Comparison of Gadoterate Meglumine and Gadobutrol in the MRI Diagnosis of Primary Brain Tumors: A Double-Blind Randomized Controlled Intraindividual Crossover Study (the REMIND Study)

Abstract

Background and purpose: Effective management of patients with brain tumors depends on accurate detection and characterization of lesions. This study aimed to demonstrate the noninferiority of gadoterate meglumine versus gadobutrol for overall visualization and characterization of primary brain tumors.

Materials and methods: This multicenter, double-blind, randomized, controlled intraindividual, crossover, noninferiority study included 279 patients. Both contrast agents (dose = 0.1 mmol/kg of body weight) were assessed with 2 identical MRIs at a time interval of 2-14 days. The primary end point was overall lesion visualization and characterization, scored independently by 3 off-site readers on a 4-point scale, ranging from "poor" to "excellent." Secondary end points were qualitative assessments (lesion border delineation, internal morphology, degree of contrast enhancement, diagnostic confidence), quantitative measurements (signal intensity), and safety (adverse events). All qualitative assessments were also performed on-site.

Results: For all 3 readers, images of most patients (>90%) were scored good or excellent for overall lesion visualization and characterization with either contrast agent; and the noninferiority of gadoterate meglumine versus gadobutrol was statistically demonstrated. No significant differences were observed between the 2 contrast agents regarding qualitative end points despite quantitative mean lesion percentage enhancement being higher with gadobutrol (P < .001). Diagnostic confidence was high/excellent for all readers in >81% of the patients with both contrast agents. Similar percentages of patients with adverse events related to the contrast agents were observed with gadoterate meglumine (7.8%) and gadobutrol (7.3%), mainly injection site pain.

Conclusions: The noninferiority of gadoterate meglumine versus gadobutrol for overall visualization and characterization of primary brain tumors was demonstrated.

Fig 1.

Patient disposition with numbers of patients enrolled (n = 279) and randomized (n = 274) to undergo 2 identical MR imaging examinations with gadoterate meglumine followed by gadobutrol (arm 1) or with gadobutrol followed by gadoterate meglumine (arm 2). A total of 268 patients received the first contrast agent injection, and 249 patients completed the study with the 2 examinations performed.

Fig 2.

Rate of patients with overall lesion visualization and characterization scored good/excellent or poor/fair. The bar graph shows the rate of patients with overall lesion visualization and characterization scored good/excellent or poor/fair according to each contrast agent and each off-site reader (n = 234 patients for all readers).

Fig 3.

A 46-year-old woman with glioblastoma. T1 spin-echo images (1.5T) after administration of 0.1 mmol/kg of gadoterate meglumine (A) and gadobutrol (B) show an approximate 65-mm lesion. The time between the 2 MR imaging examinations was 7 days. Lesion visualization and characterization were scored as excellent by all 3 blinded readers. The enhancing rim of the lesion is clearly seen on both examinations.

Fig 4.

A 74-year-old man with a high-grade glioma. T1 spin-echo images (1.5T) after administration of 0.1 mmol/kg of gadoterate meglumine (A) and gadobutrol (B) show an approximate 30-mm mass. The time between the 2 MR imaging examinations was 8 days. Lesion visualization and characterization were scored as excellent by all 3 blinded readers. The mass is clearly seen on both examinations and shows no difference in contrast enhancement.

Fig 5.

Classification in preference subgroups for lesion border delineation (A), lesion internal morphology (B), and degree of contrast enhancement (C). The bar graphs show the rate of patients classified in preference subgroups for lesion border delineation (A), lesion internal morphology (B), and degree of contrast enhancement (C), according to each off-site reader (n = 234 patients for all readers; n = 231 patients for reader 1; n = 233 patients for reader 2; n = 232 patients for reader 3), with P > .1 for the 3 end points for all readers (Wilcoxon signed rank test).