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

• Sponsor: Weill Medical College of Cornell University (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04757584
• Collaborator: National Institute on Aging (NIA) (NIH)
• Enrollment: 16
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 29
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure; Heart Failure, Diastolic; Heart Failure With Preserved Ejection Fraction; Cardiac Failure; Heart Disease	Drug: Beta blockers	Phase 4

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: N-of-1 Trials for Deprescribing Beta-blockers in HFpEF
• Actual Study Start Date: Apr 1, 2021
• Anticipated Primary Completion Date: Dec 1, 2022
• Anticipated Study Completion Date: Sep 1, 2023

Arms and Interventions

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. 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; 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.; Other Names: atenolol betaxolol bisoprolol metoprolol nebivolol nadolol propranolol acebutolol penbutolol pindolol carvedilol labetalol sotalol metoprolol succinate 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. 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; 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.; Other Names: atenolol betaxolol bisoprolol metoprolol nebivolol nadolol propranolol acebutolol penbutolol pindolol carvedilol labetalol sotalol metoprolol succinate metoprolol tartrate

Outcome Measures

Primary Outcome Measures

1. 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 [Baseline]

   This will be assessed by open-ended questions in a qualitative interview format

2. 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 [At the end of intervention arm 1 (week 6)]

   The understandability of study instructions and usability of study materials will be assessed by open-ended questions in a qualitative interview format

3. 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 [At the end of intervention arm 2 (week 12)]

   The understandability of study instructions and usability of study materials will be assessed by open-ended questions in a qualitative interview format

4. 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 [At the end of intervention arm 3 (week 18)]

   The understandability of study instructions and usability of study materials will be assessed by open-ended questions in a qualitative interview format

5. 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 [At the end of intervention arm 4 (week 24)]

   The understandability of study instructions and usability of study materials will be assessed by open-ended questions in a qualitative interview format

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Weill Cornell Medicine	New York	New York	United States	10065

Sponsors and Collaborators

• Weill Medical College of Cornell University
• National Institute on Aging (NIA)

Investigators

• Principal Investigator: Parag Goyal, MD, Weill Medical College of Cornell University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT04757584
• Other Study ID Numbers: 19-10020922-01; K76AG064428
• First Posted: Feb 17, 2021
• Last Update Posted: Jun 28, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Additional relevant MeSH terms: Heart Failure; Heart Diseases; Heart Failure, Diastolic; Propranolol; Metoprolol; Atenolol; Sotalol; Nadolol; Acebutolol; Carvedilol; Nebivolol; Bisoprolol; Labetalol; Pindolol; Betaxolol; Penbutolol; Adrenergic beta-Antagonists

Study Results

No Results Posted as of Jun 28, 2022