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A Preliminary Study for INFORMED (PRE-INFORMED)

Primary Purpose

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

Status

Recruiting

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Beta blocker

About this trial

This is an interventional other trial for Heart Failure focused on measuring 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

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

Alternate causes of HFpEF Syndrome:
1. Severe aortic stenosis
2. Moderate-severe mitral stenosis
3. Constrictive pericarditis
4. High output HF
5. 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 years
5. History of ventricular tachycardia
6. Atrial arrhythmia with hospitalization for rapid ventricular response, prior 1 year
7. Sinus tachycardia > 100 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 heart failure
2. Hospitalization in past 30 days
3. Medication changes or procedures in prior 14 days that could confound observations/data, at PI discretion
Estimated life expectancy < 6 months
Moderate-severe dementia or psychiatric disorder precluding informed consent
Any condition that, in the Principal Investigator's opinion, makes the patient unsuitable for study participation

Sites / Locations

Weill Cornell MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Beta Blocker ABAB Sequence

Beta Blocker BABA Sequence

Arm Description

This arm will follow an ABAB sequence. "A" representing ON beta blockers and "B" representing OFF beta blockers. Participants 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, participants will restart beta-blockers, gradually up-titrating until reaching their home dose and finally during period 4, the investigators will again conduct a dose reduction until they are off of beta-blockers. If the subject chooses to continue into Period 5 the investigators will repeat the same up-titration process until the participant reaches their home dose, and finally during Period 6, the dose will be reduced until the participant is off of their beta-blocker.

This arm will follow a BABA sequence. "A" representing ON beta blockers and "B" representing OFF beta blockers. Participants 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 up-titration will begin until they are back on their previously prescribed dose of beta blockers. During Period 3, the investigators will again conduct a dose reduction, until the participant is off of beta blockers and finally during Period 4, the investigators will up-titrate them back to their home dose of beta blockers. If the participant chooses to continue into Period 5 the investigators will repeat the same down-titration process until the participant is off their beta-blocker, and finally during Period 6, the dose will be increased until the participant is back to their home dose.

Outcomes

Primary Outcome Measures

Change in patient's confidence regarding the decision to continue or discontinue beta-blocker, as assessed by qualitative interviews

Change in patient 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.

Secondary Outcome Measures

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

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

A set of 3 items within the Decisional Conflict Scale assessing participant's sense of knowing the options available to them and their benefits. Answers range from "strongly agree" = (0) to "strongly disagree" = (4). Scores are summed together to produce an overall score between 0 (feels extremely informed) and 100 (feels extremely uninformed).

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

A set of 3 items within the Decisional Conflict Scale assessing how sure participants feel about making a given decision. Answers range from "strongly agree" = (0) to "strongly disagree" = (4). Scores are summed together to produce an overall score between 0 (feels extremely certain about best choice) and 100 (feels extremely uncertain about best choice).

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

A set of 3 items within the Decisional Conflict Scale assessing if participant's feel supported or pressured by others when making a given decision. Answers range from "strongly agree" = (0) to "strongly disagree" = (4). Scores are summed together to produce an overall score between 0 (feels extremely supported in decision making) and 100 (feels extremely unsupported in decision making).

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

A set of 4 items within the Decisional Conflict Scale assessing if participants feel satisfied and informed in their decision making. Answers range from "strongly agree" = (0) to "strongly disagree" = (4). Scores are summed together to produce an overall score between 0 (good decision) and 100 (bad decision).

Change in shared decision making through an N-of-1 protocol, as measured by the 9-item Shared Decision-Making Questionnaire

Measures patients' feeling of inclusion during the decision-making process of their treatment options. The 9-item questionnaire asks participants to respond to statements with answers to the questions ranging from "completely disagree" to "completely agree". Responses range from (0) = "completely disagree" to (5) = "completely agree" and are scored on a six-point Likert scale. Scores are summed together to produce an overall score between 0 (low involvement and 45 (high involvement).

Change in patient activation through an N-of-1 protocol, as assessed by the Patient Activation Measure (PAM)

Assesses an individual's knowledge, skills and confidence integral to managing one's own health and healthcare. Participants respond to a set of statements with answers ranging from "disagree strongly," "disagree," "agree," "strongly agree," and "not applicable." The responses are quantified to produce a score ranging from 0 to 100, and respondents fall into one of four levels of patient activation: Disengaged & Overwhelmed, Becoming Aware but still Struggling, Taking Action & Gaining Control, and Maintaining Behaviors & Pushing Further. A score of 0 (Disengaged & Overwhelmed) indicates low patient activation, patient is passive with low healthcare knowledge and adherence. A score of 100 (Maintaining Behaviors & Pushing Further) indicates high patient activation, with active maintenance of a healthy lifestyle.

