Heart FailurePhase 4NCT04757584
Pilot Deprescribing N-of-1 Trials for Beta-blockers in HFpEF
A Phase 4 study testing Beta blockers in people with Heart Failure and Heart Failure, Diastolic, run by Weill Medical College of Cornell University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Heart Failure, Heart Failure, Diastolic, Heart Failure With Preserved Ejection Fraction
- What is being tested?
- Beta blockers
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2021to 28 Apr 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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
Who cannot join
- Alternate Causes of HFpEF Syndrome:
- Severe valvular disease
- Constrictive pericarditis
- High output heart failure
- Infiltrative cardiomyopathy
- Other compelling indication for beta blocker:
Show all 20Show fewer
- Prior EF < 50%
- Hypertrophic cardiomyopathy
- Angina symptoms
- Acute coronary syndrome, myocardial infarction or coronary artery bypass surgery in prior 3 year
- History of ventricular tachycardia
- Atrial arrhythmia with hospitalization for rapid ventricular response, prior 1 year
- 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)
- Decompensated HF
- Hospitalized in past 30 days
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: N-of-1 Trials for Deprescribing Beta-blockers in HFpEF
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.
- Conditions
- Heart Failure, Heart Failure, Diastolic, Heart Failure With Preserved Ejection Fraction, Cardiac Failure, Heart Disease
- Being tested
- Beta blockers
- Medical subject headings
- Heart Failure, Heart Failure, Diastolic, Heart Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Beta blockersDrug
Also called atenolol, betaxolol, bisoprolol, metoprolol
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.
| Study group | Role | What they receive |
|---|---|---|
| Beta Blocker ABAB Sequence | Active comparator | 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. Receives: Drug: Beta blockers |
| Beta Blocker BABA Sequence | Active comparator | 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. Receives: Drug: Beta blockers |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline
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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2021
- Study start1 Apr 2021
- Primary completion28 Apr 2023
- Study completion28 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Parag Goyal, MD, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04757584
- Sponsor's protocol ID
- 19-10020922-01
- Other IDs
- K76AG064428
- Status last verified
- Mar 2024
- First submitted
- 12 Feb 2021
- Last updated
- 9 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- N-of-1 Trials for Deprescribing Beta-blockers in HFpEF
- ClinicalTrials.gov ID
- NCT04757584
- Acronym / sponsor ID
- 19-10020922-01
- Conditions
- Heart Failure, Heart Failure, Diastolic, Heart Failure With Preserved Ejection Fraction, Cardiac Failure, Heart Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- 28 Apr 2023 (actual)
- Study completion
- 28 Apr 2023 (actual)
- First posted
- 17 Feb 2021 (actual)
- Results
- Posted 9 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Beta Blocker ABAB Sequence | Active comparator | Drug: Beta blockersThis 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 Blocker BABA Sequence | Active comparator | Drug: Beta blockersThis 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. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (20 listed)
- Alternate Causes of HFpEF Syndrome:
- Other compelling indication for beta blocker:
- Clinical instability (N-of-1 trials are appropriate for stable conditions only)
- Estimated life expectancy <6 months
- Moderate-severe dementia or psychiatric disorder precluding informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Beta blockersAlso: atenolol, betaxolol, bisoprolol, metoprololThe 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. | Drug | Beta Blocker ABAB Sequence, Beta Blocker BABA Sequence |
Primary outcome
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
Time frame: 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.
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
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)
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Parag Goyal, MD principal investigator
Weill Medical College of Cornell University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Beta blockers in people with Heart Failure and Heart Failure, Diastolic, run by Weill Medical College of Cornell University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2024.