Heart Failure, Heart Failure, Diastolic, Heart Failure With Preserved Ejection Fraction, Cardiac Failure, Heart Disease
Conditions
Brief summary
In this study, we will test the feasibility of N-of-1 trials for deprescribing beta-blockers in patients with Heart Failure with Preserved Ejection Fraction. To achieve this objective we will conduct 16 4-period N-of-1 trials (on vs. off) and subsequently interview participants to better understand feasibility and pragmatism. The N-of-1 trials will be iteratively refined in real-time based on this feedback.
Interventions
DRUGBeta blockers
The intervention is a two-arm crossover withdrawal/ reversal design (On \[A\] vs Off \[B\]) with up to 4 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 ABAB or BABA sequences.
Sponsors
National Institute on Aging (NIA)
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ambulatory adults ≥65 years of age with Heart Failure with Preserved Ejection Fraction (HFpEF) according to ACC/AHA guidelines: (signs and symptoms of Heart failure \[HF\] and ejection fraction \[EF\] ≥50%) * Taking Beta blocker
Exclusion criteria
* Alternate Causes of HFpEF Syndrome: 1. Severe valvular disease 2. Constrictive pericarditis 3. High output heart failure 4. Infiltrative cardiomyopathy * 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 year 5. History of ventricular tachycardia 6. Atrial arrhythmia with hospitalization for rapid ventricular response, prior 1 year 7. Sinus tachycardia \> 100 beats per minute (bpm), atrial arrhythmia with ventricular rate \>90 bpm, systolic blood pressure \> 160 mmHg * Clinical instability (N-of-1 trials are appropriate for stable conditions only) 1. Decompensated HF 2. Hospitalized in past 30 days 3. Medication changes or procedures in prior 14 days (to prevent confounding from other interventions), at PI discretion * Estimated life expectancy \<6 months * Moderate-severe dementia or psychiatric disorder precluding informed consent * Any condition that, in Principal Investigator's opinion, makes the patient unsuitable for study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 Interview | Baseline | Qualitative interviews were conducted to assess the feasibility and acceptability of deprescribing N-of-1 trials and participant experiences. Directed content analysis methods were used to develop relevant categories and themes from interview transcript data. Transcripts were coded and analyzed by two team members, consulting additional members to establish consensus where needed. Inter-rater reliability between coders was established. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Beta Blocker ABAB Sequence This arm will follow an ABAB sequence. A representing ON beta blockers and B representing OFF beta blockers. Subjects in this arm will continue their home dose during the initial A period, they will then crossover into Period 2, where dose reduction will begin until they are off of beta blockers. After Period 2, the subjects have the option to decide if they want to be on or off their beta blocker and proceed with the Follow-Up Phase, or continue to Period 3 if they don't feel ready to make that decision to stay on or go off their beta blocker yet. During Period 3, they will restart beta-blockers, gradually up-titrating until reaching their home dose. Finally, during Period 4, we will again conduct a dose reduction until off of beta blockers.
Beta blockers: The intervention is a two-arm crossover withdrawal/ reversal design (On \[A\] vs Off \[B\]) with up to 4 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 ABAB or BABA sequences. | 5 |
| Beta Blocker BABA Sequence This arm will follow a BABA sequence. A representing ON beta blockers and B representing OFF of beta blockers. Subjects in this arm will have their previously prescribed beta blocker dose reduced until they are completely off of beta blockers during Period 1. They will then crossover into Period 2, where uptitration will begin until they are back on their previously prescribed dose of beta blockers. After Period 2, the subjects have the option to decide if they want to be on or off their beta blocker and proceed with the Follow-Up Phase, or continue to Period 3 if they don't feel ready to make that decision to stay on or go off their beta blocker yet. During Period 3, we will again conduct a dose reduction, until the subject is off of beta blockers. Finally, during Period 4, we will up-titrate them back to their home dose of beta blockers.
Beta blockers: The intervention is a two-arm crossover withdrawal/ reversal design (On \[A\] vs Off \[B\]) with up to 4 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 ABAB or BABA sequences. | 4 |
| Total | 9 |
Baseline characteristics
| Characteristic | Beta Blocker ABAB Sequence | Beta Blocker BABA Sequence | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 4 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 4 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 4 Participants | 9 Participants |
| Region of Enrollment United States | 5 participants | 4 participants | 9 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
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 Interview
Qualitative interviews were conducted to assess the feasibility and acceptability of deprescribing N-of-1 trials and participant experiences. Directed content analysis methods were used to develop relevant categories and themes from interview transcript data. Transcripts were coded and analyzed by two team members, consulting additional members to establish consensus where needed. Inter-rater reliability between coders was established.
Time frame: Baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Beta Blocker ABAB Sequence | 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 Interview | Positive attitude towards deprescribing | 4 participants |
| Beta Blocker ABAB Sequence | 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 Interview | Questions/concerns about deprescribing N-of-1 trials | 2 participants |
| Beta Blocker ABAB Sequence | 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 Interview | Desire for patient-centered educational materials about deprescribing and N-of-1 trials | 4 participants |
| Beta Blocker ABAB Sequence | 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 Interview | Desire for short, pragmatic visits | 2 participants |
| Beta Blocker BABA Sequence | 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 Interview | Desire for short, pragmatic visits | 2 participants |
| Beta Blocker BABA Sequence | 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 Interview | Positive attitude towards deprescribing | 3 participants |
| Beta Blocker BABA Sequence | 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 Interview | Desire for patient-centered educational materials about deprescribing and N-of-1 trials | 3 participants |
| Beta Blocker BABA Sequence | 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 Interview | Questions/concerns about deprescribing N-of-1 trials | 3 participants |
Primary
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 Interview
Qualitative interviews were conducted to assess the feasibility and acceptability of deprescribing N-of-1 trials and participant experiences. Directed content analysis methods were used to develop relevant categories and themes from interview transcript data. Transcripts were coded and analyzed by two team members, consulting additional members to establish consensus where needed. Inter-rater reliability between coders was established. The outcome measure data is the cumulative count of subjects who identified categories and themes from interview transcript data collected during the span of the outcome measure time frame, up to 6 times over 36 weeks.
Time frame: The maximum amount of time a subject could have been assessed for this outcome measure is 6 times across 36 weeks. This outcome was measured at each end of period visit (weeks 6, 12, 18, 24, 30) and at the end of intervention (weeks 12, 18, 24, 30, or 36)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Beta Blocker ABAB Sequence | 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 Interview | Technologic challenges related to the protocol | 5 Participants |
| Beta Blocker ABAB Sequence | 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 Interview | Desire for study contact that balances safety and pragmatism | 5 Participants |
| Beta Blocker ABAB Sequence | 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 Interview | Feedback on data visualization tool | 5 Participants |
| Beta Blocker BABA Sequence | 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 Interview | Technologic challenges related to the protocol | 4 Participants |
| Beta Blocker BABA Sequence | 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 Interview | Desire for study contact that balances safety and pragmatism | 3 Participants |
| Beta Blocker BABA Sequence | 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 Interview | Feedback on data visualization tool | 2 Participants |