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Phase 3 N=402 Randomized Quadruple-blind Diagnostic

Safety and Efficacy of Gadobutrol 1.0 Molar (Gadavist) in Patients for Central Nervous System (CNS) Imaging

Diagnostic Imaging · Central Nervous System Diseases

Enrolled (actual)
402
Serious AEs
0.4%
Results posted
Mar 2012
Primary outcome: Primary: Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced Magnetic Resonance Imaging (MRI) Compared to Unenhanced MRI by Blinded Reader 1 (BR1) — 0.94; 2.21; 2.03; 2.70 scores on a scale — p=< 0.0001

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Gadobutrol (Gadavist, Gadovist, BAY86-4875) (Drug); Gadoteridol (ProHance) (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Bayer
Primary completion
Apr 2009

Outcome Measures

OutcomeResultp-value
PRIMARY
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced Magnetic Resonance Imaging (MRI) Compared to Unenhanced MRI by Blinded Reader 1 (BR1)
0.94; 2.21; 2.03; 2.70; 1.16; 1.78 < 0.0001 sig
PRIMARY
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced Magnetic Resonance Imaging (MRI) Compared to Unenhanced MRI by Blinded Reader 2 (BR2)
1.01; 2.60; 2.19; 2.91; 1.46; 2.28 < 0.0001 sig
PRIMARY
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced Magnetic Resonance Imaging (MRI) Compared to Unenhanced MRI by Blinded Reader 3 (BR3)
0.96; 2.02; 1.73; 2.16; 1.34; 1.76 < 0.0001 sig
PRIMARY
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced Magnetic Resonance Imaging (MRI) Compared to Unenhanced MRI by Average Reader (AR)
0.97; 2.26; 1.98; 2.58; 1.32; 1.93 < 0.0001 sig
PRIMARY
Number of Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Readers
7.41; 7.80; 10.07; 9.63; 6.75; 7.31
PRIMARY
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 1 (BR1)
1.00; 2.62; 2.14; 2.95; 1.26; 2.03 < 0.0001 sig
PRIMARY
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 2 (BR2)
1.15; 3.28; 2.36; 3.22; 1.44; 2.54 < 0.0001 sig
PRIMARY
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 3 (BR3)
1.04; 2.39; 1.75; 2.25; 1.42; 1.85 < 0.0001 sig
PRIMARY
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Average Reader (AR)
1.06; 2.76; 2.09; 2.81; 1.38; 2.14 < 0.0001 sig
PRIMARY
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 1 (BR1)
0.86; 1.69; 1.89; 2.40; 1.04; 1.48 < 0.0001 sig
PRIMARY
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 2 (BR2)
0.87; 1.75; 1.97; 2.51; 1.47; 1.95 < 0.0001 sig
PRIMARY
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 3 (BR3)
0.86; 1.55; 1.72; 2.05; 1.26; 1.64 < 0.0001 sig
PRIMARY
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Average Reader (AR)
0.85; 1.62; 1.82; 2.26; 1.23; 1.65 < 0.0001 sig
SECONDARY
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Average Reader
0.98; 2.22; 1.99; 2.55; 1.32; 1.90 < 0.0001 sig
SECONDARY
Number of Lesions for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Average Reader
8.08; 8.24
SECONDARY
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Average Reader
2.28; 2.24; 2.60; 2.56; 1.94; 1.91
SECONDARY
Number of Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Average Reader
8.25; 8.24
SECONDARY
Percentage of Participants With More Lesions Detected for Combined Unenhanced/Gadobutrol-enhanced MRI or for Unenhanced MRI by Blinded Readers
26.5; 34.8; 35.4; 34.5; 24.4; 40.2
SECONDARY
Percentage of Participants With More Lesions Detected for Combined Unenhanced/Gadoteridol-enhanced MRI or for Unenhanced MRI by Average Reader
37.8; 41.4
SECONDARY
Percentage of Participants With More Lesions Detected for Combined Unenhanced/Gadobutrol-enhanced MRI or for Combined Unenhanced/Gadoteridol-enhanced MRI by Average Reader
41.7; 33.3
SECONDARY
Scores for Two Visualization Parameters (Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator
2.16; 2.90; 1.77; 2.38 < 0.0001 sig
SECONDARY
Number of Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator
3.46; 3.75
SECONDARY
Scores for Two Visualization Parameters (Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator
2.13; 2.90; 1.76; 2.40 < 0.0001 sig
SECONDARY
Scores for Two Visualization Parameters (Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator
2.20; 2.94; 1.80; 2.36 < 0.0001 sig
SECONDARY
Scores for Two Visualization Parameters (Border Delineation and Internal Morphology) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator
2.17; 2.88; 1.78; 2.36 < 0.0001 sig
SECONDARY
Number of Lesions for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator
3.46; 3.74
SECONDARY
Scores for Two Visualization Parameters (Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator
2.13; 2.91; 1.76; 2.39 < 0.0001 sig
SECONDARY
Scores for Two Visualization Parameters (Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator
2.23; 2.88; 1.83; 2.34 < 0.0001 sig
SECONDARY
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical Investigator
2.67; 2.60; 2.95; 2.91; 2.42; 2.39
SECONDARY
Number of Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical Investigator
3.75; 3.74
SECONDARY
Scores for Contrast Enhancement, Border Delineation and Internal Morphology for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical Investigator
2.88; 2.85; 2.90; 2.91; 2.40; 2.39
SECONDARY
Scores for Contrast Enhancement, Border Delineation and Internal Morphology for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical Investigator
2.44; 2.34; 3.04; 2.94; 2.44; 2.39
SECONDARY
Percentage (Per.) of the Exact Diagnostic Matches (Accuracy of Diagnosis) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader
58.2; 64.4 0.0082 sig
SECONDARY
Percentage (Per.) of the Exact Diagnostic Matches (Accuracy of Diagnosis) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator
69.2; 79.1 < 0.0001 sig
SECONDARY
Percentage (Per.) of the Exact Diagnostic Matches (Accuracy of Diagnosis) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Majority Reader
58.9; 65.8 0.0039 sig
SECONDARY
Percentage (Per.) of the Exact Diagnostic Matches (Accuracy of Diagnosis) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator
69.2; 78.4 < 0.0001 sig
SECONDARY
Percentage (Per.) of the Exact Diagnostic Matches (Accuracy of Diagnosis) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Majority Reader
65.1; 65.5
SECONDARY
Percentage (Per.) of the Exact Diagnostic Matches (Accuracy of Diagnosis) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical Investigator
79.1; 78.4
SECONDARY
Accuracy of Detection of Normal/Abnormal Brain Tissue for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader Using T1-weighted (T1w) Images
66.7; 77.2 0.0002 sig
SECONDARY
Sensitivity of Detection of Normal/Abnormal Brain Tissue for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader Using T1-weighted (T1w) Images
62.6; 76.2 < 0.0001 sig
SECONDARY
Specificity of Detection of Normal/Abnormal Brain Tissue for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader Using T1-weighted (T1w) Images
80.3; 80.3 1.0000
SECONDARY
Accuracy of Detection of Normal/Abnormal Brain Tissue for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Majority Reader Using T1-weighted (T1w) Images
66.7; 77.2 0.0002 sig
SECONDARY
Sensitivity of Detection of Normal/Abnormal Brain Tissue for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Majority Reader Using T1-weighted (T1w) Images
62.6; 75.7 0.0001 sig
SECONDARY
Specificity of Detection of Normal/Abnormal Brain Tissue for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Majority Reader Using T1-weighted (T1w) Images
80.3; 82.0 0.7630
SECONDARY
Accuracy of Detection of Normal/Abnormal Brain Tissue for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Majority Reader Using T1-weighted (T1w) Images
77.2; 77.2
SECONDARY
Sensitivity of Detection of Normal/Abnormal Brain Tissue for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Majority Reader Using T1-weighted (T1w) Images
76.2; 75.7
SECONDARY
Specificity of Detection of Normal/Abnormal Brain Tissue for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Majority Reader Using T1-weighted (T1w) Images
80.3; 82.0
SECONDARY
Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader
81.2; 87.7 0.0006 sig
SECONDARY
Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader
47.3; 66.7 0.0004 sig
SECONDARY
Specificity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader
97.0; 97.5 0.6547
SECONDARY
Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator
87.3; 95.2 < 0.0001 sig
SECONDARY
Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator
66.7; 88.2 < 0.0001 sig
SECONDARY
Specificity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator
97.0; 98.5 0.0833
SECONDARY
Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Majority Reader
81.2; 85.6 0.0236 sig
SECONDARY
Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Majority Reader
47.3; 60.2 0.0186 sig
SECONDARY
Specificity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Majority Reader
97.0; 97.5 0.7055
SECONDARY
Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator
87.3; 94.5 < 0.0001 sig
SECONDARY
Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator
66.7; 87.1 < 0.0001 sig
SECONDARY
Specificity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator
97.0; 98.0 0.1573
SECONDARY
Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Majority Reader
87.7; 85.6
SECONDARY
Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Majority Reader
66.7; 60.2
SECONDARY
Specificity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Majority Reader
97.5; 97.5
SECONDARY
Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical Investigator
95.2; 94.5
SECONDARY
Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical Investigator
88.2; 87.1
SECONDARY
Specificity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical Investigator
98.5; 98.0
SECONDARY
Diagnostic Confidence for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Average Reader
2.23; 2.80 < 0.0001 sig
SECONDARY
Diagnostic Confidence for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Average Reader
2.23; 2.80 < 0.0001 sig
SECONDARY
Diagnostic Confidence for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Average Reader
2.80; 2.80
SECONDARY
Diagnostic Confidence for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator
2.59; 3.35 < 0.0001 sig
SECONDARY
Diagnostic Confidence for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator
2.59; 3.31 < 0.0001 sig
SECONDARY
Diagnostic Confidence for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical Investigator
3.35; 3.31
SECONDARY
Comparison of Image Quality Between Gadobutrol and Gadoteridol by Blinded Readers
0.33; 0.38; 0.53 < 0.0001 sig
SECONDARY
Percentage of Participants for Which Blinded Readers Said Image Quality Was Higher
36.0; 7.5; 35.1; 7.5; 62.2; 24.4
SECONDARY
Assessment of the Number of Contrast-enhanced Lesions for Gadobutrol and Gadoteridol by Blinded Readers
1.73; 1.73
SECONDARY
Percentage of Lesion Enhancement From Unenhanced to Combined Unenhanced/Enhanced for Gadobutrol and Gadoteridol by Blinded Readers
80.1; 77.7

