Comparison of 1.0 M gadobutrol and 0.5 M gadopentetate dimeglumine-enhanced magnetic resonance imaging in five hundred seventy-two patients with known or suspected liver lesions: results of a multicenter, double-blind, interindividual, randomized clinical phase-III trial.
OBJECTIVE
To evaluate the diagnostic efficacy (accuracy, sensitivity, specificity) of 1.0 M gadobutrol versus 0.5 M gadopentetate for the classification of lesions as either benign or malignant in patients with known or suspected liver lesions.


METHODS
A multicenter, phase-III, randomized, interindividually controlled comparison study with blinded reader evaluation was performed to investigate the diagnostic efficacy of a bolus injection of 1.0 M gadobutrol compared with 0.5 M gadopentetate at a dose of 0.1 mmol Gd/kg BW. The imaging protocol included a dynamic 3D-evaluation, static conventional, and fat saturated T1-weighted sequences. MR datasets were evaluated by 3 independent radiologists. The standard of reference was defined by an independent truth panel (radiologist or hepatologist). The safety evaluation included adverse events, vital signs, and physical examination.


RESULTS
A total of 497 of 572 patients were eligible for the final efficacy analysis. Noninferiority of gadobutrol-enhanced magnetic resonance imaging (MRI) for the classification of liver lesions was demonstrated on the basis of diagnostic accuracy determined by the on-site investigators (-0.098, 0.021) as well as for the average reader of the blinded evaluation (-0.096, 0.014) (95% confidence interval), compared with the predefined standard of reference. Very similar increases in sensitivity (ranging from approximately 10% to approximately 55%) and specificity (ranging from approximately 1% to approximately 18%) compared with precontrast MRI were also observed for the 2 contrast agent groups, with maximum differences of 4%.Very similar, low rates of adverse events were recorded for each of the 2 groups. No clinically relevant changes in vital signs or the results of the physical examination were observed in any patient.


CONCLUSIONS
This study documents evidence for the noninferiority of a single i.v. bolus injection of 1.0 M gadobutrol (0.1 mmol/kg body weight) to 0.5 M gadopentetate (0.1 mmol/kg body weight) in the diagnostic assessment of liver lesions with contrast-enhanced MRI. The known excellent safety profile of gadobutrol was confirmed in this clinical trial and is similar to that of gadopentetate.
Hammerstingl
Renate
R
Department of Diagnostic and Interventional Radiology, Johann Wolfgang Goethe University Hospital, Frankfurt am Main, Germany. Hammerstingl@em.uni-frankfurt.de
Adam
Gerhard
G
Ayuso
Juan-Ramon
JR
Van Beers
Bernard
B
Belfiore
Giuseppe
G
Bellin
Marie-France
MF
Bongartz
Georg
G
Ernst
Olivier
O
Frericks
Bernd
B
Giuseppetti
Gianmarco
G
Heinz-Peer
Gertrud
G
Laghi
Andrea
A
Martin
Julio
J
Pering
Christiane
C
Reimer
Peter
P
Richter
Götz-Martin
GM
Roemer
Frank W
FW
Schäfer
Fritz K W
FK
Vilgrain
Valérie
V
Vogl
Thomas J
TJ
Weishaupt
Dominik
D
Wall
Alexander
A
Zech
Christoph J
CJ
Tombach
Bernd
B
D003287:Contrast Media; D004311:Double-Blind Method; D005060:Europe / Q000453:epidemiology; D005260:Female; D019786:Gadolinium DTPA / Q000008:administration & dosage; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data*; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000008:administration & dosage; D015995:Prevalence; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D003287:Contrast Media; D009942:Organometallic Compounds; C090600:gadobutrol; D019786:Gadolinium DTPA