Comparison of 1.0 M Gadobutrol and 0.5 M Gatopentetate Dimeglumine – enhanced magnetic resonance imaging in five hundred seventy-two patients with known of suspected liver lesions: results of a multicenter, duble-blind, interindividual, randomized clinical phase III trial

Investigative Radiology: March 2009 - Volume 44 - Issue 3 - pp 168-176 doi: 10.1097/RLI.0b013e318198a0ae Original Article 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 Hammerstingl, Renate MD*; Adam, Gerhard MD†; Ayuso, Juan-Ramon MD‡; Van Beers, Bernard MD§; Belfiore, Giuseppe MD¶; Bellin, Marie-France MD∥; Bongartz, Georg MD**; Ernst, Olivier MD‡‡; Frericks, Bernd MD¶¶¶¶; Giuseppetti, Gianmarco MD§§; Heinz-Peer, Gertrud MD∥∥; Laghi, Andrea MD†††; Martin, Julio MD***; Pering, Christiane MD‡‡‡; Reimer, Peter MD§§§; Richter, Götz-Martin MD∥∥∥; Roemer, Frank W. MD****; Schäfer, Fritz K. W. MD¶¶; Vilgrain, Valérie MD††††; Vogl, Thomas J. MD*; Weishaupt, Dominik MD‡‡‡‡; Wall, Alexander MD§§§§; Zech, Christoph J. MD¶¶¶; Tombach, Bernd MD§§§§∥∥∥∥ Abstract 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 and Materials: 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 ∼10% to ∼55%) and specificity (ranging from ∼1%-∼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. Conclusion: 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.