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

NCT ID: NCT04757584

Last Updated: 2024-04-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-01
• Study Completion Date: 2023-04-28

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Beta blockers

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

Beta blockers

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

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

Eligibility Criteria

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

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Parag Goyal, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Weill Cornell Medicine

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

K76AG064428

Identifier Type: NIH

Identifier Source: secondary_id

View Link

19-10020922-01

Identifier Type: -

Identifier Source: org_study_id