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

Official title

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

Overview

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.

Interventions

• 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
• 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.

Primary outcome measures

• Maximum beta-blocker dose achieved [Time frame: 120 days]

Secondary outcome measures (1)

• Proportion of participants taking >50% of target dose [Time frame: 120 days]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Health services research

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07489352 · 2026P000457 · 5P30AG064199-07

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