10 months

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Boston Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2014
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: September 23, 2014
• First Submitted That Met QC Criteria: September 25, 2014
• First Posted (Estimate): September 30, 2014

Study Record Updates

• Last Update Posted (Actual): December 12, 2017
• Last Update Submitted That Met QC Criteria: December 8, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: NA_00085221 (Other Identifier: Johns Hopkins University)