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

Tuberculosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01363765
• Other study ID #: OPPGH5254
• Secondary ID: GH5254
• Status: Completed
• Phase: Phase 4
• First received: May 27, 2011
• Last updated: March 11, 2014
• Start date: February 2012
• Est. completion date: October 2012

Study information

• Verified date: March 2014
• Source: Ataulpho de Paiva Foundation
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Health Surveillance Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34758
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Tuberculosis
• Tuberculosis, Pulmonary

Intervention

Other:
• Xpert MTB/Rif
Automatized RT-PCR for the detection of Mycobacterium tuberculosis, the agent of TB, in sputum samples
• 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.

Locations

Country	Name	City	State
Brazil	Laboratories of Rio de Janeiro Health Department	Rio de Janeiro	RJ

Sponsors (2)

Lead Sponsor	Collaborator
Ataulpho de Paiva Foundation	Bill and Melinda Gates Foundation

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Notification Rate Ratio	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)	No
Primary	Costs Per Detected Case	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)	No
Secondary	NRR of Non-laboratory Tested TB (Cluster-averaged).	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)	No
Secondary	NRR of Negative-laboratory TB (Cluster-averaged).	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)	No