MR angiography with gadofosveset trisodium for peripheral vascular disease: phase II trial.
OBJECTIVE
To evaluate the dose response and safety of gadofosveset trisodium-enhanced magnetic resonance (MR) angiography compared with nonenhanced two-dimensional time-of-flight MR angiography and with x-ray angiography as the standard.


METHODS
In this randomized, 20-center, double-blind study, 238 men and women who had peripheral vascular disease or were suspected of having it received intravenous injection of placebo or gadofosveset (0.005, 0.01, 0.03, 0.05, or 0.07 mmol per kilogram of body weight). MR angiographic images were evaluated by three blinded readers, and x-ray angiographic images were evaluated by two readers. Hypothesis testing for the presence of a dose response was based on a linear test for trend for increase in area under the receiver operating characteristic curve as a function of dose for each reader of MR angiographic images independently.


RESULTS
Gadofosveset administration resulted in a dose-dependent increase in diagnostic accuracy for detection of aortoiliac occlusive disease as reflected in the area under the receiver operating characteristic curve for each reader (P <.001). The plateau in effectiveness improvement began at the 0.03 mmol/kg dose. At doses of 0.03 mmol/kg and higher, gadofosveset-enhanced MR angiography provided an approximate 20% increase in accuracy over nonenhanced MR angiography for diagnosis of clinically significant aortoiliac occlusive disease. Gadofosveset exhibited a good safety profile in all dose groups. Three serious adverse events were possibly or probably related to gadofosveset administration. There were no dose-related trends in severe or serious adverse events in patients receiving gadofosveset.


CONCLUSIONS
A dose of 0.03 mmol/kg of gadofosveset was safe and effective for evaluation of aortoiliac occlusive disease with MR angiography.
Department of Radiology, CHUM-Hospital St Luc, Montreal, Quebec, Canada.
Pierre
P
Perreault
Mark A
MA
Edelman
Richard A
RA
Baum
E Kent
EK
Yucel
Robert M
RM
Weisskoff
Kohkan
K
Shamsi
Emile R
ER
Mohler
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000792:Angiography; D003287:Contrast Media; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005682:Gadolinium; D006801:Humans; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000009:adverse effects; D016491:Peripheral Vascular Diseases / Q000175:diagnosis* / Q000000981:diagnostic imaging; D012372:ROC Curve; D012449:Safety
D003287:Contrast Media; D009942:Organometallic Compounds; D005682:Gadolinium; C109932:gadofosveset trisodium