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

Primary Purpose

Heart Failure, Heart Failure, Diastolic, Heart Failure With Preserved Ejection Fraction

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Beta blockers
Sponsored by
Weill Medical College of Cornell University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Heart Failure

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Weill Cornell Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Beta Blocker ABAB Sequence

Beta Blocker BABA Sequence

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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
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
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
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
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

Secondary Outcome Measures

Full Information

First Posted
February 12, 2021
Last Updated
May 9, 2023
Sponsor
Weill Medical College of Cornell University
Collaborators
National Institute on Aging (NIA)
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1. Study Identification

Unique Protocol Identification Number
NCT04757584
Brief Title
Pilot Deprescribing N-of-1 Trials for Beta-blockers in HFpEF
Official Title
N-of-1 Trials for Deprescribing Beta-blockers in HFpEF
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
April 1, 2021 (Actual)
Primary Completion Date
April 28, 2023 (Actual)
Study Completion Date
April 28, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Weill Medical College of Cornell University
Collaborators
National Institute on Aging (NIA)

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Heart Failure, Diastolic, Heart Failure With Preserved Ejection Fraction, Cardiac Failure, Heart Disease

7. Study Design

Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Beta Blocker ABAB Sequence
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Beta Blocker BABA Sequence
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Beta blockers
Other Intervention Name(s)
atenolol, betaxolol, bisoprolol, metoprolol, nebivolol, nadolol, propranolol, acebutolol, penbutolol, pindolol, carvedilol, labetalol, sotalol, metoprolol succinate, metoprolol tartrate
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Description
This will be assessed by open-ended questions in a qualitative interview format
Time Frame
Baseline
Title
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
Description
The understandability of study instructions and usability of study materials will be assessed by open-ended questions in a qualitative interview format
Time Frame
At the end of intervention arm 1 (week 6)
Title
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
Description
The understandability of study instructions and usability of study materials will be assessed by open-ended questions in a qualitative interview format
Time Frame
At the end of intervention arm 2 (week 12)
Title
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
Description
The understandability of study instructions and usability of study materials will be assessed by open-ended questions in a qualitative interview format
Time Frame
At the end of intervention arm 3 (week 18)
Title
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
Description
The understandability of study instructions and usability of study materials will be assessed by open-ended questions in a qualitative interview format
Time Frame
At the end of intervention arm 4 (week 24)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Parag Goyal, MD
Organizational Affiliation
Weill Medical College of Cornell University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Weill Cornell Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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