Aortoiliac occlusive disease in patients with known or suspected peripheral vascular disease: safety and efficacy of gadofosveset-enhanced MR angiography--multicenter comparative phase III study.
OBJECTIVE
To prospectively determine the safety and efficacy of the gadolinium-based blood pool magnetic resonance (MR) imaging contrast agent gadofosveset in patients known to have or suspected of having peripheral vascular disease.


METHODS
Ethical committee approval and patient written informed consent were obtained. This study was compliant with the Health Insurance Portability and Accountability Act. Adults known or suspected to have peripheral vascular disease received gadofosveset (0.03 mmol per kilogram of body weight) for MR angiography of the aortoiliac region. Gadofosveset-enhanced MR angiography and unenhanced two-dimensional time-of-flight MR angiography were compared with the reference standard, conventional angiography, for the presence of vascular stenosis. All patients were monitored for adverse events with hematologic analysis, analysis of blood chemistry, urinalysis, and electrocardiographic parameters; these methods were analyzed to determine safety.


RESULTS
A total of 274 patients were enrolled at 37 centers. Gadofosveset-enhanced MR angiography showed significant improvement (P < .001) compared with unenhanced MR angiography for each of the readers for diagnosis of clinically significant (> or = 50%) stenosis. Specificity and accuracy were significantly greater for three readers, and sensitivity increased significantly for two readers. For all readers, the area under the receiver operator characteristic curve for both quantitative and qualitative measures of significant disease increased (P < .001) for gadofosveset-enhanced MR angiography versus two-dimensional time-of-flight MR angiography. All readers also expressed more confidence in diagnosis (P < .001) and found fewer images to be uninterpretable (0.5% vs 11.0%). The most common adverse events were as follows: feeling hot, 12 (4.4%) patients; nausea, 10 (3.6%) patients; headache, nine (3.3%) patients; and burning sensation, eight (2.9%) patients. Only four serious adverse events were reported, in three patients, and all events were rated as unlikely related to the drug. No patients were excluded because of adverse events or laboratory abnormalities. There were no clinically important trends in the findings of hematologic analysis, blood chemistry, urinalysis, electrocardiography, or physical examination.


CONCLUSIONS
On the basis of substantial improvements over non-contrast MR angiography in efficacy and a minimal and transient side-effect profile, gadofosveset was found to be safe and effective for MR angiography in patients known or suspected to have peripheral vascular disease.
Rapp
Joseph H
JH
Surgical Service (112G San Francisco DVA Medical Center, 4150 Clement St, San Francisco, CA 94121, USA. rappj@surgery.ucsf.edu
Wolff
Steven D
SD
Quinn
Stephen F
SF
Soto
Jorge A
JA
Meranze
Steven G
SG
Muluk
Satish
S
Blebea
John
J
Johnson
Stephen P
SP
Rofsky
Neil M
NM
Duerinckx
Andre
A
Foster
Gregory S
GS
Kent
K Craig
KC
Moneta
Gregory
G
Middlebrook
Michael R
MR
Narra
Vamsidhar R
VR
Toombs
Barry D
BD
Pollak
Jeffrey
J
Yucel
E Kent
EK
Shamsi
Kohkan
K
Weisskoff
Robert M
RM
D000368:Aged; D015901:Angiography, Digital Subtraction; D001018:Aortic Diseases / Q000175:diagnosis* / Q000209:etiology; D001157:Arterial Occlusive Diseases / Q000175:diagnosis* / Q000209:etiology; D003287:Contrast Media; D005260:Female; D005682:Gadolinium; D006801:Humans; D007083:Iliac Artery; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds; D016491:Peripheral Vascular Diseases / Q000150:complications*; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity
D003287:Contrast Media; D009942:Organometallic Compounds; D005682:Gadolinium; C109932:gadofosveset trisodium