Abstract
BACKGROUND. Gadobutrol and gadoterate are widely used macrocyclic gadolinium-based contrast agents. Given gadobutrol’s higher T1 relaxivity, a reduced gadobutrol dose should achieve essentially equivalent diagnostic efficacy as a standard dose of gadoterate. OBJECTIVE. The purpose of our study was to show efficacy of a 25% reduced dose of gadobutrol is noninferior to 100% standard dose of gadoterate for contrast-enhanced MRI of the CNS. METHODS. In this international prospective multicenter open-label crossover trial (LEADER-75 [Lower Administered Dose With Higher Relaxivity: Gadovist vs Dotarem]), adult patients with known or suspected CNS pathology underwent contrast-enhanced brain MRI with standard-dose gadoterate (0.1 mmol/kg); if an enhancing lesion was identified, a second MRI with reduced-dose gadobutrol (0.075 mmol/kg) was performed within 15 days of the first MRI. Three radiologists independently reviewed images to score three primary efficacy measures: subjective lesion enhancement, lesion border delineation, lesion internal morphology. A noninferiority analysis used readers’ mean scores of the primary efficacy measures. Noninferiority of reduced-dose gadobutrol to standard-dose gadoterate for primary efficacy measures was defined as the difference in score between reduced-dose gadobutrol images and unenhanced images achieving at least 80% of the difference in score between standard-dose gadoterate images and unenhanced images. A post hoc analysis was performed to directly compare contrast-enhanced images for equivalence. Secondary efficacy variables included the number of lesions detected, reader confidence, diagnostic performance for malignancy, and reader preference in side-by-side comparison. RESULTS. The efficacy analysis included 141 patients (78 men, 63 women; mean age, 58.5 ± 13.5 [SD] years). Improvement of reduced-dose gadobutrol over unenhanced images was noninferior to improvement of standard-dose gadoterate over unenhanced images using a 20% noninferiority margin for all three primary efficacy measures using mean readings (p ≤ .025). In the post hoc analysis, the mean reading for the three primary efficacy measures differed by less than 1% between reduced-dose gadobutrol and standard-dose gadoterate, supporting equivalence of all measures using a narrow ± 5% margin (p ≤ .025). The total number of lesions detected by mean reading was 301 for reduced-dose gadobutrol versus 291 for standard-dose gadoterate. Mean reader confidence was 3.3 ± 0.6 for reduced-dose gadobutrol versus 3.3 ± 0.6 for standard-dose gadoterate. Sensitivity (58.7%), specificity (91.8%), and accuracy (70.2%) for malignancy from majority reading were identical for reduced-dose gadobutrol and standard-dose gadoterate. Reader preference was not different (95% CI, –0.10 to 0.11). CONCLUSION. A 25% reduced dose of gadobutrol is noninferior to standard-dose gadoterate for contrast-enhanced brain MRI.
Original language | English (US) |
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Pages (from-to) | 1195-1205 |
Number of pages | 11 |
Journal | American Journal of Roentgenology |
Volume | 217 |
Issue number | 5 |
DOIs | |
State | Published - Nov 2021 |
Funding
Submitted: Mar 24, 2021 Revision requested: Apr 3, 2021 Revision received: Apr 30, 2021 Accepted: May 28, 2021 First published online: Jun 16, 2021 B. P. Liu, P. Saverio, Y. C. Weon, S. Peters, and F. D. Ardellier are investigators of the LEADER-75 trial. B. P. Liu received research grants from Guerbet and Bayer AG. M. Rosenberg, A. Boeckenhoff, and J. Endrikat are employees of Bayer AG. F. D. Ardellier received support from Guerbet and Bayer AG for scientific advice. The remaining author declares that there are no disclosures relevant to the subject matter of this article. We thank all patients who participated in the LEADER-75 trial and all active principal investigators (Amit Agarwal, Mirco Cosottini, Fran?ois Cotton, Francesco Di Paola, Arnd Doerfler, Karl-Titus Hoffmann, Olav Jansen, Sangam Kanekar, Klaus Kirchhof, St?phane Kremer, Soenke Langner, Sachin Mathur, Kambiz Nael, Luca Remonda, Tommaso Scarabino, Peter Schramm, Roland Wiest, Seung Hong Choi). We also thank Alice Isejima (study manager), Daniel Haverstock (statistics), Michael Kunz (statistics), and Jan Mallow (imaging operations and support).
Keywords
- CNS
- Dose
- Gadobutrol
- Gadoterate
- MRI
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging