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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
| Rutgers University | OTHER |
| Johns Hopkins University | OTHER |
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This study aims to evaluate the comparative risk of dementia/Alzheimer's disease onset between patients treated with medications that target specific metabolic pathways and patients treated with alternative medications for the same indication.
This is a non-randomized, non-interventional study that is part of the DREAM Study of Brigham and Women's Hospital. DREAM is led by Dr. Madhav Thambisetty, MD, PhD, Chief of the Clinical and Translational Neuroscience Section, Laboratory of Behavioral Neuroscience, National Institute on Aging (NIA) intramural research program. This study aims to evaluate the comparative risk of dementia/Alzheimer's disease onset between patients treated with medications that target specific metabolic pathways and patients treated with alternative medications for the same indication using healthcare claims data.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PDE5 inhibitors | Exposure group |
| |
| Endothelin receptor antagonists | Reference group |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PDE5 inhibitor | Drug | PDE5 inhibitors (sildenafil, tadalafil) claim is used as the exposure group. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to Dementia Onset | Time to dementia onset includes: Alzheimer's disease, vascular dementia, senile, presenile, or unspecified dementia, or dementia in other diseases classified elsewhere. Please refer to uploaded protocol for full definition. Analysis 1-'as-treated' follow-up approach: In this approach, we followed patients from cohort entry until treatment discontinuation or switch to the comparator treatment, insurance disenrollment, death, or administrative endpoint (December 2018). Treatment discontinuation was defined as occurring 90 days after the expected days supply. of the most recently filled prescription to accommodate suboptimal adherence during treatment periods. Analysis 2-'as-started' follow-up approach incorporating a 6-month 'induction' period. Analysis 3-incorporating a 6-month 'symptoms to diagnosis' period Analysis 4-high-specificity outcome definition Study accessed Medicare files (Jan 2008-Dec 2018) between September 1, 2021 to October 4, 2022. | Median follow up times: 1) 168 days (exp), 151 days (ref) 2) 693 days (exp), 720 days (ref) 3) 382 days (exp), 358 days (ref) 4) 169 days (exp), 151 days (ref) |
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Please see https://docs.google.com/spreadsheets/d/19NwmDi8xwWjzXqhSLPDTg4CKHt5UDQXuwCnZwY8jCS8/edit?usp=sharing or Appendix A for full code and algorithm definitions.
Medicare timeframe: 2008 to 2018 (end of data availability).
Inclusion Criteria:
Exclusion Criteria:
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This study will employ a new user, active comparator, observational cohort study design comparing PDE5 inhibitors (sildenafil, tadalafil) to endothelin receptor antagonists (bosentan, ambrisentan, macitentan). The patients will be required to have continuous enrollment during the baseline period of 365 days before initiation of study drugs (cohort entry/index date). Follow-up for the outcome (dementia) differs between analyses. Follow-up begins the day after drug initiation (analysis 1, 3, 4); 180 days after drug initiation (analysis 2).
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| Name | Affiliation | Role |
|---|---|---|
| Madhav Thambisetty, MD, PhD | National Institute on Aging (NIA) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital | Boston | Massachusetts | 02120 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | PDE5 Inhibitors | Exposure group PDE5 inhibitor: PDE5 inhibitors (sildenafil, tadalafil) claim is used as the exposure group. |
| FG001 | Endothelin Receptor Antagonists | Reference group Endothelin Receptor Antagonists: Endothelin receptor antagonists (bosentan, ambrisentan, macitentan) claim is used as the reference group. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Study cohort after 1:1 propensity score matching
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| ID | Title | Description |
|---|---|---|
| BG000 | PDE5 Inhibitors | Exposure group PDE5 inhibitor: PDE5 inhibitors (sildenafil, tadalafil) claim is used as the exposure group. |
| BG001 | Endothelin Receptor Antagonists | Reference group Endothelin Receptor Antagonists: Endothelin receptor antagonists (bosentan, ambrisentan, macitentan) claim is used as the reference group. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Time to Dementia Onset | Time to dementia onset includes: Alzheimer's disease, vascular dementia, senile, presenile, or unspecified dementia, or dementia in other diseases classified elsewhere. Please refer to uploaded protocol for full definition. Analysis 1-'as-treated' follow-up approach: In this approach, we followed patients from cohort entry until treatment discontinuation or switch to the comparator treatment, insurance disenrollment, death, or administrative endpoint (December 2018). Treatment discontinuation was defined as occurring 90 days after the expected days supply. of the most recently filled prescription to accommodate suboptimal adherence during treatment periods. Analysis 2-'as-started' follow-up approach incorporating a 6-month 'induction' period. Analysis 3-incorporating a 6-month 'symptoms to diagnosis' period Analysis 4-high-specificity outcome definition Study accessed Medicare files (Jan 2008-Dec 2018) between September 1, 2021 to October 4, 2022. | Study cohort after 1:1 propensity score matching | Posted | Number | 95% Confidence Interval | Incidence rate per 1000 person year | Median follow up times: 1) 168 days (exp), 151 days (ref) 2) 693 days (exp), 720 days (ref) 3) 382 days (exp), 358 days (ref) 4) 169 days (exp), 151 days (ref) |
'As-treated' follow-up approach - Median follow-up days of 168 (for PDE5 inihibitors) and 151 (for endothelin receptor antagonists)
Our study did not capture Serious Adverse Events.
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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 | PDE5 Inhibitors | Exposure group PDE5 inhibitor: PDE5 inhibitors (sildenafil, tadalafil) claim is used as the exposure group. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Rishi J Desai, PhD | Brigham and Women's Hospital | 617-278-0932 | rdesai@bwh.harvard.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 | Oct 27, 2021 | Oct 27, 2021 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D000081029 | Pulmonary Arterial Hypertension |
| ID | Term |
|---|---|
| D006976 | Hypertension, Pulmonary |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D058986 | Phosphodiesterase 5 Inhibitors |
| D065128 | Endothelin Receptor Antagonists |
| ID | Term |
|---|---|
| D010726 | Phosphodiesterase Inhibitors |
| D004791 | Enzyme Inhibitors |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
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| Endothelin Receptor Antagonists | Drug | Endothelin receptor antagonists (bosentan, ambrisentan, macitentan) claim is used as the reference group. |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Dementia risk factors | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | PDE5 Inhibitors | Exposure group PDE5 inhibitor: PDE5 inhibitors (sildenafil, tadalafil) claim is used as the exposure group. |
| OG001 | Endothelin Receptor Antagonists | Reference group Endothelin Receptor Antagonists: Endothelin receptor antagonists (bosentan, ambrisentan, macitentan) claim is used as the reference group. |
|
|
| 327 |
| 2,888 |
| 0 |
| 0 |
| 0 |
| 2,888 |
| EG001 | Endothelin Receptor Antagonists | Reference group Endothelin Receptor Antagonists: Endothelin receptor antagonists (bosentan, ambrisentan, macitentan) claim is used as the reference group. | 407 | 2,888 | 0 | 0 | 0 | 2,888 |
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| D020164 | Chemical Actions and Uses |