A Preliminary Study for INFORMED (PRE-INFORMED)

Weill Cornell Medicine (WCM)

Status and phase: Enrolling; Phase 4

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

Treatments: Drug: Beta blocker

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05585125

23-03025862 frmrly 22-08025181

formerly 22-08025181 (Other Identifier)

5K76AG064428-03 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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).

Full description

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).

Enrollment: 20 estimated patients

Sex: All

Ages: 65+ years old

Volunteers: No Healthy Volunteers

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 (and home blood pressures below 140 mmHg)
   10. Non-cardiac indications (e.g., migraine prevention, anxiety symptom management, glaucoma, 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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

Beta-Blocker ABAB Sequence

Active Comparator group

Description:

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.

Treatment:

Drug: Beta blocker

Drug: Beta blocker

Beta-Blocker BABA Sequence

Active Comparator group

Description:

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.

Treatment:

Drug: Beta blocker

Drug: Beta blocker