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

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ClinicalTrials.gov Identifier: NCT04757584
Recruitment Status : Enrolling by invitation
First Posted : February 17, 2021
Last Update Posted : June 25, 2021
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Weill Medical College of Cornell University

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

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : April 1, 2021
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine


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




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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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



Information from the National Library of Medicine

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04757584


Locations
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United States, New York
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
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Principal Investigator: Parag Goyal, MD Weill Medical College of Cornell University
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Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT04757584    
Other Study ID Numbers: 19-10020922-01
K76AG064428 ( U.S. NIH Grant/Contract )
First Posted: February 17, 2021    Key Record Dates
Last Update Posted: June 25, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Heart Failure
Heart Diseases
Heart Failure, Diastolic
Cardiovascular Diseases
Propranolol
Metoprolol
Atenolol
Sotalol
Nadolol
Acebutolol
Carvedilol
Nebivolol
Bisoprolol
Labetalol
Pindolol
Betaxolol
Penbutolol
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Vasodilator Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic beta-1 Receptor Antagonists