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

NCT01363765 | Completed Phase 4 Results

• 2 other identifiers: OPPGH5254GH5254
• Study Type: interventional
• Target: 34,758
• Locations: 1 country
• Sites: 1

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.

Conditions

Tuberculosis

Keywords

diagnosis; polymerase chain reaction; sputum smear; stepped-wedge design; cost-effectiveness; Xpert MTB/Rif

Outcome Measures

Primary Outcomes (2)

• 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)

• 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)

Secondary Outcomes (2)

• NRR of Non-laboratory Tested TB (Cluster-averaged).

  October 2012 (up to 2 years)

• NRR of Negative-laboratory TB (Cluster-averaged).

  October 2012 (up to 2 years)

Study Arms (2)

Xpert MTB/Rif

EXPERIMENTAL

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

Other: Xpert MTB/Rif

Sputum smear

ACTIVE COMPARATOR

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

Other: Smear microscopy

Interventions

Xpert MTB/Rif OTHER

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

Also known as: Intervention period

Xpert MTB/Rif

Smear microscopy 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.

Also known as: Observation

Sputum smear

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

Sponsors & Collaborators

• Ataulpho de Paiva Foundation: lead
• Bill and Melinda Gates Foundation: collaborator

Study Sites (1)

Laboratories of Rio de Janeiro Health Department

Rio de Janeiro, Rio de Janeiro, 22000, Brazil

Location

Related Publications (2)

• 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.

  PMID: 25915745 DERIVED

• 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.

  PMID: 25490549 DERIVED

MeSH Terms

Conditions

Tuberculosis; Disease

Interventions

Observation

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Limitations and Caveats

The design has potential for bias, due to delayed treatment effects or to conditions that change over time. Both are unlikely: outcome (notification) was shortly after test and adjustment for time in multilevel mixed model confirmed primary analysis.

Results Point of Contact

• Title: Anete Trajman
• Organization: InCo-TB project, Gama Filho University

atrajman@gmail.com

5521-82189194

Study Officials

• Frank Cobelens, MD, PhD

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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2011
• First Posted: June 2, 2011
• Study Start: February 1, 2012
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: March 12, 2014
• Results First Posted: March 12, 2014

Record last verified: 2014-03

Locations

BR (1)