Phase 2
N=237
Dose Finding Study of Gadavist in Central Nervous System (CNS) Magnetic Resonance Imaging (MRI)
Brain Diseases · Spinal Cord Diseases
Bottom Line
View on ClinicalTrials.gov: NCT00862459 ↗Enrolled (actual)
237
Serious AEs
0.4%
Results posted
Jan 2012
Primary outcome: Primary: Categorical Visualization Score (CVS) — 1.43; 2.02; 1.98 Scores on a scale — p=0.003
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Gadobutrol~0.03 mmol/kg BW (Gadavist, Gadovist, BAY86-4875) (Drug); Gadobutrol~0.1 mmol/kg BW (Gadavist, Gadovist, BAY86-4875) (Drug); Gadobutrol~0.3 mmol/kg BW (Gadavist, Gadovist, BAY86-4875) (Drug); OptiMARK~0.1 mmol/kg BW (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Bayer
- Primary completion
- Mar 2007
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Categorical Visualization Score (CVS) |
1.43; 2.02; 1.98 | 0.003 sig |
| PRIMARY Difference in Number of Lesions Detected in Pre-contrast and Combined Pre-/Post-contrast MRI. |
-0.03; 0.04; 0.09 | — |
| PRIMARY Assessment of Lesion Contrast Enhancement |
0.98; 1.78; 1.79 | — |
| PRIMARY Assessment of Border Delineation |
0.28; 0.68; 0.70 | — |
| PRIMARY Assessment of Internal Morphology |
0.52; 0.90; 0.80 | — |
| PRIMARY Contrast to Noise Ratio (CNR) Between White and Gray Matter With Gadobutrol Perfusion MRI |
9.42; 27.0; 22.2 | — |
| SECONDARY Accuracy Comparison of Gadobutrol Doses - Detection of Matched Lesions: Blinded Reader 1 |
63.58; 65.24; 54.49 | 0.80 |
| SECONDARY Accuracy Comparison of Gadobutrol Doses - Detection of Matched Lesions: Blinded Reader 2 |
57.62; 71.05; 57.47 | 0.03 sig |
| SECONDARY Accuracy Comparison of Gadobutrol Doses - Detection of Matched Lesions: Blinded Reader 3 |
63.31; 57.18; 50.05 | 0.11 |
| SECONDARY Accuracy Comparison of Gadobutrol Doses - Detection of Matched Enhanced Lesions: Blinded Reader 1 |
48.10; 72.73; 55.21 | 0.02 sig |
| SECONDARY Accuracy Comparison of Gadobutrol Doses - Detection of Matched Enhanced Lesions: Blinded Reader 2 |
69.23; 82.14; 63.77 | 0.07 |
| SECONDARY Accuracy Comparison of Gadobutrol Doses - