Pilot Deprescribing N-of-1 Trials for Beta-blockers in HFpEF

N-of-1 Trials for Deprescribing Beta-blockers in HFpEF

In this study, we will test the feasibility of N-of-1 trials for deprescribing beta-blockers in patients with Heart Failure with Preserved Ejection Fraction. To achieve this objective we will conduct 16 4-period N-of-1 trials (on vs. off) and subsequently interview participants to better understand feasibility and pragmatism. The N-of-1 trials will be iteratively refined in real-time based on this feedback.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Heart Disease; Heart Failure, Diastolic; Heart Failure With Preserved Ejection Fraction; Cardiac Failure
• Intervention / Treatment: Drug: Beta blockers

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ambulatory adults ≥65 years of age with Heart Failure with Preserved Ejection Fraction (HFpEF) according to ACC/AHA guidelines: (signs and symptoms of Heart failure [HF] and ejection fraction [EF] ≥50%)
• Taking Beta blocker

Exclusion Criteria:

• Alternate Causes of HFpEF Syndrome:

  1. Severe valvular disease
  2. Constrictive pericarditis
  3. High output heart failure
  4. Infiltrative cardiomyopathy

• Other compelling indication for beta blocker:

  1. Prior EF < 50%
  2. Hypertrophic cardiomyopathy
  3. Angina symptoms
  4. Acute coronary syndrome, myocardial infarction or coronary artery bypass surgery in prior 3 year
  5. History of ventricular tachycardia
  6. Atrial arrhythmia with hospitalization for rapid ventricular response, prior 1 year
  7. Sinus tachycardia > 100 beats per minute (bpm), atrial arrhythmia with ventricular rate >90 bpm, systolic blood pressure > 160 mmHg

• Clinical instability (N-of-1 trials are appropriate for stable conditions only)

  1. Decompensated HF
  2. Hospitalized in past 30 days
  3. Medication changes or procedures in prior 14 days (to prevent confounding from other interventions), at PI discretion
• Estimated life expectancy <6 months
• Moderate-severe dementia or psychiatric disorder precluding informed consent
• Any condition that, in Principal Investigator's opinion, makes the patient unsuitable for study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Beta Blocker ABAB Sequence; This arm will follow an ABAB sequence. "A" representing ON beta blockers and "B" representing OFF beta blockers. Subjects in this arm will continue their home dose during the initial A period, they will then crossover into Period 2, where dose reduction will begin until they are off of beta blockers. After Period 2, the subjects have the option to decide if they want to be on or off their beta blocker and proceed with the Follow-Up Phase, or continue to Period 3 if they don't feel ready to make that decision to stay on or go off their beta blocker yet. During Period 3, they will restart beta-blockers, gradually up-titrating until reaching their home dose. Finally, during Period 4, we will again conduct a dose reduction until off of beta blockers.	Drug: Beta blockers; The intervention is a two-arm crossover withdrawal/ reversal design (On [A] vs Off [B]) with up to 4 periods, each period lasting up to 6 weeks. During the On period (A), subjects will be on their beta blocker. During the Off period (B), their beta blockers will be down-titrated and subsequently discontinued. Subjects will be randomized into either ABAB or BABA sequences.; Other Names: sotalol; propranolol; labetalol; nebivolol; metoprolol succinate; metoprolol; acebutolol; atenolol; betaxolol; bisoprolol; pindolol; penbutolol; carvedilol; nadolol; metoprolol tartrate
Active Comparator: Beta Blocker BABA Sequence; This arm will follow a BABA sequence. "A" representing ON beta blockers and "B" representing OFF of beta blockers. Subjects in this arm will have their previously prescribed beta blocker dose reduced until they are completely off of beta blockers during Period 1. They will then crossover into Period 2, where uptitration will begin until they are back on their previously prescribed dose of beta blockers. After Period 2, the subjects have the option to decide if they want to be on or off their beta blocker and proceed with the Follow-Up Phase, or continue to Period 3 if they don't feel ready to make that decision to stay on or go off their beta blocker yet. During Period 3, we will again conduct a dose reduction, until the subject is off of beta blockers. Finally, during Period 4, we will up-titrate them back to their home dose of beta blockers.	Drug: Beta blockers; The intervention is a two-arm crossover withdrawal/ reversal design (On [A] vs Off [B]) with up to 4 periods, each period lasting up to 6 weeks. During the On period (A), subjects will be on their beta blocker. During the Off period (B), their beta blockers will be down-titrated and subsequently discontinued. Subjects will be randomized into either ABAB or BABA sequences.; Other Names: sotalol; propranolol; labetalol; nebivolol; metoprolol succinate; metoprolol; acebutolol; atenolol; betaxolol; bisoprolol; pindolol; penbutolol; carvedilol; nadolol; metoprolol tartrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Features of a Feasible and Pragmatic Protocol for Deprescribing N-of-1 Trials in Patients With Heart Failure With Preserved Ejection Fraction, as Measured by Qualitative Interview	Qualitative interviews were conducted to assess the feasibility and acceptability of deprescribing N-of-1 trials and participant experiences. Directed content analysis methods were used to develop relevant categories and themes from interview transcript data. Transcripts were coded and analyzed by two team members, consulting additional members to establish consensus where needed. Inter-rater reliability between coders was established.	Baseline
Features of a Feasible and Pragmatic Protocol for Deprescribing N-of-1 Trials in Patients With Heart Failure With Preserved Ejection Fraction, as Measured by Qualitative Interview	Qualitative interviews were conducted to assess the feasibility and acceptability of deprescribing N-of-1 trials and participant experiences. Directed content analysis methods were used to develop relevant categories and themes from interview transcript data. Transcripts were coded and analyzed by two team members, consulting additional members to establish consensus where needed. Inter-rater reliability between coders was established. The outcome measure data is the cumulative count of subjects who identified categories and themes from interview transcript data collected during the span of the outcome measure time frame, up to 6 times over 36 weeks.	The maximum amount of time a subject could have been assessed for this outcome measure is 6 times across 36 weeks. This outcome was measured at each end of period visit (weeks 6, 12, 18, 24, 30) and at the end of intervention (weeks 12, 18, 24, 30, or 36)

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Parag Goyal, MD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Actual): April 28, 2023
• Study Completion (Actual): April 28, 2023

Study Registration Dates

• First Submitted: February 12, 2021
• First Submitted That Met QC Criteria: February 12, 2021
• First Posted (Actual): February 17, 2021

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Failure; Heart Diseases; Heart Failure, Diastolic; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Adrenergic Agonists; Membrane Transport Modulators; Serotonin Agents; Serotonin Antagonists; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Antioxidants; Adrenergic beta-Agonists; Sympathomimetics; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-1 Receptor Agonists; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Propranolol; Bisoprolol; Nebivolol; Metoprolol; Carvedilol; Nadolol; Labetalol; Sotalol; Atenolol; Adrenergic beta-Antagonists; Pindolol; Betaxolol; Acebutolol; Penbutolol
• Other Study ID Numbers: 19-10020922-01; K76AG064428 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes