Registry-Based Pragmatic Trials in Heart Failure: Current Experience and Future Directions

Abstract

Purpose of review: Randomized controlled trials (RCTs) in heart failure (HF) are becoming increasingly complex and expensive to conduct and if positive deliver expensive therapy tested only in selected populations.

Recent findings: Electronic health records and clinical cardiovascular quality registries are providing opportunities for pragmatic and registry-based prospective randomized clinical trials (RRCTs). Simplified regulatory, ethics, and consent procedures; recruitment integrated into real-world care; and simplified or automated baseline and outcome collection allow assessment of study power and feasibility, fast and efficient recruitment, delivery of generalizable findings at low cost, and potentially evidence-based and novel use of generic drugs with low costs to society. There have been no RRCTs in HF to date. Major challenges include generating funding, international collaboration, and the monitoring of safety and adherence for chronic HF treatments. Here, we use the Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure with Preserved Ejection Fraction (SPIRRIT-HFpEF), to be conducted in the Swedish Heart Failure Registry, to exemplify the advantages and challenges of HF RRCTs.

Keywords: Cost; Heart failure; Pragmatic clinical trial; Prospective randomized clinical trial; Registry; Registry-based pragmatic trial; Registry-based prospective randomized clinical trial.

Fig. 1

Characteristics or RCTs and registries, and advantages of RRCTs. Each item is discussed in text. RCT prospective randomized controlled trial, RRCT registry-based prospective randomized controlled trial, CRO contract research organization, HF heart failure, M million, ARO academic research organization

Fig. 2

The integrated platform for RRCTs in the Swedish Heart Failure Registry. New patients are entered into the registry, and the platform screens and determines eligibility for both [1] previously entered and living patients, and [•] online as new patients are entered. Eligibility is fed back to the investigator in the registry, in the form of [1] lists of existing eligible patients and [•] online as entered patients are determined to be eligible. The investigator collects informed consent, the platform randomizes online and the investigator implements the randomized assignment and follows the patient in routine clinical care (with or without extra trial-specific follow-up). The baseline data entered into the registry as part of routine care together with randomized assignment are fed into a separate electronic data capture (EDC) system in the RRCT platform. The unique personal ID number is fed to the independent registries in the Swedish Board of Health and Welfare, which feeds back outcomes (deaths and causes, hospitalization and causes, new diagnoses, and medication use and randomized medication assignment adherence) to the EDC in the platform. Baseline and outcome data are then analyzed, provided to an independent data monitoring committee (DMC), and published. SwedeHF The Swedish Heart Failure Registry, RRCT registry-based randomized controlled trial