N-of-1 for Beta-Blockers in Cardiac Amyloidosis

Weill Cornell Medicine (WCM)

Status and phase: Invitation-only; Phase 4

Conditions: Cardiac Amyloidosis; TTR Cardiac Amyloidosis; Heart Diseases

Treatments: Drug: Beta blocker

Study type: Interventional

Funder types: Other

Identifiers

NCT05019027

21-07023710

Details and patient eligibility

About

The study team will generate preliminary data on whether patients with cardiac amyloidosis feel better when their beta-blocker is stopped. To achieve this objective, 20 N-of-1 trials (on vs. off) will be conducted, and the study team will subsequently interview participants to better understand their outcomes. Each subject will participate in 2 periods lasting between up to 6 weeks each based on each patient's health profile. We will also engage stakeholders to understand the acceptability and feasibility of deprescribing N-of-1 trials. The N-of-1 trials will be iteratively refined in real-time based on feedback.

Full description

The intervention is an unblinded NIH Stage I of Behavioral Intervention Development trial, using a single-arm crossover withdrawal/reversal design (On [A] vs. Off [B]) with 2 periods, each period lasting up to 6 weeks, allowing for down-titration and washout. During the On (A) period, participants will be on their beta-blocker (or the highest dose they can safely tolerate), as previously prescribed to the subjects by their physician. During the Off (B) period, 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 beta-blocker by 50% every week regardless of which beta-blocker they are on, similar to an algorithm used in a prior deprescribing trial.

Enrollment: 20 estimated patients

Sex: All

Ages: 65+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Ambulatory adults age ≥65 years with TTR-cardiac amyloidosis (confirmed by PYP scan or biopsy)
2. Taking beta-blocker

Exclusion criteria

1. Other compelling indication(s) for beta-blockers:

   1. Angina
   2. Acute coronary syndrome, myocardial infarction or coronary artery bypass surgery in prior 3 years
   3. Atrial arrhythmia with hospitalization for rapid ventricular response, prior 1 year
   4. Heart rate >100 bpm within the prior 3 months
   5. Atrial arrhythmia with ventricular rate >90 beats per minute within the prior 3 months
   6. Systolic blood pressure readings >160 mmHg within the prior 1 month, unless classified as white coat hypertension/effect (e.g., migraine prevention, anxiety symptom management, hyperthyroidism, essential tumor reduction)

2. Clinical instability (N-of-1 trials are appropriate for stable conditions only)

   1. Decompensated heart failure
   2. Hospitalized in the past 30 days
   3. Medication changes or procedures in the prior 14 days that could confound observations/data at Principal Investigator 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

3. Estimated life expectancy <6 months

4. Moderate-severe dementia or psychiatric disorder precluding informed consent

5. Language barrier that will preclude informed consent and ability to comprehend study procedures

6. Non-compliance or inability to complete study procedures

7. Enrollment in a clinical trial not approved for co-enrollment

8. Any condition that, in Principal Investigator or treating physician's opinion, makes the patient unsuitable for study participation

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

On-Off Sequence

Other group

Description:

This arm will follow an On-Off sequence. This is the only arm in the study. Subjects will begin in the On phase (Period 1), where they will be on their beta-blocker (or the highest dose they can safely tolerate) as previously prescribed to the subjects by their physician. Subjects will then continue to the Off phase (Period 2) where they will down-titrate their beta-blocker by 50% each week until they are completely off the drug (or the lowest dose they can safely tolerate) for a total of two weeks. At the end of Period 2, the subjects will have their End of Intervention visit to determine if they would like to continue or discontinue their beta-blockers for the foreseeable future.

Treatment:

Drug: Beta blocker