Data Analysis for Drug Repurposing for Effective Alzheimer's Medicines (DREAM) - PDE5 Inhibitors vs Endothelin Receptor Antagonist

Completed

• Conditions: Pulmonary Arterial Hypertension
• Interventions: Drug: PDE5 inhibitor; Drug: Endothelin Receptor Antagonists

• Registration Number: NCT05039086
• Lead Sponsor: Brigham and Women's Hospital

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2021-09-01
• Study First Submitted: 2021-09-01
• Study First Submitted QC: 2021-09-01
• Study First Posted: 2021-09-09
• Primary Completion: 2021-09-30
• Study Completion: 2022-10-04
• Results First Submitted: 2023-09-11
• Results First Submitted QC: 2024-01-25
• Results First Posted: 2024-02-20
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-09
• Last Update Posted: 2024-04-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13021

Inclusion Criteria

• 1. Aged > 65 years on the index date
• 2. No prior use of PDE5 inhibitors (sildenafil, tadalafil) and endothelin receptor antagonists (bosentan, ambrisentan, macitentan) anytime prior to cohort entry date
• 3. Enrollment in Medicare Part A, B, and D with no HMO coverage for 365 days prior to and including cohort entry date

Exclusion Criteria

• 1. Prior history of dementia measured anytime prior to cohort entry date
• 2. No prior history of pulmonary arterial hypertension recorded in the 365 days prior to cohort entry date
• 3. Prior history of nursing home admission in the 365 days prior to the cohort entry date

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
PDE5 inhibitors	PDE5 inhibitor	Exposure group
Endothelin receptor antagonists	Endothelin Receptor Antagonists	Reference group

Primary Outcome Measures

Name	Time	Method
Time to Dementia Onset	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)	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.

Trial Locations

Locations (1)

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States