Clinical trial

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

Name

19-10020922-02

Description

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.

Trial arms

Trial start

2021-04-01

Estimated PCD

2022-04-28

Trial end

2023-04-28

Status

Completed

Phase

Early phase I

Treatment

Beta blockers

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.

Arms:

Beta Blocker ABAB Sequence, Beta Blocker BABA Sequence

Other names:

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

Size

Primary endpoint

Change in Physical Activity When on Beta-blocker Versus When Off Beta-blocker, as Measured by Step Count on Wearable Activity Monitoring Device

The maximum amount of time a subject could have been assessed for this outcome measure is 8-weeks (last 2 weeks of each period for up to 4 periods).

Change in Lower Extremity Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by the Balance Portion of a Modified Version of the Short Physical Performance Battery.

The maximum amount of time a subject could have been assessed for this outcome measure is 24-weeks. This outcome was measured at baseline and at each end of period visit.

Change in Lower Extremity Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by the Gait Speed Portion of a Modified Version of the Short Physical Performance Battery.

The maximum amount of time a subject could have been assessed for this outcome measure is 24-weeks. This outcome was measured at baseline and at each end of period visit.

Change in Lower Extremity Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by the Chair Rise Portion of a Modified Version of the Short Physical Performance Battery.

The maximum amount of time a subject could have been assessed for this outcome measure is 24-weeks. This outcome was measured at baseline and at each end of period visit.

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)

The maximum amount of time a subject could have been assessed for this outcome measure is 6-weeks. This outcome was measured at the end of the first and second visit.

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: 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

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'CROSSOVER', 'primaryPurpose': 'OTHER', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 9, 'type': 'ACTUAL'}}

Updated at

2023-09-08

1 organization

1 drug

5 indications

Organization

Weill Medical College of Cornell University

Drug

Beta blockers

Indication

Congestive Heart Failure

Indication

diastolic

Indication

Heart Failure with Preserved Ejection Fraction

Indication

Heart Failure

Indication

Heart disease