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

This study has been completed.
Sponsor:
Collaborator:
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
Ataulpho de Paiva Foundation
ClinicalTrials.gov Identifier:
NCT01363765
First received: May 27, 2011
Last updated: March 11, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Tuberculosis
Other: Xpert MTB/Rif
Other: Smear microscopy
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Ataulpho de Paiva Foundation:

Primary Outcome Measures:
  • Notification Rate Ratio [ Time Frame: October 2012 (up to 2 years) ] [ Designated as safety issue: No ]
    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 [ Time Frame: October 2012 (up to 2 years) ] [ Designated as safety issue: No ]
    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:
  • NRR of Non-laboratory Tested TB (Cluster-averaged). [ Time Frame: October 2012 (up to 2 years) ] [ Designated as safety issue: No ]

    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). [ Time Frame: October 2012 (up to 2 years) ] [ Designated as safety issue: No ]

    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.



Enrollment: 34758
Study Start Date: February 2012
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Observation

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

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01363765

Locations
Brazil
Laboratories of Rio de Janeiro Health Department
Rio de Janeiro, RJ, Brazil, 22000
Sponsors and Collaborators
Ataulpho de Paiva Foundation
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
  More Information

Additional Information:
No publications provided

Responsible Party: Ataulpho de Paiva Foundation
ClinicalTrials.gov Identifier: NCT01363765     History of Changes
Other Study ID Numbers: OPPGH5254, GH5254
Study First Received: May 27, 2011
Results First Received: August 5, 2013
Last Updated: March 11, 2014
Health Authority: Brazil: National Health Surveillance Agency

Keywords provided by Ataulpho de Paiva Foundation:
diagnosis
polymerase chain reaction
sputum smear
stepped-wedge design
cost-effectiveness
Xpert MTB/Rif

Additional relevant MeSH terms:
Tuberculosis
Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections

ClinicalTrials.gov processed this record on September 11, 2014