Full Information

NCT ID

NCT05585125

First Posted

October 11, 2022

Last Updated

September 22, 2023

Sponsor

Weill Medical College of Cornell University

Collaborators

National Institute on Aging (NIA)

1. Study Identification

Unique Protocol Identification Number

NCT05585125

Brief Title

A Preliminary Study for INFORMED

Acronym

PRE-INFORMED

Official Title

A Preliminary Study for the Intervention of an N-of-1 Protocol For Medication Optimization

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 2023 (Anticipated)

Primary Completion Date

April 2026 (Anticipated)

Study Completion Date

April 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Weill Medical College of Cornell University

Collaborators

National Institute on Aging (NIA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

Detailed Description

This is an unblinded NIH Stage I of Behavioral Intervention Development trial, using serial multiple-period single patient crossover design. Investigators will enroll 20 participants, conducting an N-of-1 trial in each of them. 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 periods if they wish to gather more data. The intervention drug will be beta-blockers, previously prescribed to the subjects by their physician. The investigators have developed a titration algorithm, where the participant's dose of beta-blocker will be decreased by 50% every week prior to their Off [B] period. Similarly, investigators will increase participant's beta-blocker dose by 50% every week prior to their On [A] period.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Other

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Beta Blocker ABAB Sequence

Arm Type

Active Comparator

Arm Description

Arm Title

Beta Blocker BABA Sequence

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Beta blocker

Other Intervention Name(s)

ABAB

Intervention Description

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), 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

Intervention Type

Drug

Intervention Name(s)

Beta blocker

Other Intervention Name(s)

BABA

Intervention Description

Primary Outcome Measure Information:

Title

Change in patient's confidence regarding the decision to continue or discontinue beta-blocker, as assessed by qualitative interviews

Time Frame

Baseline, End of each period (approx. weeks 6, 12, 18, and 24), month 6 follow-up, month 9 follow-up, and month 12 follow-up

Title

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

Description

Time Frame

Baseline and End of Intervention (approx. week 12, 18, or 24)

Secondary Outcome Measure Information:

Title

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

Time Frame

Baseline

Title

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

Time Frame

End of Period 1 (approx. week 6)

Title

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

Time Frame

End of Period 2 (approx. week 12)

Title

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

Time Frame

End of Period 3 (approx. week 18)

Title

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

Time Frame

End of Intervention (approx. week 24)

Title

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

Time Frame

Month 6 follow-up

Title

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

Time Frame

Month 9 follow-up

Title

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

Time Frame

Month 12 follow-up

Title

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

Description

Time Frame

Baseline and End of Intervention (approx. week 24)

Title

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

Description

Time Frame

Baseline and End of Intervention (approx. week 24)

Title

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

Description

Time Frame

Baseline and End of Intervention (approx. week 24)

Title

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

Description

Time Frame

Baseline and End of Intervention (approx. week 24)

Title

Change in shared decision making through an N-of-1 protocol, as measured by the 9-item Shared Decision-Making Questionnaire

Description

Time Frame

Baseline and End of Intervention (approx. week 24)

Title

Change in patient activation through an N-of-1 protocol, as assessed by the Patient Activation Measure (PAM)

Description

Time Frame

Baseline and End of Intervention (approx. week 24)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: Alternate causes of HFpEF Syndrome: Severe aortic stenosis Moderate-severe mitral stenosis Constrictive pericarditis High output HF Infiltrative cardiomyopathy Other compelling indication for beta-blocker Prior EF < 50% Hypertrophic cardiomyopathy Angina symptoms Acute coronary syndrome, myocardial infarction, or coronary artery bypass surgery in prior 3 years History of ventricular tachycardia Atrial arrhythmia with hospitalization for rapid ventricular response, prior 1 year Sinus tachycardia > 100 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) Decompensated heart failure Hospitalization in past 30 days Medication changes or procedures in prior 14 days that could confound observations/data, at PI discretion Estimated life expectancy < 6 months Moderate-severe dementia or psychiatric disorder precluding informed consent Any condition that, in the Principal Investigator's opinion, makes the patient unsuitable for study participation

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Princess Osma, BA

Phone

646-962-5910

pro4001@med.cornell.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Parag Goyal, MD, MSc

pag9051@med.cornell.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Parag Goyal, MD, MSc

Organizational Affiliation

Weill Medical College of Cornell University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Weill Cornell Medicine

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Princess Osma, BA

pro4001@med.cornell.edu

First Name & Middle Initial & Last Name & Degree

Parag Goyal, MD, MSc

12. IPD Sharing Statement

Plan to Share IPD

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A Preliminary Study for INFORMED

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