Impact of Beta-blockers on Physical Function in HFpEF

• Sponsor: Weill Medical College of Cornell University (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04767061
• Collaborator: The New York Community Trust (Other)
• Enrollment: 16
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 29
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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

Study Design

• Study Type: Interventional
• Anticipated 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: Apr 1, 2021
• Anticipated Primary Completion Date: Dec 1, 2022
• Anticipated Study Completion Date: Sep 1, 2023

Arms and Interventions

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

Outcome Measures

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 [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 [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) [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) [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) [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) [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) [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) [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.

Eligibility Criteria

Criteria

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

• Principal Investigator: Parag Goyal, MD, Weill Medical College of Cornell University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT04767061
• Other Study ID Numbers: 19-10020922-02; P19-000458
• First Posted: Feb 23, 2021
• Last Update Posted: Jun 28, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Heart Failure; Heart Diseases; Heart Failure, Diastolic; Propranolol; Metoprolol; Atenolol; Sotalol; Nadolol; Acebutolol; Carvedilol; Nebivolol; Bisoprolol; Labetalol; Pindolol; Betaxolol; Penbutolol; Adrenergic beta-Antagonists

Study Results

No Results Posted as of Jun 28, 2022