title: Phase 3 efficacy and safety trial of gadobutrol, a 1.0 molar macrocyclic MR imaging contrast agent, in patients referred for contrast-enhanced MR imaging of the central nervous system.
abstract: OBJECTIVE
  Gadobutrol is a 1.0 M macrocyclic magnetic resonance imaging (MRI) contrast agent. A study was performed to evaluate the efficacy and safety of gadobutrol-enhanced versus unenhanced imaging for central nervous system (CNS) lesion visualization and detection.
  
  
  METHODS
  An international, multicenter, open-label, Phase III clinical trial. Patients underwent unenhanced and gadobutrol 1.0 M-enhanced (0.1 mmol/kg BW) MR imaging using a standardized protocol. Unenhanced and combined unenhanced/gadobutrol-enhanced images were scored by three independent, blinded readers for degree of lesion enhancement, border delineation, internal morphology, and total number of lesions detected (primary efficacy variables). Exact match of the MR diagnoses with the final clinical diagnosis, detection of malignant CNS lesions, and confidence in diagnosis were secondary efficacy variables.
  
  
  RESULTS
  Of 343 enrolled patients, 321 were evaluated for efficacy. All primary efficacy endpoints were met: superiority was demonstrated for gadobutrol-enhanced versus unenhanced MR images (P < 0.0001 in all cases) for lesion enhancement, border delineation, and internal morphology. Noninferiority was met for mean number of lesions detected. There were improvements in the sensitivity of malignant lesion detection, without a loss in specificity, exact-match diagnostic accuracy, and reader confidence. Treatment-related adverse events were reported in 4.1% (n = 14); all were nonserious.
  
  
  CONCLUSIONS
  Gadobutrol 1.0M is an effective and well-tolerated contrast agent for CNS MRI.
authors.affiliation: Neuroradiology Section, The University of Texas Health Science Center at San Antonio, Texas, USA.
authors.forename: Juan E
authors.initials: JE
authors.lastname: Gutierrez
authors.forename: Martin
authors.initials: M
authors.lastname: Rosenberg
authors.forename: Michael
authors.initials: M
authors.lastname: Duhaney
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Simon
authors.forename: Guenther
authors.initials: G
authors.lastname: Brueggenwerth
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Agris
authors.forename: Edmond A
authors.initials: EA
authors.lastname: Knopp
mesh_terms: D001118:Argentina; D016543:Central Nervous System Neoplasms / Q000175:diagnosis*; D002681:China; D003105:Colombia; D003287:Contrast Media; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D009942:Organometallic Compounds; D015203:Reproducibility of Results; D056910:Republic of Korea; D012680:Sensitivity and Specificity; D014481:United States
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; C090600:gadobutrol
keywords: MRI; contrast-enhanced; gadobutrol; unenhanced imaging