Subanalysis of Cardiac MRI of a phase 3 trial investigating safety and efficacy of gadoquatrane for low-dose contrast-enhanced MRI of the body

Background: To investigate the safety and efficacy of gadoquatrane, a new low-dose macrocyclic gadolinium-based contrast agent (mGBCA) at a dose of 0.04 mmol gadolinium (Gd)/kg body weight (bw) compared to 0.1 mmol Gd/kg bw of approved mGBCAs (gadobutrol, gadoterate, gadoteridol) for contrast-enhanced MRI (CE-MRI) in adults, including cardiac lesions.

Methods: This phase 3 study was a multicenter, randomized, prospective double-blind, cross-over study. Adult patients with a known or suspected pathology of any body region (except CNS) underwent two contrast-enhanced-MRIs (CE-MRI), one with gadoquatrane and the other with a comparator mGBCA in random order with a washout period of 3 to 14 days. Mandatory study images for each MRI were unenhanced T1w-sequence (pre-contrast) and enhanced T1w-sequence. Other image series according to site’s standard of care could be acquired as well. Image assessments of the cardiac subpopulation were performed by three blinded central readers who were experts in cardiovascular MRI. For all study cases combined (including pre- and post-contrast images) and pre-contrast MR image sets were assessed using the same three qualitative visualization parameters as primary endpoints: contrast enhancement, delineation and morphology. Late gadolinium enhancement (LGE) lesions were scored on a 4- (contrast enhancement, delineation) or 3-point scale (morphology). Analyses (including linear mixed effects model to analyze the differences in mean scores and their corresponding 95% CIs) were conducted for all lesions as well as for matching lesions between pre-contrast and combined gadoquatrane as well as combined gadoquatrane and comparator image sets. Safety parameters such as adverse events and laboratory parameters were recorded.

Results: Of 410 randomized study patients, 36 underwent cardiac MRI and were evaluable for efficacy analysis; mean age was 54.0 years, 36.1% were female. Referral diagnoses included hypertrophic or dilatative cardiomyopathies, myocarditis, ischemia and others. The comparison of gadoquatrane vs. comparator resulted in similar mean scores for the visualization parameters with a difference close to 0 for all 3 readers, indicating comparable efficacy. For the comparison of gadoquatrane vs. pre-contrast, the mean scores showed a clear improvement for all visualization parameters with differences in mean scores between gadoquatrane and pre-contrast MR image sets being close to or greater than 1 for all readers, indicating improved visualization of lesions with gadoquatrane MRI. The safety profile was similar for gadoquatrane and comparators and consistent with the known safety profile of mGBCAs.

Conclusion: Gadoquatrane at a dose of 0.04 mmol Gd/kg bw, offering a 60% reduction in Gd dose compared to comparator mGBCAs, exhibits similar efficacy and safety profile to that of comparator mGBCAs for CE-MRI lesions of the heart using LGE.

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