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

Frailty Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04743063
• Other study ID #: 2019P000110-ARNI
• Status: Active, not recruiting
• Start date: January 14, 2021
• Est. completion date: December 31, 2022

Study information

• Verified date: February 2021
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40000
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Frailty
• Heart Failure
• Heart Failure, Systolic

Intervention

Drug:
• sacubitril/valsartan
Initiation of sacubitril/valsartan, identified using prescription fill in pharmacy claims
• Angiotensin II Receptor Blockers
Initiation of ARBs, identified using prescription fill in pharmacy claims

Locations

Country	Name	City	State
United States	Brigham And Women's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with composite events of death or heart failure hospitalization	All-cause mortality OR heart failure hospitalization	July 2015 - December 2020
Primary	Number of patients with composite serious adverse events	Hypotension OR acute kidney injury/acute kidney failure OR hyperkalemia OR angioedema	July 2015 - December 2020
Secondary	Number of patients with all-cause mortality	All-cause mortality is defined by the National Death Index file or vital status information in the claims dataset.	July 2015 - December 2020
Secondary	Number of patients with heart failure hospitalization	Heart failure hospitalization is defined as any hospitalization with relevant diagnosis codes in the primary position.	July 2015 - December 2020
Secondary	Number of patients with hypotension	Hypotension is defined as any hospitalization or Emergency Department visit with relevant diagnosis codes in the primary position.	July 2015 - December 2020
Secondary	Number of patients with hyperkalemia	Hyperkalemia is defined as any hospitalization or Emergency Department visit with relevant diagnosis codes in the primary position.	July 2015 - December 2020
Secondary	Number of patients with acute kidney injury/acute kidney failure	Acute kidney injury/Acute kidney failure is defined as any hospitalization or Emergency Department visit with relevant diagnosis codes in the primary position.	July 2015 - December 2020
Secondary	Number of patients with angioedema	Angioedema is defined as any hospitalization or Emergency Department visit with relevant diagnosis codes in the primary position.	July 2015 - December 2020