Summary

This study involves the use of Magnetic Resonance Imaging (MRI) contrast agents called gadobutrol (Gadavist) Injection and ProHance Injection. The purpose of this study is to look at the safety (what are the side effects) and efficacy (how well does it work) of gadobutrol when used for taking MR images of the brain and spine. The results of the MRI with gadobutrol Injection will be compared to the results of MR images taken without contrast and with the results of the MR images taken with ProHance.

Eligibility Criteria

Inclusion Criteria

  • Is at least 18 years of age
  • Is referred for a contrast-enhanced MRI of the CNS based on current clinical symptoms or results of a previous imaging procedure
  • Has been fully informed about the study, including provisions of the Health Insurance Portability and Accountability Act (HIPAA) as applicable, and has consented to participate

Exclusion Criteria

  • Has any contraindication to the MRI examinations or the use of Gd-containing contrast agents
  • Has a history of severe allergic or anaphylactoid reaction to any allergen including drugs and contrast agents
  • Has severe cardiovascular disease (eg, known long QT syndrome, acute myocardial infarction [< 14 days], unstable angina, congestive heart failure New York Heart Association class IV) or acute stroke (< 48 hours)- Patients with acute renal insufficiency of any severity due to hepato-renal syndrome or in the perioperative liver transplantation period
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00709852). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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