Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| GH5254 | Other Grant/Funding Number | Bill and Melinda Gates Foundation |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Bill and Melinda Gates Foundation | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Xpert MTB/Rif | Experimental | Sputum specimens arriving during intervention period will be submitted to this technology, a real-time automated polymerase chain reaction test |
|
| Sputum smear | Active Comparator | Sputum smears arriving in the laboratory during the observation period will be submitted to the classic routine smear staining |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Xpert MTB/Rif | Other | Automatized RT-PCR for the detection of Mycobacterium tuberculosis, the agent of TB, in sputum samples |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Frank Cobelens, MD, PhD | AIGHD Foundation and Department of Global Health, Academic Medical Center, University of Amsterdam | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Laboratories of Rio de Janeiro Health Department | Rio de Janeiro | Rio de Janeiro | 22000 | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25915745 | Derived | 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. | |
| 25490549 |
Not provided
Not provided
Samples (and not patients) were included if it was a first diagnostic sample in the intervention arm. Follow up (non diagnostic) samples were excluded for both arms, as were inadequate samples (insufficient material, blood stained-specimens) in the intervention group.
From Feb 4 to Oct 4 2012, all 11 primary care laboratories in Rio de Janeiro and 3 labs covering 70% of PTB diagnosis in Manaus participated. Over the same period, 4,660 patients were notified with PTB to SINAN (disease information database). Of these, 2,745 (59%) could be linked to test results in GAL (lab information system).
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Xpert MTB/Rif | Sputum specimens arriving during intervention period were submitted to this technology, a real-time automated polymerase chain reaction test |
| FG001 | Sputum Smear | Sputum smears arriving in the laboratory during the observation period were submitted to the classic routine AFB smear staining, as per national guidelines. Two smears were requested. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Those are notified patients with pulmonary TB by the clinics which drain to the 14 participant labs all participants who were notified whether or not they were linked to the lab database. Further analyses do not correspond to all notified patients, it included only those linked in both databases.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Xpert MTB/Rif | One sample of sputum specimens arriving during intervention period were submitted to this technology instead, a real-time automated polymerase chain reaction test |
| BG001 | Sputum Smear |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Only patients found both in laboratory and in the notification databases were included since this is an outcome based on notification rates. Population growth during time was estimated. NR per 100,000 population | Posted | Number | 95% Confidence Interval | notifications/100,000 persons/year | October 2012 (up to 2 years) |
|
Not provided
Serious and Other (non-serious) Adverse Events were not collected/assessed
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Xpert MTB/Rif | Sputum specimens arriving during intervention period were submitted to this technology, a real-time automated polymerase chain reaction test |
Not provided
Not provided
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Anete Trajman | InCo-TB project, Gama Filho University | 5521-82189194 | atrajman@gmail.com |
Not provided
| ID | Term |
|---|---|
| D014376 | Tuberculosis |
| D004194 | Disease |
| ID | Term |
|---|---|
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| D019370 | Observation |
| ID | Term |
|---|---|
| D008722 | Methods |
| D008919 | Investigative Techniques |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| 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. |
|
|
| 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. | October 2012 (up to 2 years) |
| 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. |
| non-resident |
|
| age not recorded (used for cross-linkage |
|
| smear during intervention |
|
Sputum smears arriving in the laboratory during the observation period will be submitted to the classic routine smear staining
| BG002 | Total | Total of all reporting groups |
| participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Sputum Smear | Sputum smears arriving in the laboratory during the observation period were submitted to the classic routine smear staining |
|
|
|
| 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. | Posted | Number | American dollars | October 2012 (up to 2 years) |
|
|
|
|
| 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. | The result is the notification rate ratio | Posted | Number | 95% Confidence Interval | notifications/100,000 persons/year | October 2012 (up to 2 years) |
|
|
|
|
| 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. | Posted | Number | 95% Confidence Interval | notifications/100,000 persons/year | October 2012 (up to 2 years) |
|
|
|
|
| 0 |
| 0 |
| 0 |
| 0 |
| EG001 | Sputum Smear | Sputum smears arriving in the laboratory during the observation period were submitted to the classic routine AFB smear staining, as per national guidelines. Two smears were requested. | 0 | 0 | 0 | 0 |
Not provided
Not provided
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |