A Preliminary Study for INFORMED

Phase 4Enrolling By InvitationNCT05585125

Weill Medical College of Cornell University20 enrolled

Overview

Investigators will determine whether N-of-1 trials, as a pragmatic, participant-centered approach to medication optimization that can overcome key barriers of deprescribing, can lead to increased participant confidence regarding their preference to continue or discontinue beta-blockers in older adults with Heart Failure with Preserved Ejection Fraction (HFpEF).

This is an unblinded NIH Stage I of Behavioral Intervention Development trial, using serial multiple-period single participant crossover design. Investigators will enroll 20 participants, conducting an N-of-1 trial in each. The intervention is a two-arm crossover withdrawal/reversal design (On \[A\] vs. Off \[B\]) with up to 6 periods, each period lasting up to 6 weeks. The sequence of treatment will be randomized to either ABAB or BABA. Each participant will have the option to participate in additional (no more than 6) periods if they wish to gather more data. The intervention drug will be beta-blockers, previously prescribed to the participants by their physician. The investigators have developed a titration algorithm, where during the On period (A), participants will be on their baseline beta-blocker dose (or the highest dose they can safely tolerate). During the Off period (B), their beta-blockers will be down-titrated and subsequently discontinued (or at the lowest dose they can safely tolerate); we will decrease the dose of the beta-blocker by 50% every week regardless of which beta-blocker they are on. When returning to On, from Off, we will up-titrate by 50% until reaching their home dose (or the highest dose they can safely tolerate).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

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

Interventions

Beta blockerDRUG

The intervention is a two-arm crossover withdrawal/reversal design (On \[A\] vs Off \[B\]) with up to 6 periods, each period lasting up to 6 weeks. During the On period (A), participants will be on their home beta-blocker (or highest tolerable) dose. During the Off period (B), their beta blockers will be down-titrated and subsequently discontinued (or the lowest tolerable dose). Participants will be randomized into either ABAB or BABA sequences. Other names: acebutolol, atenolol, betaxolol, bisoprolol, carvedilol, labetalol, metoprolol, metoprolol succinate, metoprolol tartrate, nadolol, nebivolol, propranolol, penbutolol, pindolol, propranolol

Beta blockerDRUG

Eligibility

Sex: ALLMin age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Ambulatory adults age ≥ 65 years with HFpEF, according to ACC/AHA guidelines (signs and symptoms of heart failure AND ejection fraction ≥ 50%) 2. Taking beta-blocker Exclusion Criteria: 1. Alternate cause(s) of HFpEF Syndrome: 1. Severe aortic stenosis 2. Moderate-severe mitral stenosis 3. Constrictive pericarditis 4. High output HF 5. Infiltrative cardiomyopathy 2. Other compelling indication(s) for beta-blocker 1. Prior EF \< 50% 2. Hypertrophic cardiomyopathy 3. Angina 4. Acute coronary syndrome, myocardial infarction, or coronary artery bypass surgery in prior 3 years 5. History of ventricular tachycardia/arrhythmia 6. Atrial arrhythmia with hospitalization for rapid ventricular response, prior 1 year 7. Heart rate \>100 bpm within the prior 3 months 8. Atrial arrhythmia with ventricular rate \>90 per minute in the prior 3 months 9. Systolic blood pressure readings \>160 mmHg within the prior 3 months, unless classified as white coat hypertension/effect (and home blood pressures below 140 mmHg) 10. Non-cardiac indications (e.g., migraine prevention, anxiety symptom management, hyperthyroidism, essential tumor reduction) 3. Clinical instability (N-of-1 trials are appropriate for stable conditions only) 1. Decompensated heart failure 2. Hospitalization in the past 30 days 3. Medication changes or procedures in the prior 14 days that could confound observations/data at PI discretion 4. Anticipated medication changes or procedures in subsequent 3 months that could confound observations/data at PI discretion 5. Clinical instability from other medical issues 4. Estimated life expectancy \< 6 months 5. Moderate-severe dementia or psychiatric disorder precluding informed consent 6. Language barrier that will preclude informed consent and ability to comprehend study procedures 7. Non-compliance or inability to complete study procedures 8. Enrollment in a clinical trial not approved for co-enrollment 9. Any condition that, in the Principal Investigator or treating physician's opinion, makes the patient unsuitable for study participation

Locations (1)

Weill Cornell Medicine

New York, New York, United States

Outcomes

Primary Outcomes

Change in participant's confidence regarding their preference to continue or discontinue beta-blocker, as assessed by qualitative interviews

Qualitative interviews will be conducted to assess the change in confidence through their experience participating in N-of-1 trials. Directed content analysis methods will be used to develop relevant categories and themes from interview transcript data. Transcripts will be coded and analyzed by two team members, consulting additional members to establish consensus where needed. Inter-rater reliability between coders will be established using Cohen's Kappa score.

Time frame: From the date of their baseline visit to the date of their last follow-up interview, assessed up to 88 weeks.

Change in participant decision-confidence, as measured by the Decisional Conflict Scale (DCS)

Measures participant perceptions of uncertainty in decision-making, factors contributing to uncertainty, and effective decision-making. A set of 16 questions with responses ranging from "strongly agree" = (0) to "strongly disagree" = (4). Scores are summed together to produce an overall score between 0 and 100. Lower scores indicate feeling informed and low decisional conflict whereas higher scores indicate feelings of uncertainty and high decisional conflict.

Time frame: From the date of their baseline visit, to the date of their end of intervention visit, assessed up to 36 weeks.

Secondary Outcomes

Features of a feasible and pragmatic protocol for deprescribing N-of-1 trials in participants with Heart Failure with Preserved Ejection Fraction, as measured by qualitative interviews.

Qualitative interviews will be conducted to assess the feasibility and acceptability of participant-facing materials and themes related to N-of-1 trials, and their experience participating in them, at each of the following time points. Directed content analysis methods will be used to develop relevant categories and themes from interview transcript data. Transcripts will be coded and analyzed by two team members, consulting additional members to establish consensus where needed. Inter-rater reliability between coders will be established using Cohen's Kappa score.

Data from ClinicalTrials.gov

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