TuberculosisPhase 4NCT01363765
Xpert MTB/Rif, a New Tool for the Diagnosis of Pulmonary Tuberculosis in Two Municipalities in Brazil
A Phase 4 study testing Xpert MTB/Rif and Smear microscopy in people with Tuberculosis, run by Ataulpho de Paiva Foundation at 1 site in Brazil.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Xpert MTB/Rif and Smear microscopy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34,758 participants
- Where
- 1 siteBrazil
- Study dates
- Feb 2012to Oct 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Laboratories of Rio de Janeiro Health Department
Rio de Janeiro, Rio de Janeiro, 22000
About this study
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
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.
Read the 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.
- Conditions
- Tuberculosis
- Being tested
- Xpert MTB/Rif, Smear microscopy
- Keywords
- diagnosis, polymerase chain reaction, sputum smear, stepped-wedge design, cost-effectiveness, Xpert MTB/Rif
- Medical subject headings
- Tuberculosis, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Xpert MTB/RifOther
Also called Intervention period
Automatized RT-PCR for the detection of Mycobacterium tuberculosis, the agent of TB, in sputum samples
Smear microscopyOther
Also called Observation
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.
| Study group | Role | What they receive |
|---|---|---|
| Xpert MTB/Rif | Experimental | Sputum specimens arriving during intervention period will be submitted to this technology, a real-time automated polymerase chain reaction test Receives: 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 Receives: Other: Smear microscopy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: October 2012 (up to 2 years)
Secondary outcomes (2)
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.
Measured: October 2012 (up to 2 years)
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.
Measured: October 2012 (up to 2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2011 (estimated)
- Study startFeb 2012
- Primary completionOct 2012
- Study completionOct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34,758 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ataulpho de Paiva Foundation
- Sponsor type
- University, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation
- Responsible party
- Sponsor
- Investigators
- Frank Cobelens, MD, PhD, Study chair, AIGHD Foundation and Department of Global Health, Academic Medical Center, University of Amsterdam
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01363765
- Sponsor's protocol ID
- OPPGH5254
- Other IDs
- GH5254
- Status last verified
- Mar 2014
- First submitted
- 27 May 2011
- Last updated
- 12 Mar 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 25915745Durovni 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.
PubMed 25490549
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01363765
- Acronym / sponsor ID
- OPPGH5254
- Conditions
- Tuberculosis
- Keywords
- diagnosis, polymerase chain reaction, sputum smear, stepped-wedge design, cost-effectiveness, Xpert MTB/Rif
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34,758 participants (actual)
- Lead sponsor
- Ataulpho de Paiva FoundationUniversity, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation
- Study start
- Feb 2012
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 2 Jun 2011 (estimated)
- Results
- Posted 12 Mar 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Xpert MTB/Rif | Experimental | Other: Xpert MTB/RifSputum specimens arriving during intervention period will be submitted to this technology, a real-time automated polymerase chain reaction test |
| Sputum smear | Active comparator | Other: Smear microscopySputum smears arriving in the laboratory during the observation period will be submitted to the classic routine smear staining |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Xpert MTB/RifAlso: Intervention periodAutomatized RT-PCR for the detection of Mycobacterium tuberculosis, the agent of TB, in sputum samples | Other | Xpert MTB/Rif |
| Smear microscopyAlso: ObservationSputum 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 | Sputum smear |
Primary outcome
Notification Rate Ratio
Time frame: 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
Time frame: 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.
2 secondary outcomes
NRR of Non-laboratory Tested TB (Cluster-averaged).
Time frame: October 2012 (up to 2 years)
NRR of Negative-laboratory TB (Cluster-averaged).
Time frame: October 2012 (up to 2 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25915745Trajman 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.
- Derived from this study: PubMed 25490549Durovni 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.
Related trials for Tuberculosis
RecruitingPhase 4
Short-term Antibiotic Therapy in Mycobacterium Avium Complex Pulmonary Disease
Mycobacterium Avium Complex Pulmonary Disease
RecruitingObservational study
Paradoxical Tuberculosis Reactions in Patients Without HIV Infection
Tuberculosis
Not yet recruitingPhase 2
Re-evaluating the Duration in Children of TB Treatment
Tuberculosis
RecruitingPhase 1/2
A Study of Daily Rifapentine Combined With Isoniazid (1HP) for Tuberculosis Prevention in Children Less Than 13 Years of Age With and Without HIV
Tuberculosis
Active, not recruitingPhase 3
Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients
Tuberculosis, MDR
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frank Cobelens, MD, PhD study chair
AIGHD Foundation and Department of Global Health, Academic Medical Center, University of Amsterdam
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Xpert MTB/Rif and Smear microscopy in people with Tuberculosis, run by Ataulpho de Paiva Foundation at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Mar 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Notification Rate Ratio (time frame: October 2012 (up to 2 years)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01363765, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2014.