A Preliminary Study for INFORMED

NCT05585125 | Enrolling By Invitation Phase 4 DMC FDA Drug

• 3 other identifiers: 23-03025862 frmrly 22-080251815K76AG064428-03formerly 22-08025181
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

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

Secondary Outcomes (7)

• 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.

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

• Change in participants feeling informed through an N-of-1 protocol, as measured by the Decisional Conflict sub-scale

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

• Change in participants feeling uncertainty through an N-of-1 protocol, as measured by the Decisional Conflict sub-scale

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

• Change in participants feeling supported through an N-of-1 protocol, as measured by the Decisional Conflict sub-scale

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

• Change in participants decision effectiveness through an N-of-1 protocol, as measured by the Decisional Conflict sub-scale

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

Study Arms (2)

Beta-Blocker ABAB Sequence

ACTIVE COMPARATOR

This arm will follow an ABAB sequence: ON beta-blockers (A) and OFF beta-blockers (B). Participants start with their home beta-blocker dose in Period 1 (A), and then switch to Period 2 (B), where the dose is slowly reduced until they are off their beta-blocker (or the lowest tolerable dose). Participants are then asked if they have enough information to clarify their preference about continuing or discontinuing their beta-blocker. Participants can choose to engage in 2-6 periods based on whether they need more information to make a preference. These extra phases follow the same ON-OFF pattern (ABABAB), meaning if the participant chooses to continue into Period 3 (A), the study team will restart the participant's beta-blocker, and slowly up-titrate until they reach their home dose, or their highest tolerable dose. This continues until the participant has enough information to clarify their preference about their beta-blocker, with a limit of 6 periods.

Drug: Beta blocker

Beta-Blocker BABA Sequence

ACTIVE COMPARATOR

This arm will follow a BABA sequence: OFF beta-blockers (B) and ON beta-blockers (A). Participants start Period 1 (B) by slowly reducing the participant's beta-blocker home dose by 50% each week until they are off (or the lowest tolerable dose), then switch to Period 2 (A), where they restart their beta-blocker and slowly up-titrate until they reach their home dose (or the highest tolerable dose). Participants are then asked if they have enough information to clarify their preference about continuing or discontinuing their beta-blocker. Participants can choose to engage in 2-6 periods based on whether they need more information. The extra phases follow the same OFF-ON pattern (BABABA), meaning if they choose to continue into Period 3 (B), the participant will slowly reduce their beta-blocker until they are off (or the lowest tolerable dose). This continues until the participant has enough information to clarify their preference about their beta-blocker, with a max of 6 periods.

Drug: Beta blocker

Interventions

Beta blocker DRUG

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

Also known as: ABAB

Beta-Blocker ABAB Sequence

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Ambulatory adults age ≥ 65 years with HFpEF, according to ACC/AHA guidelines (signs and symptoms of heart failure AND ejection fraction ≥ 50%)
• Taking beta-blocker

You may not qualify if:

• Alternate cause(s) of HFpEF Syndrome:
• Severe aortic stenosis
• Moderate-severe mitral stenosis
• Constrictive pericarditis
• High output HF
• Infiltrative cardiomyopathy
• Other compelling indication(s) for beta-blocker
• Prior EF \< 50%
• Hypertrophic cardiomyopathy
• Angina
• Acute coronary syndrome, myocardial infarction, or coronary artery bypass surgery in prior 3 years
• History of ventricular tachycardia/arrhythmia
• Atrial arrhythmia with hospitalization for rapid ventricular response, prior 1 year
• Heart rate \>100 bpm within the prior 3 months
• Atrial arrhythmia with ventricular rate \>90 per minute in the prior 3 months

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Weill Cornell Medicine

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Heart Failure; Heart Failure, Diastolic; Heart Diseases

Interventions

Adrenergic beta-Antagonists

Condition Hierarchy (Ancestors)

Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs

Study Officials

• Parag Goyal, MD, MSc

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2022
• First Posted: October 18, 2022
• Study Start: February 7, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: October 23, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)