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

NCT04757584 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: 19-10020922-01K76AG064428
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (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

  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)

Study Arms (2)

Beta Blocker ABAB Sequence

ACTIVE COMPARATOR

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

Beta Blocker BABA Sequence

ACTIVE COMPARATOR

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

Interventions

Beta blockers 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.

Also known as: atenolol, betaxolol, bisoprolol, metoprolol, nebivolol, nadolol, propranolol, acebutolol, penbutolol, pindolol, carvedilol, labetalol, sotalol, metoprolol succinate, metoprolol tartrate

Beta Blocker ABAB Sequence; Beta Blocker BABA Sequence

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Weill Cornell Medicine

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Heart Failure; Heart Failure, Diastolic; Heart Diseases

Interventions

Adrenergic beta-Antagonists; Atenolol; Betaxolol; Bisoprolol; Metoprolol; Nebivolol; Nadolol; Propranolol; Acebutolol; Penbutolol; Pindolol; Carvedilol; Labetalol; Sotalol

Condition Hierarchy (Ancestors)

Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Ethanolamines; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 3-Ring; Salicylamides; Amides

Results Point of Contact

• Title: Maryam Hyder
• Organization: Weill Cornell Medicine

mah4022@med.cornell.edu

646-962-5904

Study Officials

• Parag Goyal, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2021
• First Posted: February 17, 2021
• Study Start: April 1, 2021
• Primary Completion: April 28, 2023
• Study Completion: April 28, 2023
• Last Updated: April 9, 2024
• Results First Posted: April 9, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)