International Phase II Cardiac Safety Trial With Cardiac MRI

Challenge

An international Phase II trial required cardiac MRI to assess the cardiac safety and tolerability of a novel drug. The endpoint depended on detecting small changes in left ventricular ejection fraction, volumes and mass over the treatment period, measurements that vary with scanner vendor, sequence parameters, slice planning and contouring convention.

Across 30 sites with differing cardiac MRI experience, the sponsor needed acquisition standardized enough to make serial measurements comparable, contouring consistent enough that a change of a few percentage points in ejection fraction would be meaningful, and reporting fast enough to feed the trial's safety monitoring.

Intrinsic Imaging’s Solution

Intrinsic Imaging's cardiovascular team designed the imaging charter around a standardized cine cardiac MRI protocol with defined short-axis coverage, slice thickness, temporal resolution and breath-hold technique, and provided site-specific guidance for each vendor platform. Sites were qualified on test acquisitions reviewed for slice planning and image quality.

Cardiologists and radiologists with cardiac MRI expertise performed quantitative analysis under a reading charter that fixed contouring conventions for endocardial and epicardial borders, papillary muscle handling and phase selection. Each patient was followed by the same primary analyst, with a second analyst on a prespecified sample to document reproducibility, and qualitative review captured pericardial, valvular and myocardial findings.

Image transfer and quality control were centralized with acquisition feedback to sites, and safety-relevant changes in ventricular function were reported to the sponsor on a defined schedule.

Intrinsic Imaging’s Results

• Cardiac MRI standardized across 30 sites in 7 countries with vendor-specific acquisition guidance
• Approximately 620 examinations quantified for LVEF, volumes and mass under fixed contouring conventions
• Inter-analyst reproducibility of LVEF within 3 percentage points documented on a 15% double-analysis sample
• Unevaluable examinations held under 4% through site qualification and rapid acquisition feedback