Evaluating dyNamic myocardial blood flow qUantitation as a Cost-effective care modeL for diabEtic patients with coronary artery diSease (NUCLEuS): A randomized controlled trial - Rationale and Design

Background: Recent advancements in quantifying myocardial blood flow (MBF) and coronary flow reserve using dynamic SPECT MPI have demonstrated comparable hemodynamic correlations with invasive angiography and PET. Implementation into routine practice, however, imposes attendant demands on resources. Diabetes mellitus is a rising pandemic associated with accelerated atherosclerosis, yet there is potential for under-detection of significant ischemia. Objectives: We postulate that quantifying myocardial blood flow (MBF) by dynamic SPECT reduces post-test resource utilization and improve economic efficiency over conventional SPECT. Methods: NUCLEuS is an ongoing prospective open-label randomized clinical trial that will enroll 300 diabetic patients without known coronary artery disease (CAD) referred clinically for SPECT MPI from March 2022 to March 2025. The aim is to determine the incremental prognostic value and post-test resource utilization of dynamic MBF over conventional SPECT in diabetic patients with suspected CAD. The primary endpoint is diagnostic failure, defined as unnecessary coronary angiography (absence of >= 50% stenosis in >= 1 coronary artery) or additional anatomical testing (e.g., coronary computed tomography angiography) within 90 days. Secondary endpoints are referrals for angiography or revascularization, escalation of anti-anginal medications, and quality-of-life scores at 12 months. Long-term endpoints are major adverse cardiovascular events (cardiac mortality, myocardial infarction, unstable angina, revascularization) within 36 months. The incremental costeffectiveness ratio will be estimated based on cost and clinical effectiveness. Conclusions: NUCLEuS will be an imaging-directed clinical trial that will compare differences in outcomes and resource utilization of dynamic MBF over conventional SPECT MPI in the routine clinical management of CAD in diabetes mellitus.