Deprescribing Beta-Blockers in Elders With Heart Failure With Preserved Ejection Fraction (DEPRESCRIBE-HFpEF)

NCT07298993 | Enrolling By Invitation Phase 4 DMC FDA Drug

• 2 other identifiers: 24-08027899R01AG091005
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to learn whether stopping beta-blockers can help older adults with heart failure with preserved ejection fraction (HFpEF) feel better and function better. This study will test whether "deprescribing" or stopping these medications in a careful, guided way can improve symptoms and quality of life. Participants will be randomly assigned to one of two groups: Deprescribing group: Beta-blockers are gradually reduced using capsules that contain decreasing doses. Usual care group: Beta-blockers are continued at the usual dose in look-alike capsules. All participants will:

• Take study medicine for about 4 months
• Have their blood pressure and heart rate monitored
• Complete regular phone calls and questionnaires about how they are feeling This study does not involve any experimental medication. Participants active involvement in the study will last approximately 4 months. During these 4 months they will have 8 scheduled telephone visits.

Conditions

HFpEF; Heart Failure; HFpEF - Heart Failure With Preserved Ejection Fraction

Keywords

Heart Failure; Heart Failure with Preserved Ejection Fraction; HFPEF; Deprescribing

Outcome Measures

Primary Outcomes (1)

• The Hierarchical Composite Endpoint

  The primary outcome is net benefit, assessed using a hierarchical composite of four patient-centered outcomes: (1) time to death from any cause, (2) time to all-cause hospitalization, (3) ≥ 5-point difference of KCCQ-12 OSS change from baseline, and (4) ≥ 3-point difference in PROMIS Depression T-score change from baseline

  From baseline (day 0) to end of the follow-up phase (day 120)

Secondary Outcomes (2)

• The change from baseline in patient-reported physical health, as measured by the KCCQ-12

  Baseline, Day 120

• The change in patient-reported mental health, as measured by the PROMIS Depression scale

  Baseline, Day 120

Study Arms (2)

Deprescribe

PLACEBO COMPARATOR

Participants will have their beta-blocker replaced with pills that have decreasing amounts of beta-blocker until they are completely off their medicine and taking placebo pills.

Drug: Placebo (matching)

Continuation

ACTIVE COMPARATOR

Participants will continue their beta-blocker at their usual dose in capsules that look identical to those used for the deprescribe arm.

Drug: Beta-blockers

Interventions

Placebo (matching) DRUG

Beta-blocker dosage will be reduced over the course of 4 weeks until the participant is completely off of beta-blocker and transitioned to matching placebo capsules.

Also known as: Deprescribing

Deprescribe

Beta-blockers DRUG

Participants will continue their pre-enrollment beta-blocker at the same dose. The beta-blocker agent may include atenolol, bisoprolol, carvedilol, metoprolol succinate, or metoprolol tartrate. Medication will be provided in matching capsules to maintain blinding.

Also known as: Atenolol, Bisoprolol, Carvedilol, Metoprolol succinate, Metoprolol tartrate

Continuation

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ambulatory adults age ≥60 years with HFpEF (EF ≥50% based on most recent transthoracic echocardiogram)
• Hospitalized with HF in the past 24 months (defined by diagnostic codes in any position)
• Taking any of the following ß-blockers: atenolol, bisoprolol, carvedilol, metoprolol succinate, or metoprolol tartrate (i.e., pharmacy prescription data)
• Kaiser Permanence Northern California Membership

You may not qualify if:

• Alternative etiologies of HFpEF syndrome
• Compelling guideline indication for ß-blocker:
• Prior EF \<50% (i.e., based on the structured data field on transthoracic echocardiogram)
• Current anginal symptoms (i.e., based on the Rose Angina single-question screener for angina)
• MI (i.e., diagnostic codes) and/or coronary revascularization (i.e., procedure codes) within 3 years
• Hospitalization for a primary discharge diagnosis of atrial fibrillation or atrial flutter in the prior 12 months
• Other documented reason in the opinion of the treating provider and/or enrolling clinician-investigator
• Evidence of recent decompensated HF
• Hospitalization for a primary discharge diagnosis of HF within the past 30 days
• Change in loop diuretic pharmacy prescription in the past 30 days (i.e. pharmacy prescription data) (Note: This definition is based on documented prescription changes and does not include short-term dose adjustments that were verbally communicated to the patient by their provider.)
• Estimated life expectancy \<6 months (i.e., diagnostic codes)
• Diagnosed dementia (i.e.., diagnostic codes)
• Unable to provide informed consent
• Loss of Kaiser Permanence Northern California Membership

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• National Institute on Aging (NIA): collaborator
• Kaiser Foundation Research Institute: collaborator

Study Sites (1)

Kaiser Permanente Northern California (KPNC)

Pleasanton, California, 94588, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Deprescriptions; Adrenergic beta-Antagonists; Atenolol; Bisoprolol; Carvedilol; Metoprolol

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring

Study Officials

• Parag Goyal, MD, MSc

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

• Andrew Ambrosy, MD, MPH

  Kaiser Permanente

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2025
• First Posted: December 23, 2025
• Study Start: February 2, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2029
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: The data will be shared after we have published the primary results of this study. There is no end date to access the data from the research project.
• Access Criteria: Researchers granted access to the data will be required to use it solely for research purposes, ensuring that no individual participants are identifiable. They must also implement appropriate security measures, such as using password-protected servers and files, to safeguard the data. Upon completion of the analyses, the data must be returned or destroyed. Released datasets will be subject to stringent safeguards to ensure compliance with the Health Insurance Portability and Accountability Act (HIPAA). Additionally, a data-sharing agreement will be required, specifying that the data is used exclusively for research purposes and that no participants are identifiable. Any additional approvals required by participating institutions, including KPNC, will be obtained. A data management plan will also be necessary to ensure the continued security and confidentiality of the data, as well as to outline the process for returning or destroying the data once the analysis is complete.

Locations

US (1)