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

Phase 4

Completed

Conditions: Tuberculosis

Interventions: Other: Xpert MTB/Rif
Other: Smear microscopy

Registration Number: NCT01363765

Lead Sponsor: Ataulpho de Paiva Foundation

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 34758

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.

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Xpert MTB/Rif	Xpert MTB/Rif	Sputum specimens arriving during intervention period will be submitted to this technology, a real-time automated polymerase chain reaction test
Sputum smear	Smear microscopy	Sputum smears arriving in the laboratory during the observation period will be submitted to the classic routine smear staining

Primary Outcome Measures

Name	Time	Method
Notification Rate Ratio	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.
Costs Per Detected Case	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.

Secondary Outcome Measures

Name	Time	Method
NRR of Non-laboratory Tested TB (Cluster-averaged).	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.
NRR of Negative-laboratory TB (Cluster-averaged).	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.