Clinical trial NCT05019027: N-of-1 for Beta-Blockers in Cardiac Amyloidosis
Official title: N-of-1 Trials to Promote Deprescribing in Older Adults With Transthyretin Cardiac Amyloidosis
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE4
Conditions: Cardiac Amyloidosis
Heart Diseases
TTR Cardiac Amyloidosis
Keywords: beta blocker
cardiac amyloidosis
HFpEF
deprescribing
heart failure
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: U.S. Deprescribing Research Network
First posted: 2021-08-24
Enrollment: 20
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: The change in exercise capacity when on beta-blocker versus when off beta-blocker, as measured by peak oxygen consumption (VO2) during Cardiopulmonary Exercise Test (CPET).
timeFrame: End of Period 1 (Week 2, 3, 4, 5, or 6) and Period 2 (Week 8, 9, 10, 11, or 12)
measure: The change in patient-reported health status when on beta-blocker versus when off beta-blocker, as measured by Kansas City Cardiomyopathy Questionnaire (KCCQ-12).
timeFrame: Baseline, End of Period 1 (Week 2, 3, 4, 5, or 6), End of Period 2 (Week 8, 9, 10, 11, or 12)
measure: The change in patient-reported quality of life when on beta-blocker versus when off beta-blocker, as measured by the EuroQol-5d Visual Analogue Scale.
timeFrame: Baseline; End Period 1 (Weeks 2, 3, 4, 5, or 6), End of Period 2 (Weeks 8, 9, 10, 11, or 12)
Secondary outcomes:
measure: Change in patient-reported quality of life when on beta-blocker, as measured by the Patient-Reported Outcome Measurement Information System-29 (PROMIS-29)
timeFrame: Baseline; Weekly for up to 12 weeks; End of Period 1 (Week 2, 3, 4, 5, or 6), Period 2 (Week 8, 9, 10, 11, or 12)
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Parag Goyal, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: