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

Purpose: To determine prospectively the safety and efficacy of the blood-pool contrast agent gadofosveset trisodium in renal artery magnetic resonance angiography (MRA).

Materials And Methods: Gadofosveset (0.03 mmol/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 1.5 T in one imaging session for direct comparison, and XRA within 30 days. Sensitivity, specificity, and accuracy for diagnosing significant disease (stenosis > or =50%) were calculated for MRA using three independent blinded readers. Patient safety was monitored for 72-96 h.

Results: A 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, pruritus, and headache (8% each). No significant trends in clinical chemistry parameters, nor significant changes in serum creatinine, were found following administration of gadofosveset.

Conclusion: In 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.