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

Phase 4

Completed

Conditions: Heart Failure
Heart Failure, Diastolic
Heart Failure With Preserved Ejection Fraction
Cardiac Failure
Heart Disease

Interventions: Drug: Beta blockers

Registration Number: NCT04757584

Lead Sponsor: Weill Medical College of Cornell University

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 9

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 & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Beta Blocker ABAB Sequence	Beta blockers	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.
Beta Blocker BABA Sequence	Beta blockers	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.

Primary Outcome Measures

Name	Time	Method
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	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)	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.

Secondary Outcome Measures