N-of-1 Trial to Promote Beta-Blocker Titration in Heart Failure

N-of-1 Trials to Promote Patient-Centered Beta-Blocker Titration in Heart Failure With Reduced Ejection Fraction

In this study we seek to understand whether N-of-1 trials using a crossover withdrawal/reversal design with as many 2-week periods can be used to identify the highest tolerated beta-blocker dose for patients with Heart Failure with Reduced Ejection Fraction (HFrEF). To achieve this objective we will conduct a 2-arm randomized controlled trial of 50 participants, comparing intervention(N-of-1 trials) to enhanced usual care.

For participants randomized to the intervention, we will use collect data via validated patient-reported outcomes and then display this data on a visualization tool. This tool was iteratively developed for N-of-1 trials with patient input - a comparison of how the patient felt on different beta-blockers. If well-tolerated and the participant agrees to continue with dose escalation based on review of their data, the participant will take a higher dose for the next 2-week period; and the study team will again collect data on how they feel during this time. This approach of sharing end-of-period data with participants and subsequently escalating the dose (based on the participant's decision) for another 2-week period will continue until the guideline-directed target dose is reached or until the participant feels that their symptoms are limiting dose escalation. The N-of-1 intervention is purposefully structured to allow the participant to participate in as many periods (and as many dose combinations) as they wish until they are confident that they have reached their highest tolerated dose. This adaptive design for N-of-1 trials is intended to be patient-centered and patient-driven.

We will also conduct brief semi-structured interviews with intervention participants.

Participants randomized to enhanced usual care will not have access to patient-reported outcomes or the data visualization tool. Since attention can affect outcomes, we will "enhance usual care" by conducting phone calls at the same frequency as the intervention group.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure; Older Adults; Beta-blocker
• Intervention / Treatment: Behavioral: N-of-1 trials; Behavioral: Enhanced usual care

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Parag Goyal, MD, MSc; Phone Number: (646) 962-7571; Email: pag9051@med.cornell.edu
• Study Contact Backup: Name: Julie Lauffenburger, PharmD, PhD; Email: jlauffenubrger@bwh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged ≥60 years
• Diagnosed with HFrEF (LVEF <40%)
• Taking below 50% of guideline-based target β-blocker dose (guideline-based target doses: metoprolol 200mg daily; carvedilol 25mg BID; bisoprolol 10mg daily)

Exclusion Criteria:

• Contraindication to beta-blocker including allergy
• Treating physician disapproval of enrollment
• Clinical instability

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: N-of-1 Trials; N-of-1 trials using a crossover withdrawal/reversal design will allow for as many 2-week periods as needed to identify the highest tolerated beta-blocker dose	Behavioral: N-of-1 trials; N-of-1 trials using a crossover withdrawal/reversal design will allow for as many 2-week periods as needed to identify the highest tolerated beta-blocker dose
Active Comparator: Enhanced usual care; We will compare the intervention to an "enhanced usual care." Our study team will not provide guidance for dose titration (this will be at physician and patient discretion); and participants will not have access to PROs or the data visualization tool. Since attention can affect outcomes, we will "enhance usual care" by conducting phone calls at the same frequency as the intervention group.	Behavioral: Enhanced usual care; We will compare the intervention to an "enhanced usual care." Our study team will not provide guidance for dose titration (this will be at physician and patient discretion); and participants will not have access to PROs or the data visualization tool. Since attention can affect outcomes, we will "enhance usual care" by conducting phone calls at the same frequency as the intervention group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum beta-blocker dose achieved	Our primary endpoint is the maximum beta-blocker dose achieved, in proportion to target dose.	120 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants taking >50% of target dose	The secondary outcome will be the proportion of participants taking at least >50% of target beta-blocker dose.	120 days

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: National Institute on Aging (NIA); Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Estimated): May 5, 2026
• Primary Completion (Estimated): March 5, 2027
• Study Completion (Estimated): March 5, 2027

Study Registration Dates

• First Submitted: March 18, 2026
• First Submitted That Met QC Criteria: March 18, 2026
• First Posted (Actual): March 24, 2026

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Guideline-directed medical therapy; N-of-1 trials
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Health Care Quality, Access, and Evaluation; Investigative Techniques; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Epidemiologic Study Characteristics; Clinical Trials as Topic; Clinical Studies as Topic; Single-Case Studies as Topic
• Other Study ID Numbers: 2026P000457; 5P30AG064199-07 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No