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| ID | Type | Description | Link |
|---|---|---|---|
| R21AI161301 | U.S. NIH Grant/Contract | View source | |
| IRB00015699 | Other Identifier | JHSPH IRB |
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| Name | Class |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
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Although curative treatment exists, tuberculosis (TB) remains the leading cause of infectious mortality worldwide - often because people seek care for TB symptoms in highly resource-constrained clinics that cannot provide same-day diagnostic testing. The research team has developed an easy-to-use clinical risk score that, if implemented in these settings, might help clinicians identify patients at high risk for TB and thereby start treatment for those patients on the same day. This study will investigate the effectiveness and implementation of this score in four peri-urban clinics in Uganda, providing critical pragmatic data to inform (or halt) the design of a definitive large-scale cluster randomized trial.
An estimated 1.5 million people die of tuberculosis (TB) every year. Many of these are people who seek care in under-resourced clinics (for example, in rural areas or informal settlements) where same-day TB diagnosis is not available. These patients are often unable to return promptly to receive their results and start treatment, resulting in ongoing disease transmission and often death. If TB treatment could be started on the same day as these patients initially seek care, substantial mortality and transmission could be averted. The research team has developed and validated a clinical risk score ("PredicTB") for adult pulmonary TB that could aid in clinical decision-making. This risk score ranges from 1-10, can be calculated by hand in under a minute using readily available clinical data (e.g., age, sex, self-reported HIV status), and has sufficiently high accuracy to inform decisions about same-day empiric treatment initiation while confirmatory test results are pending. Same-day treatment initiation improves patient outcomes for other infectious diseases (for example, sexually transmitted diseases including HIV), and this novel clinical risk score holds similar promise for TB, the leading cause of infectious mortality worldwide. However, before conducting a large-scale cluster randomized trial to evaluate whether this score could improve patient-important outcomes, it is critical to first generate evidence that this score could be effective and be implemented in the most-resource-limited settings for which it is intended.
The research team proposes a type 2 hybrid effectiveness-implementation evaluation of the PredicTB clinical risk score in four peri-urban clinics in Uganda, with an additional four clinics serving as a comparison group. The Specific Aims are to evaluate the effectiveness of PredicTB on clinical outcomes including rapid treatment initiation, TB mortality, and loss to care (Aim 1); to evaluate the implementation of PredicTB in terms of reach, adoption, implementation, and maintenance (Aim 2); and the project the long-term impact and cost-effectiveness of PredicTB implementation (Aim 3). The primary outcome is the increase in the proportion of patients with microbiologically confirmed TB who start treatment within seven days of initial presentation. To accomplish these aims, the research team will adopt a highly pragmatic study design in which the research team train clinicians in the use of the PredicTB score and perform quarterly site visits but otherwise minimize contact between study staff and treating clinicians. This will enable the research team to evaluate whether implementation of PredicTB is likely to impact clinical decision-making and patient outcomes under actual field settings. If successful, this evaluation will provide critical data to justify (or halt) the conduct of a large-scale pragmatic clinical trial - not only will it generate preliminary evidence of effectiveness, but it will also inform appropriate implementation. Patients in highly resource-constrained settings are at the greatest risk of suffering the ill effects of TB disease, including long-term morbidity and death. This study represents an important first step toward improving clinical management for these marginalized patients and thus toward reaching global targets for ending the TB epidemic.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Score intervention arm | Experimental | The PredicTB score will be implemented in this arm. |
|
| Control arm | No Intervention | The standard of care will be conducted in this arm. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PredicTB score | Other | This is an easy-to-use clinical risk score designed to improve early management of tuberculosis in highly resource-constrained settings where same-day microbiological testing is unavailable. It consists of readily accessible demographic and clinical data and is scored from 1-10. We will train clinic staff in eight clinics (four study clinics and four comparison clinics) on the Ugandan standard of care for the diagnosis and treatment of TB. In addition, in the four study clinics, we will provide training on the PredicTB score. |
| Measure | Description | Time Frame |
|---|---|---|
| Difference in 7-day Treatment Initiation From Pre-implementation to Post-implementation | The percentage of participants with microbiologically confirmed TB who initiated treatment within 7 days during post-implementation 'minus' The percentage of participants with microbiologically confirmed TB who initiated treatment within 7 days during pre-implementation | Up to 12 months post intervention |
| Implementation: Percentage of Encountered Patients at Intervention Arm Who Initiated the Same-day Treatment Based on PredicTB Score as Indicated | Percentage of patients who initiated same-day treatment divided by the number of patients who had a higher PredicTB score than the clinic-specific score of treatment threshold in the post-implementation period in intervention arm | Up to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Incremental Cost-effectiveness of PredicTB | (cost of implementing PredicTB - cost of standard of care)/(projected disability-adjusted life years (DALYs) in standard of care - projected DALYs with PredicTB) | Months 0 - 12 |
| Difference in TB Mortality From Pre-implementation to Post-implementation |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David W Dowdy, MD/PHD | Johns Hopkins Bloomberg School of Public Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Makerere University | Kampala | Uganda |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40587503 | Derived | Baik Y, Musoke M, Twinamasiko A, Lamunu M, Nabacwa V, Sanyu A, Robsky KO, Sung J, Kityamuwesi A, Katamba A, Dowdy DW. Effectiveness and Implementation of a Clinical Risk Score for Early Diagnosis of Tuberculosis in Uganda: A Pragmatic, Clustered Randomization Clinical Trial. Ann Am Thorac Soc. 2025 Oct;22(10):1476-1483. doi: 10.1513/AnnalsATS.202404-422OC. |
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The study was initially conducted in eight primary health clinics (four clinics in the intervention arm and the other four clinics in the control arm). During the study, a total of three clinics (two in the intervention arm and one in the control arm) were replaced with other facilities of similar size and location for the remainder of the study period, resulting in 11 participating clinics.
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| ID | Title | Description |
|---|---|---|
| FG000 | Score Intervention Arm | The PredicTB score will be implemented in this arm. PredicTB score: This is an easy-to-use clinical risk score designed to improve early management of tuberculosis in highly resource-constrained settings where same-day microbiological testing is unavailable. It consists of readily accessible demographic and clinical data and is scored from 1-10. We will train clinic staff in eight clinics (four study clinics and four comparison clinics) on the Ugandan standard of care for the diagnosis and treatment of TB. In addition, in the four study clinics, we will provide training on the PredicTB score. |
| FG001 | Control Arm | The standard of care will be conducted in this arm. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Score Intervention Arm | The PredicTB score will be implemented in this arm. PredicTB score: This is an easy-to-use clinical risk score designed to improve early management of tuberculosis in highly resource-constrained settings where same-day microbiological testing is unavailable. It consists of readily accessible demographic and clinical data and is scored from 1-10. We will train clinic staff in eight clinics (four study clinics and four comparison clinics) on the Ugandan standard of care for the diagnosis and treatment of TB. In addition, in the four study clinics, we will provide training on the PredicTB score. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | Difference in 7-day Treatment Initiation From Pre-implementation to Post-implementation | The percentage of participants with microbiologically confirmed TB who initiated treatment within 7 days during post-implementation 'minus' The percentage of participants with microbiologically confirmed TB who initiated treatment within 7 days during pre-implementation | This outcome includes individuals who were diagnosed with tuberculosis. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 12 months post intervention |
|
An average of 281 days
Per Study Protocol, all-cause mortality and (serious and other than serious) adverse events were collected only from individuals who were diagnosed with tuberculosis during the post-implementation phase. Therefore, the number at risk is different from the number of participants with tuberculosis symptom presentation (the starting number of participants of the study).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Score Intervention Arm | The PredicTB score will be implemented in this arm. PredicTB score: This is an easy-to-use clinical risk score designed to improve early management of tuberculosis in highly resource-constrained settings where same-day microbiological testing is unavailable. It consists of readily accessible demographic and clinical data and is scored from 1-10. We will train clinic staff in eight clinics (four study clinics and four comparison clinics) on the Ugandan standard of care for the diagnosis and treatment of TB. In addition, in the four study clinics, we will provide training on the PredicTB score. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Yeonsoo Baik | Johns Hopkins Bloomberg School of Public Health | 410-955-2378 | ybaik3@jh.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 3, 2021 | May 24, 2024 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | May 21, 2021 | May 24, 2024 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D014397 | Tuberculosis, Pulmonary |
| ID | Term |
|---|---|
| D014376 | Tuberculosis |
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
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The study includes an intervention arm (four clinics) and a control arm (four clinics).
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The percentage of participants with microbiologically confirmed TB who died of any cause in the post-implementation "minus" The percentage of participants with microbiologically confirmed TB who died of any cause in the pre-implementation |
| 12 Months |
| Difference in Loss to Care From Pre-implementation To Post-implementation | The percentage of participants with microbiologically confirmed TB who were lost to follow-up in the post-implementation "minus" The percentage of participants with microbiologically confirmed TB who were lost to follow-up in the pre-implementation | 12 Months |
| Difference in Percentage of Participants With Microbiologically Confirmed TB | Difference in the percentage of participants with microbiologically confirmed TB who initiated treatment within 7 days from post-implementation to pre-implementation at intervention arm "minus" Difference in the percentage of participants with microbiologically confirmed TB who initiated treatment within 7 days from post-implementation to pre-implementation at comparison arm | Up to 12 months post-implementation |
| Reach: Percentage of Patients Who Were Administered (or Evaluated) by PredicTB Score | Percentage of patients who were administered (or evaluated) by PredicTB score among those who presented presumptive TB symptoms at clinics in the post-implementation period in intervention arm | Up to 12 months |
| Adoption: Percentage of Providers Adopting PredicTB | Percentage of providers using PredicTB in over 50% of encounters in which sputum is submitted for pulmonary TB diagnosis among those seeing >5 patients who submit sputum for diagnosis of pulmonary TB | Month 18 |
| Maintenance: Change in Effectiveness Over Time in the Post-implementation Phase at Intervention Arm | Percentage of participants with microbiologically confirmed TB who initiated treatment within seven days in the post-implementation phase at intervention arm "minus" Percentage of participants with microbiologically confirmed TB who initiated treatment within seven days in the post-implementation phase at intervention arm | Up to 12 months |
