Prospective Monitoring of Angiotensin Receptor Neprilysin Inhibitor in Older Adults With Heart Failure and Frailty

NCT ID: NCT04743063

Last Updated: 2021-02-15

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 40000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-01-14
• Study Completion Date: 2022-12-31

Brief Summary

The objective of this study is to establish a near-real-time prospective monitoring program in Medicare, Optum and MarketScan Research data to evaluate the benefit of new cardiovascular disease (CVD) drugs for older adults with frailty. Prospective monitoring program seeks to find early effectiveness and safety signals of new drugs by updating the analysis at regular intervals as new Medicare data become available. This study specifically aims to emulate a prospective surveillance of the effectiveness and safety of Angiotensin Receptor Neprilysin Inhibitor(ARNI) vs. a comparator, Angiotensin II Receptor Blockers (ARBs), in older adults with Heart Failure with Reduced Ejection Fraction (HFrEF) and different frailty status. This program will be enhanced by incorporating a novel claims-based frailty index, which has been shown useful in assessing how the benefits and harms of drug therapy vary by frailty.

Detailed Description

Data sources of use for this study are: Medicare Database, Optum Database, and MarketScan Research Database. All data from years 2014-2020 will be included in the study.

This study follows a sequential cohort monitoring design. The monitoring analysis will include 1) retrospective analysis of available data (2015-2017) at the time of first analysis (January 2021) and 2) prospective analysis of new data (2018-2020) as they become available to the researchers. Within each database, we will emulate biannual updating of data by creating a propensity score (PS)-matched cohort of new users every 6-month interval, beginning on the first marketing of ARNI (July 7, 2015-December 31, 2015, and 6-month intervals afterwards). Each sequential cohort will be followed for development of the outcomes of interest. Outcome analysis will be performed at a pre-specified 6-month interval (prospective analysis). The surveillance will be performed by frailty status (frail vs non-frail) at the time of drug initiation. The results from each database will be pooled using fixed-effects meta-analysis (assuming low heterogeneity across the databases).

Conditions

Heart Failure, Systolic; Frailty

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

New users of angiotensin receptor neprilysin inhibitor

sacubitril/valsartan

Intervention Type: DRUG

Initiation of sacubitril/valsartan, identified using prescription fill in pharmacy claims

New users of angiotensin II receptor blockers

Angiotensin II Receptor Blockers

Intervention Type: DRUG

Initiation of ARBs, identified using prescription fill in pharmacy claims

Interventions

sacubitril/valsartan

Initiation of sacubitril/valsartan, identified using prescription fill in pharmacy claims

Intervention Type: DRUG

Angiotensin II Receptor Blockers

Initiation of ARBs, identified using prescription fill in pharmacy claims

Intervention Type: DRUG

Other Intervention Names

azilsartan; candesartan; eprosartan; Irbesartan; losartan; Olmesartan; telmisartan; valsartan

Eligibility Criteria

Inclusion Criteria

• Continuous enrollment for medical and drug insurance (e.g., Medicare Part A, B, and D) in [-365, 0] days
• Diagnosis of Heart Failure either two outpatient diagnosis or one inpatient diagnosis in [-365, 0] days
• Reduced Ejection Fraction < 45% identified using a validated claims-based algorithm in [-365, 0] days

• Day 0 is the initiation date of the study drug.

Exclusion Criteria

• No prior use of Angiotensin receptor neprilysin inhibitor or angiotensin II receptor blocker in [-365, -1] days
• No recent HF hospitalization, defined as HF diagnosis (defined in attached protocol) in the primary position in the inpatient dataset in [-60, 0] days
• No recent nursing facility stay (defined in attached protocol) for [-60, 0] days
• Age < 65 years
• Exposure to both drugs on day 0
• Contraindication to either drug (exclusion assessment window: [-60, 0] days, unless specified otherwise; algorithms specified in attached protocol)

Note: If a patient meets the above-mentioned eligibility criteria more than once, only the first record will be included.

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Dae Hyun Kim, MD, MPH, ScD

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dae Hyun Kim, MD, MPH, ScD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham And Women's Hospital

Boston, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

2019P000110-ARNI

Identifier Type: -

Identifier Source: org_study_id