Clinical trial NCT05585125: A Preliminary Study for INFORMED
Official title: A Preliminary Study for the Intervention of an N-of-1 Protocol For Medication Optimization
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: 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
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2022-10-18
Enrollment: 20
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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).

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: Change in participant's confidence regarding their preference to continue or discontinue beta-blocker, as assessed by qualitative interviews
timeFrame: From the date of their baseline visit to the date of their last follow-up interview, assessed up to 88 weeks.
measure: Change in participant decision-confidence, as measured by the Decisional Conflict Scale (DCS)
timeFrame: From the date of their baseline visit, to the date of their end of intervention visit, assessed up to 36 weeks.
Secondary outcomes:
measure: Features of a feasible and pragmatic protocol for deprescribing N-of-1 trials in participants with Heart Failure with Preserved Ejection Fraction, as measured by qualitative interviews.
timeFrame: From the date of their baseline visit to the date of their last follow-up interview, assessed up to 88 weeks.
measure: Change in participants feeling informed through an N-of-1 protocol, as measured by the Decisional Conflict sub-scale
timeFrame: From the date of their baseline visit, to the date of their end of intervention visit, assessed up to 36 weeks.
measure: Change in participants feeling uncertainty through an N-of-1 protocol, as measured by the Decisional Conflict sub-scale
timeFrame: From the date of their baseline visit, to the date of their end of intervention visit, assessed up to 36 weeks.
measure: Change in participants feeling supported through an N-of-1 protocol, as measured by the Decisional Conflict sub-scale
timeFrame: From the date of their baseline visit, to the date of their end of intervention visit, assessed up to 36 weeks.
measure: Change in participants decision effectiveness through an N-of-1 protocol, as measured by the Decisional Conflict sub-scale
timeFrame: From the date of their baseline visit, to the date of their end of intervention visit, assessed up to 36 weeks.
measure: Change in shared decision making through an N-of-1 protocol, as measured by the 9-item Shared Decision-Making Questionnaire
timeFrame: From the date of their baseline visit, to the date of their end of intervention visit, assessed up to 36 weeks.
measure: Change in participant activation through an N-of-1 protocol, as assessed by the Patient Activation Measure (PAM)
timeFrame: From the date of their baseline visit, to the date of their end of intervention visit, assessed up to 36 weeks.
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: