Invasive or Non-Invasive Coronary Angiography in Stable Patients with High Clinical Likelihood of Coronary Artery Disease According to European Guidelines (INCHARGE): Randomised Controlled Assessor-Blinded Multicentre Trial

• Applicant: Professor Dr. Marc Dewey
• Subject Area: Radiology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 567888473

Background and Objectives: Based on the randomised controlled DISCHARGE and SCOT-HEART trials, computed tomography angiography (CTA) is now recommended for routine practice in Germany in patients with intermediate likelihood of obstructive coronary artery disease (CAD). In patients with high clinical likelihood of CAD, there is equipoise for CTA or ICA according to an international Delphi-based clinical consensus statement. No randomized controlled trials have been done in this population. Thus, the objective of INCHARGE is to investigate the effectiveness of CTA in patients with high likelihood of CAD referred for ICA. Methods and Work Program: We propose an international 16-centre randomized trial comparing CTA and ICA for guiding treatment in 3376 patients at least 30 years of age referred for ICA with stable chest pain and a high clinical likelihood of obstructive CAD. Meeting at least one of the guideline criteria of high clinical likelihood will be the basis for inclusion: (i) angina refractory to medical therapy, (ii) typical angina at low level of exercise, (iii) positive functional testing indicating high risk, or (iv) left ventricular dysfunction suggestive of CAD. Exclusion criteria will be known obstructive or treated CAD, previous normal ICA or CT within the last 5 years, inability to undergo CT or ICA, and pregnancy. The primary hypothesis is that CTA will be non-inferior to ICA, with hierarchical testing for superiority, for major adverse cardiovascular events (MACE) defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, based on MACE incidences and a sub-distribution hazard ratio of 0.7 observed in DISCHARGE. Following the recommendation of the statistical reviewer, we recalculated the sample size using the Weibull distribution for non-inferiority trials. Furthermore, the Aalen-Johansen estimator will be used to calculate the cumulative incidence of MACE. As a sensitivity analysis we will follow the advice in Tröndle et al. and fit a Cox model for MACE which treats competing events as independent censoring. Several mechanisms seen in previous trials could lead to the proposed non-inferiority of CTA: greater use of preventative therapy, increased use of functional testing, and more targeted revascularization. Moreover, CTA may also facilitate planning of revascularisation. Death from CAD or nonfatal spontaneous myocardial infarction will be the efficacy outcome measure. The safety outcome measure will be major procedure-related complications including those related to downstream testing or revascularization procedures including procedural myocardial infarction or stroke. Secondary outcomes also include quality of life (EQ-5D) and angina (SAQ-7). Anticipated Gain of Knowledge: If the proposed study shows that if compared to ICA, CTA is non-inferior for MACE with fewer complications, or is indeed superior for MACE, this will fundamentally alter the diagnostic strategy in patients with suspected CAD.

• DFG Programme: Clinical Trials