Xpert MTB/Rif, a New Tool for the Diagnosis of Pulmonary Tuberculosis in Two Municipalities in Brazil

March 11, 2014 updated by: Ataulpho de Paiva Foundation

Pilot Roll Out of the Xpert MTB/Rif for the Diagnosis of Pulmonary Tuberculosis in Two Municipalities in Brazil: a Stepped Wedge Trial

Diagnosis of tuberculosis (TB) is a challenge because sputum smear, the most rapid and inexpensive test, often fails to detect the disease, in around 20 to 30% of cases. Culture of sputum yields a correct diagnosis in up to 90% of cases, but results are only available in 4 to 8 weeks, depending on the method. A new test (Xpert MTB/Rif) based on a rapid technique, named polymerase chain reaction (PCR), detects TB in less than 2 hours over 95% of cases, in addition to identification of cases resistant to certain drugs used to treat TB. The test is expensive, but several studies have demonstrated its accuracy, and since most steps are automatized, savings can be expected from human resources work. The aims of our study are (1) to evaluate this tool as a substitute test for sputum smears in routine conditions; (2) evaluate if it is cost-effective, meaning that effectiveness of the test may outweigh the extra cost, and (3) evaluate the acceptability of the test among patients and health care workers.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The main study consisted of a group-randomized pragmatic trial following a stepped-wedge design. The GeneXpert machines will be installed in laboratories of the basic health units in Rio de Janeiro and Manaus, two cities with a high burden of the disease in Brazil. Doctors will prescribe routine tests in the clinics. When sputum specimens arrive in the laboratory, instead of performing smears, the Xpert MTB/Rif will be performed during the intervention period. If positive, a sputum smear will also be performed. The intervention period will be preceded by an observation period during which routine will be kept unchanged, i.e., only smears will be performed. The observation period will serve as a comparator (control). The investigators will then see how many more cases were detected during the intervention period, and in particular, how many smear-negative cases were detected, compared to the observation period.

A total of 35,000 specimens are expected to be tested with the new technology in 14 laboratories. Laboratories, not individuals, will be randomized.

Study Type

Interventional

Enrollment (Actual)

34758

Phase

  • Phase 4

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

  • Brazil
    • RJ
      • Rio de Janeiro, RJ, Brazil, 22000
        • Laboratories of Rio de Janeiro Health Department

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

laboratories -and not subjects - will be randomized. All laboratories will start doing smears, when indicated by randomization, they will switch to Xpert MTB/Rif. There are no inclusion or exclusion criteria for the labs. Sputum specimens from non-diagnostic (follow up) patients, second samples for diagnostic tests, insufficient volume/visible blood specimens will be excluded from the Xpert testing.

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: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Xpert MTB/Rif
Sputum specimens arriving during intervention period will be submitted to this technology, a real-time automated polymerase chain reaction test
Other: Xpert MTB/Rif
Automatized RT-PCR for the detection of Mycobacterium tuberculosis, the agent of TB, in sputum samples
Other Names:
  • Intervention period
Active Comparator: Sputum smear
Sputum smears arriving in the laboratory during the observation period will be submitted to the classic routine smear staining
Other: Smear microscopy
Sputum smears arriving in the laboratory during the observation period will be submitted to the classic routine smear staining. This would be the non-intervention (control) arm.
Other Names:
  • Observation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Notification Rate Ratio
Time Frame: October 2012 (up to 2 years)
Proportion of additional bacteriologically confirmed notified TB cases during intervention period compared to the observation period Patients notified who had a positive test result. The notification rate (NR, i.e., number of notifications/100,000 population/year) ratio (NRR) is defined as the NR in the intervention period/NR in the observation period, and is presented in the statistical analysis section.
October 2012 (up to 2 years)
Costs Per Detected Case
Time Frame: October 2012 (up to 2 years)
Costs per detected case were analyzed using a decision tree model from the national health system perspective. Incremental cost-effectiveness ratio (ICER) was calculated as (costs with Xpert - costs with smears)/(cases detected with Xpert - cases detected with smears). Negative ICERs mean cost saving.
October 2012 (up to 2 years)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
NRR of Non-laboratory Tested TB (Cluster-averaged).
Time Frame: October 2012 (up to 2 years)

The notification rate (NR, i.e., number of notifications/100,000 population/year) ratio (NRR) is defined as the NR in the intervention period/NR in the observation period, and is presented in the statistical analysis section.

Numbers are participants in the notification database who were not in the lab (all tests done) database; denominators are population taking into account growth of the population during the study period, adjusted for variations in monthly number of opening days (by weighing the number of person-months for the proportion of suspects with samples examined each month out of the total number examined by the laboratory during the whole study period), stratified by sex and age group.

Routine practices were not changed; patients with a high suspicion of TB were, as prior to the study, notified regardless of a confirmatory test.
October 2012 (up to 2 years)
NRR of Negative-laboratory TB (Cluster-averaged).
Time Frame: October 2012 (up to 2 years)

The notification rate (NR, i.e., number of notifications/100,000 population/year) ratio (NRR) is defined as the NR in the intervention period/NR in the observation period, and is presented in the statistical analysis section.

Numbers are driven from linkage between lab (all tests done) and notification databases; denominators are population taking into account growth of the population during the study period, adjusted for variations in monthly number of opening days (by weighing the number of person-months for the proportion of suspects with samples examined each month out of the total number examined by the laboratory during the whole study period), stratified by sex and age group.

Routine practices were not changed; patients with a high suspicion of TB were, as prior to the study, notified regardless of a confirmatory test.
October 2012 (up to 2 years)

Collaborators and Investigators

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

Sponsor

Ataulpho de Paiva Foundation

Collaborators

Bill and Melinda Gates Foundation

Investigators

  • Study Chair: Frank Cobelens, MD, PhD, AIGHD Foundation and Department of Global Health, Academic Medical Center, University of Amsterdam

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

February 1, 2012

Primary Completion (Actual)

October 1, 2012

Study Completion (Actual)

October 1, 2012

Study Registration Dates

First Submitted

May 27, 2011

First Submitted That Met QC Criteria

June 1, 2011

First Posted (Estimate)

June 2, 2011

Study Record Updates

Last Update Posted (Estimate)

March 12, 2014

Last Update Submitted That Met QC Criteria

March 11, 2014

Last Verified

March 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OPPGH5254
  • GH5254 (Other Grant/Funding Number: Bill and Melinda Gates Foundation)

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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