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Impact of Beta-blockers on Physical Function in HFpEF

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ClinicalTrials.gov Identifier: NCT04767061
Recruitment Status : Enrolling by invitation
First Posted : February 23, 2021
Last Update Posted : June 24, 2021
Sponsor:
Collaborator:
The New York Community Trust
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Brief Summary:
The purpose of this study is to understand the impact of beta-blockers on physical function in older adults with heart failure. We will achieve this objective by conducting N-of-1 trials. N-of-1 trials are personalized experiments that test different treatment options in an individual patient.

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. Change in physical activity when on beta-blocker versus when off beta-blocker, as measured by step count on wearable activity monitoring device [ Time Frame: Weeks 5-6, Weeks 11-12, Weeks 17-18, Weeks 23-24 ]
    The wearable activity monitoring device measures daily step count. We will compare average step counts over 2-week periods.

  2. Change in lower extremity function when on beta-blocker versus when off beta-blocker, as measured by Short Physical Performance Battery [ Time Frame: Baseline, Week 6, Week 12, Week 18, Week 24 ]
    The Short Physical Performance Battery assesses gait speed, core strength when rising from a chair without using upper extremities, and balance while standing without a cane or walker. Total scores range from 0 to 12, with higher scores indicating better physical performance

  3. Change in exercise capacity when on beta-blocker versus when off beta-blocker, as measured by peak oxygen consumption (VO2) during cardiopulmonary exercise test (CPET) [ Time Frame: Week 6, Week 12 ]
    Cardiopulmonary exercise testing (CPET) measures breath-by-breath oxygen production during symptom-limited exercise on a stationary bike. This permits calculation of peak oxygen consumption (VO2). Percent predicted peak VO2 for body weight will also be calculated.


Secondary Outcome Measures :
  1. Change in patient-reported quality of life when on beta-blocker versus when off beta-blocker, as measured by Patient-Reported Outcome Measurement Information System-29 (PROMIS-29) [ Time Frame: Baseline, Weekly over 24 weeks, Month 9, Month 12 ]
    Patient-Reported Outcome Measurement Information System-29 (PROMIS-29) is a health-related quality of life survey, with questions from 6 domains: depression, anxiety, physical function, pain interference, sleep disturbance, and ability to engage in social roles and activities. Questions are ranked on a 5-point Likert scale, with higher scores at times indicating better quality of life, and at other times indicating poorer quality of life. There is a pain rating scale ranging from 0 to 10, with higher scores indicating higher pain level. Scores are reported for each domain, as well as for pain rating.

  2. Change in patient-reported sexual function when on beta-blocker versus when off beta-blocker, as measured by Patient-Reported Outcome Measurement Information System-Sexual Function (PROMIS-Sexual Function) [ Time Frame: Baseline, Week 6, Week 12, Week 18, Week 24, Month 9, Month 12 ]
    Patient-Reported Outcome Measurement Information System-Sexual Function (PROMIS-Sexual Function) measures self-reported sexual function and satisfaction. Questions are ranked on a 6-point Likert scale, with higher scores indicating poorer sexual function and satisfaction.

  3. Change in patient-reported cognitive function when on beta-blocker versus when off beta-blocker, as measured by Patient-Reported Outcome Measurement Information System-Short Form 6a (PROMIS SF-6a) [ Time Frame: Baseline, Weekly over 24 weeks, Month 9, Month 12 ]
    Patient-Reported Outcome Measurement Information System-Short Form 6a (PROMIS SF-6a) is a survey of patient-perceived cognitive deficits. Questions are ranked on a 5-point Likert scale, with higher scores indicating poorer cognitive function.

  4. Change in patient-reported health status when on beta-blocker versus when off beta-blocker, as measured by Kansas City Cardiomyopathy Questionnaire (KCCQ-12) [ Time Frame: Baseline, Biweekly over 24 weeks, Month 9, Month 12 ]
    The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a heart failure-specific health status survey. Questions are ranked on 5- to 7-point Likert scales, with higher scores indicating better health status.

  5. Change in patient-reported health when on beta-blocker versus when off beta-blocker, as measured by the EuroQol-5D Visual Analogue System (EQ-5D VAS) [ Time Frame: Baseline, Week 6, Week 12, Week 18, Week 24 ]
    The EuroQol-5D Visual Analogue System (EQ-5D VAS) indicates patient-perceived health on a vertical visual analogue scale. The scale ranges from 0, indicating poorest health, to 100, indicating best health.



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): NCT04767061


Locations
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United States, New York
Weill Cornell Medicine
New York, New York, United States, 10021
Sponsors and Collaborators
Weill Medical College of Cornell University
The New York Community Trust
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: NCT04767061    
Other Study ID Numbers: 19-10020922-02
P19-000458 ( Other Grant/Funding Number: New York Community Trust )
First Posted: February 23, 2021    Key Record Dates
Last Update Posted: June 24, 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
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