Clinical trial NCT04743063: Prospective Monitoring of Angiotensin Receptor Neprilysin Inhibitor in Older Adults With Heart Failure and Frailty
Official title: Prospective Monitoring of Angiotensin Receptor Neprilysin Inhibitor in Older Adults With Heart Failure and Frailty
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Heart Failure, Systolic
Frailty
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2021-02-08
Enrollment: 40000
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Study population includes older patients with heart failure with reduced ejection fraction who initiates an angiotensin receptor neprilysin inhibitor or an angiotensin II receptor blocker.

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).

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.

Primary outcomes:
measure: Number of patients with composite events of death or heart failure hospitalization
timeFrame: July 2015 - December 2020
measure: Number of patients with composite serious adverse events
timeFrame: July 2015 - December 2020
Secondary outcomes:
measure: Number of patients with all-cause mortality
timeFrame: July 2015 - December 2020
measure: Number of patients with heart failure hospitalization
timeFrame: July 2015 - December 2020
measure: Number of patients with hypotension
timeFrame: July 2015 - December 2020
measure: Number of patients with hyperkalemia
timeFrame: July 2015 - December 2020
measure: Number of patients with acute kidney injury/acute kidney failure
timeFrame: July 2015 - December 2020
measure: Number of patients with angioedema
timeFrame: July 2015 - December 2020
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham And Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Dae Hyun Kim, MD, MPH, ScD
role: PRINCIPAL_INVESTIGATOR
References: