Non-participation in a Heart Failure Clinical Trial: Perspectives and Opportunities from the VICTORIA Trial and Simultaneous Registry

Background Randomized controlled trials (RCT) often enroll patients with different demographics and outcomes than a broader non-RCT population. To provide context for the VICTORIA RCT, we designed a registry of patients with worsening heart failure (WHF) to characterize baseline characteristics, outcomes, and potential reasons for non-participation in a RCT. Methods 51 VICTORIA RCT sites were selected from Canada and the US. Eligible patients for the registry included those with chronic HF, currently or recently hospitalized for HF, and EF Results 2056 patients were enrolled in the registry, of whom 61% (n = 1256) were not eligible for the RCT, 37% (n = 766) were eligible but not enrolled, and 2% (n = 34) were enrolled in the RCT. Registry patients had a median age of 70, 33% were women, 63% were white, 48% had atrial fibrillation on ECG, and 59% had CAD. Median EF was 25%, median eGFR was 50 ml/min/1.73m2 and median NT-proBNP at discharge was 4376 pg/ml. The median MAGGIC risk score was 28 (23-32) indicating a 20.9% (13.4-29.2%) predicted 1-year mortality, similar to the all-cause mortality seen in the VICTORIA RCT (21.2%). Reasons for ineligibility in the RCT included long-acting nitrate use (23%), SBP Fig ). For eligible patients, reasons for non-participation in the RCT included lack of interest (28%), poor compliance (25%), inability to complete follow-up (23%), too sick (19%), unable to provide consent (17%), and distance from site (15%). Conclusions Patients with WHF in a contemporaneous registry exhibit high-risk features with many having modifiable reasons for exclusion from an RCT. Several reasons for non-participation in an RCT indicate opportunities for improving enrollment to ensure generalizability.