Trial Outcomes & Findings for Pilot Deprescribing N-of-1 Trials for Beta-blockers in HFpEF (NCT NCT04757584)

NCT ID: NCT04757584

Last Updated: 2024-04-09

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

9 participants

Primary outcome timeframe

Baseline

Results posted on

2024-04-09

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.
On or Off Beta Blockers Up to 6 Wks STARTED	5	4
On or Off Beta Blockers Up to 6 Wks COMPLETED	5	4
On or Off Beta Blockers Up to 6 Wks NOT COMPLETED	0	0
Down-titration/Up-titration Up to 6 Wks STARTED	5	4
Down-titration/Up-titration Up to 6 Wks COMPLETED	5	4
Down-titration/Up-titration Up to 6 Wks NOT COMPLETED	0	0
Up-titration/Down-titration Up to 6 Wks STARTED	0	2
Up-titration/Down-titration Up to 6 Wks COMPLETED	0	2
Up-titration/Down-titration Up to 6 Wks NOT COMPLETED	0	0
Down-titration/Up-Titration Up to 6 Wks STARTED	0	0
Down-titration/Up-Titration Up to 6 Wks COMPLETED	0	0
Down-titration/Up-Titration Up to 6 Wks NOT COMPLETED	0	0
Follow-up STARTED	5	4
Follow-up COMPLETED	5	4
Follow-up NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pilot Deprescribing N-of-1 Trials for Beta-blockers in HFpEF

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Baseline

Outcome measures

Outcome measures
Measure	Beta Blocker ABAB Sequence n=5 Participants 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.	Beta Blocker BABA Sequence n=4 Participants 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.
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	3 participants
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	3 participants
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	3 participants
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	2 participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Beta Blocker ABAB Sequence n=5 Participants 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.	Beta Blocker BABA Sequence n=4 Participants 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.
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	4 Participants
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	3 Participants
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	2 Participants

Adverse Events

Beta Blocker ABAB Sequence

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Beta Blocker BABA Sequence

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Maryam Hyder

Weill Cornell Medicine

Phone: 646-962-5904

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Beta Blocker ABAB Sequence n=5 Participants 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.	Beta Blocker BABA Sequence n=4 Participants 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.	Total n=9 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants