Clinical trial NCT01363765: Xpert MTB/Rif, a New Tool for the Diagnosis of Pulmonary Tuberculosis in Two Municipalities in Brazil
Official title: Pilot Roll Out of the Xpert MTB/Rif for the Diagnosis of Pulmonary Tuberculosis in Two Municipalities in Brazil: a Stepped Wedge Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Tuberculosis
Keywords: diagnosis
polymerase chain reaction
sputum smear
stepped-wedge design
cost-effectiveness
Xpert MTB/Rif
Lead sponsor: Ataulpho de Paiva Foundation
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
First posted: 2011-06-02
Enrollment: 34758
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

Eligibility 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.

Primary outcomes:
measure: Notification Rate Ratio
timeFrame: October 2012 (up to 2 years)
measure: Costs Per Detected Case
timeFrame: October 2012 (up to 2 years)
Secondary outcomes:
measure: NRR of Non-laboratory Tested TB (Cluster-averaged).
timeFrame: October 2012 (up to 2 years)
measure: NRR of Negative-laboratory TB (Cluster-averaged).
timeFrame: October 2012 (up to 2 years)
Other outcomes:
Locations:
city: Rio de Janeiro
country: Brazil
facility: Laboratories of Rio de Janeiro Health Department
state: RJ
Study officials:
affiliation: AIGHD Foundation and Department of Global Health, Academic Medical Center, University of Amsterdam
name: Frank Cobelens, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.