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

Study Overview
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Brief Summary
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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.

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

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

Intervention / Treatment
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* Drug: Beta blockers


Participation Criteria
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Eligibility Criteria
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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: Severe valvular disease Constrictive pericarditis High output heart failure Infiltrative cardiomyopathy Other compelling indication for beta blocker: Prior EF < 50% Hypertrophic cardiomyopathy Angina symptoms Acute coronary syndrome, myocardial infarction or coronary artery bypass surgery in prior 3 year History of ventricular tachycardia Atrial arrhythmia with hospitalization for rapid ventricular response, prior 1 year 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) Decompensated HF Hospitalized in past 30 days 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

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Beta Blocker ABAB Sequence<br>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. During Period 3, they will restart beta-blockers, gradually uptitrating until reaching their home dose and finally during period 4, we will again conduct a dose reduction until off of beta blockers. | Drug: Beta blockers<br>* The intervention is a two-arm crossover withdrawal/ reversal design (On [A] vs Off [B]) with 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.<br>* Other names: metoprolol tartrate;|
| Active Comparator: Beta Blocker BABA Sequence<br>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. During Period 3, we will again conduct a dose reduction, until the subject is off of beta blockers and finally during Period 4, we will uptitrate them back to their home dose of beta blockers. | Drug: Beta blockers<br>* The intervention is a two-arm crossover withdrawal/ reversal design (On [A] vs Off [B]) with 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.<br>* Other names: metoprolol tartrate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | This will be assessed by open-ended questions in a qualitative interview format | 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 | The understandability of study instructions and usability of study materials will be assessed by open-ended questions in a qualitative interview format | At the end of intervention arm 1 (week 6) | 
| 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 understandability of study instructions and usability of study materials will be assessed by open-ended questions in a qualitative interview format | At the end of intervention arm 2 (week 12) | 
| 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 understandability of study instructions and usability of study materials will be assessed by open-ended questions in a qualitative interview format | At the end of intervention arm 3 (week 18) | 
| 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 understandability of study instructions and usability of study materials will be assessed by open-ended questions in a qualitative interview format | At the end of intervention arm 4 (week 24) |