A multi-center, comparative, phase 3 study to determine the efficacy of gadofosveset-enhanced magnetic resonance angiography for evaluation of renal artery disease

Abstract

PurposeTo determine prospectively the safety and efficacy of the blood-pool contrast agent gadofosveset trisodium in renal artery magnetic resonance angiography (MRA). Materials and methodsGadofosveset (0.03mmol/kg) was administered to adult patients with known or suspected renal arterial disease in a multi-center phase 3 single dose study. The drug binds reversibly to albumin, prolonging the blood residence time, and allowing collection of images in the first-pass and steady-state phases. The combination of these images was compared to non-contrast MRA, using catheter X-ray angiography (XRA) as the standard of reference (SOR). All MRA images were collected at 1.5T in one imaging session for direct comparison, and XRA within 30 days. Sensitivity, specificity, and accuracy for diagnosing significant disease (stenosis ≥50%) were calculated for MRA using three independent blinded readers. Patient safety was monitored for 72–96h. ResultsA total of 145 patients at 18 centers were enrolled and received gadofosveset; the 127 with complete efficacy data entered the primary efficacy analysis. Gadofosveset-enhanced MRA led to significant improvement (p<0.01) in sensitivity (+25%, +26%, +42%), specificity (+23%, +25%, +29%), and accuracy (+23%, +28%, +29%) over non-enhanced MRA for the three readers. The rate of uninterpretable examinations decreased from 30% to less than 2%. There were no serious adverse events, and the most common adverse events were nausea, pruritis, and headache (8% each). No significant trends in clinical chemistry parameters, nor significant changes in serum creatinine, were found following administration of gadofosveset. ConclusionIn patients with known or suspected renal arterial disease, multi-phase gadofosveset-enhanced MRA significantly improves sensitivity, specificity, and accuracy versus non-enhanced MRA. Gadofosveset was safe and well tolerated in this patient population.