A registry-based randomized clinical trial for heart failure treatment using the Swedish Heart Failure Registry
31 Mar 2017

Electronic health records and clinical cardiovascular quality registries provide opportunities for pragmatic clinical trial (PCT) and registry-based prospective randomized clinical trials (RRCTs). Simplified regulatory, ethics, and consent procedures as well as 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 few RRCTs in heart failure (HF) to date. Major challenges include generating funding, international collaboration, and the monitoring of safety and adherence for chronic HF treatments.

The Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure with Preserved Ejection Fraction (SPIRRIT-HFpEF) is an RRCT under development in the Swedish Heart Failure Registry. It is a phase 4 randomized multicentre trial which will assess safety and efficacy. The trial design is interventional with parallel assignment, an intention-to-treat group, open-label treatment, and event-driven analysis, in HFpEF. The primary objective is to test spironolactone with standard care vs. standard care alone in patients with HF and EF ≥40%. To our knowledge, this is the first registry-based trial in HF.

The integrated platform for RRCTs in the Swedish Heart Failure Registry:

•             New patients are entered the registry, and the platform screens and determines eligibility for both 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 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 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.


Source: Lund LH, Oldgren J, James S. Registry-Based Pragmatic Trials in Heart Failure: Current Experience and Future Directions. Curr Heart Fail Rep. 2017 Feb 28;1–12.