| Modeled Changes in 5-year Mortality With PredicTB | Modeled hypothetical, expected changes in mortality at year 5, comparing simulations in which PredicTB is implemented to those in which PredicTB is not implemented, using a Markov state-transition model | Month 12 |
| BG001 | Control Arm | The standard of care will be conducted in this arm. |
| BG002 | Total | Total of all reporting groups |
| Clinics |
|
| years |
| Participants |
|
|
| Sex: Female, Male | One missing in sex at control arm | Count of Participants | Participants | Participants |
|
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants | Participants |
|
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| Region of Enrollment | Count of Participants | Participants | Participants |
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| HIV status | Count of Participants | Participants | Participants |
|
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| Sputum specimen submitted | Count of Participants | Participants | Participants |
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| Microbiologically confirmed TB | Count of Participants | Participants | Participants |
|
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| OG001 | Control Arm | The standard of care will be conducted in this arm. |
|
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| Primary | Implementation: Percentage of Encountered Patients at Intervention Arm Who Initiated the Same-day Treatment Based on PredicTB Score as Indicated | Percentage of patients who initiated same-day treatment divided by the number of patients who had a higher PredicTB score than the clinic-specific score of treatment threshold in the post-implementation period in intervention arm | This outcome includes individuals who presented TB symptoms. This outcome is relevant to intervention arm only. | Posted | Number | percentage of participants | Up to 12 months |
|
|
|
| Secondary | Incremental Cost-effectiveness of PredicTB | (cost of implementing PredicTB - cost of standard of care)/(projected disability-adjusted life years (DALYs) in standard of care - projected DALYs with PredicTB) | Data was not collected. | Posted | Months 0 - 12 |
|
|
| Secondary | Difference in TB Mortality From Pre-implementation to Post-implementation | The percentage of participants with microbiologically confirmed TB who died of any cause in the post-implementation "minus" The percentage of participants with microbiologically confirmed TB who died of any cause in the pre-implementation | This outcome includes individuals who were diagnosed with tuberculosis. | Posted | Number | 95% Confidence Interval | percentage of participants | 12 Months |
|
|
|
| Secondary | Difference in Loss to Care From Pre-implementation To Post-implementation | The percentage of participants with microbiologically confirmed TB who were lost to follow-up in the post-implementation "minus" The percentage of participants with microbiologically confirmed TB who were lost to follow-up in the pre-implementation | This outcome includes individuals who were diagnosed with tuberculosis. | Posted | Number | 95% Confidence Interval | percentage of participants | 12 Months |
|
|
|
| Secondary | Difference in Percentage of Participants With Microbiologically Confirmed TB | Difference in the percentage of participants with microbiologically confirmed TB who initiated treatment within 7 days from post-implementation to pre-implementation at intervention arm "minus" Difference in the percentage of participants with microbiologically confirmed TB who initiated treatment within 7 days from post-implementation to pre-implementation at comparison arm | This outcome includes individuals who were diagnosed with tuberculosis. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 12 months post-implementation |
|
|
|
| Secondary | Reach: Percentage of Patients Who Were Administered (or Evaluated) by PredicTB Score | Percentage of patients who were administered (or evaluated) by PredicTB score among those who presented presumptive TB symptoms at clinics in the post-implementation period in intervention arm | This outcome includes individuals who presented TB symptoms. This outcome is relevant to intervention arm only. | Posted | Number | percentage of participants | Up to 12 months |
|
|
|
| Secondary | Adoption: Percentage of Providers Adopting PredicTB | Percentage of providers using PredicTB in over 50% of encounters in which sputum is submitted for pulmonary TB diagnosis among those seeing >5 patients who submit sputum for diagnosis of pulmonary TB | This outcome analysis is relevant to intervention arm only. Per protocol, healthcare providers were not considered enrolled. | Posted | Number | percentage of providers | Month 18 |
|
|
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| Secondary | Maintenance: Change in Effectiveness Over Time in the Post-implementation Phase at Intervention Arm | Percentage of participants with microbiologically confirmed TB who initiated treatment within seven days in the post-implementation phase at intervention arm "minus" Percentage of participants with microbiologically confirmed TB who initiated treatment within seven days in the post-implementation phase at intervention arm | This outcome is relevant to intervention arm only | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 12 months |
|
|
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| Secondary | Modeled Changes in 5-year Mortality With PredicTB | Modeled hypothetical, expected changes in mortality at year 5, comparing simulations in which PredicTB is implemented to those in which PredicTB is not implemented, using a Markov state-transition model | Data was not collected. | Posted | Month 12 |
|
|
| 12 |
| 316 |
| 0 |
| 316 |
| 0 |
| 316 |
| EG001 | Control Arm | The standard of care will be conducted in this arm. | 17 | 211 | 0 | 211 | 0 | 211 |
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| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D012141 | Respiratory Tract Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| Unknown/Missing |
|