A Preliminary Study for INFORMED

Heart Failure Clinical Trial

— PRE-INFORMED  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05585125
• Other study ID #: 23-03025862 frmrly 22-08025181
• Secondary ID: 5K76AG064428-03f
• Status: Recruiting
• Phase: Phase 4
• Start date: February 7, 2024
• Est. completion date: July 2026

Study information

• Verified date: March 2024
• Source: Weill Medical College of Cornell University
• Contact: Princess Osma, BA
• Phone: 646-962-5910
• Email: pro4001[@]med.cornell.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: July 2026
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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 causes 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 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/arrhythmia

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

3. 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

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Beta blocker
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 AB or BA sequences. Other names: acebutolol, atenolol, betaxolol, bisoprolol, carvedilol, labetalol, metoprolol, metoprolol succinate, metoprolol tartrate, nadolol, nebivolol, propranolol, penbutolol, pindolol, propranolol, sotalol
• Beta blocker
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 AB or BA sequences. Other names: acebutolol, atenolol, betaxolol, bisoprolol, carvedilol, labetalol, metoprolol, metoprolol succinate, metoprolol tartrate, nadolol, nebivolol, propranolol, penbutolol, pindolol, propranolol, sotalol

Locations

Country	Name	City	State
United States	Weill Cornell Medicine	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in patient'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.
Primary	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.	From the date of their baseline visit, to the date of their end of intervention visit, assessed up to 36 weeks.
Secondary	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.	Qualitative interviews will be conducted to assess the feasibility and acceptability of subject-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.	From the date of their baseline visit to the date of their last follow-up interview, assessed up to 88 weeks.
Secondary	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).	From the date of their baseline visit, to the date of their end of intervention visit, assessed up to 36 weeks.
Secondary	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).	From the date of their baseline visit, to the date of their end of intervention visit, assessed up to 36 weeks.
Secondary	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).	From the date of their baseline visit, to the date of their end of intervention visit, assessed up to 36 weeks.
Secondary	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).	From the date of their baseline visit, to the date of their end of intervention visit, assessed up to 36 weeks.
Secondary	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).	From the date of their baseline visit, to the date of their end of intervention visit, assessed up to 36 weeks.
Secondary	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.	From the date of their baseline visit, to the date of their end of intervention visit, assessed up to 36 weeks.