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

NCT ID: NCT01363765

Last Updated: 2014-03-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 34758 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2012-10-31

Brief Summary

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.

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.

Conditions

Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Xpert MTB/Rif

Sputum specimens arriving during intervention period will be submitted to this technology, a real-time automated polymerase chain reaction test

Group Type: EXPERIMENTAL

Xpert MTB/Rif

Intervention Type: OTHER

Automatized RT-PCR for the detection of Mycobacterium tuberculosis, the agent of TB, in sputum samples

Sputum smear

Sputum smears arriving in the laboratory during the observation period will be submitted to the classic routine smear staining

Group Type: ACTIVE_COMPARATOR

Smear microscopy

Intervention Type: OTHER

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.

Interventions

Xpert MTB/Rif

Automatized RT-PCR for the detection of Mycobacterium tuberculosis, the agent of TB, in sputum samples

Intervention Type: 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.

Intervention Type: OTHER

Other Intervention Names

Intervention period; Observation

Eligibility Criteria

Inclusion Criteria

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.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bill and Melinda Gates Foundation

OTHER

Sponsor Role: collaborator

Ataulpho de Paiva Foundation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Frank Cobelens, MD, PhD

Role: STUDY_CHAIR

AIGHD Foundation and Department of Global Health, Academic Medical Center, University of Amsterdam

Locations

Laboratories of Rio de Janeiro Health Department

Rio de Janeiro, Rio de Janeiro, Brazil

Countries

Brazil

References

Trajman A, Durovni B, Saraceni V, Menezes A, Cordeiro-Santos M, Cobelens F, Van den Hof S. Impact on Patients' Treatment Outcomes of XpertMTB/RIF Implementation for the Diagnosis of Tuberculosis: Follow-Up of a Stepped-Wedge Randomized Clinical Trial. PLoS One. 2015 Apr 27;10(4):e0123252. doi: 10.1371/journal.pone.0123252. eCollection 2015.

Reference Type: DERIVED

PMID: 25915745 (View on PubMed)

Durovni B, Saraceni V, van den Hof S, Trajman A, Cordeiro-Santos M, Cavalcante S, Menezes A, Cobelens F. Impact of replacing smear microscopy with Xpert MTB/RIF for diagnosing tuberculosis in Brazil: a stepped-wedge cluster-randomized trial. PLoS Med. 2014 Dec 9;11(12):e1001766. doi: 10.1371/journal.pmed.1001766. eCollection 2014 Dec.

Reference Type: DERIVED

PMID: 25490549 (View on PubMed)

Other Identifiers

GH5254

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

OPPGH5254

Identifier Type: -

Identifier Source: org_study_id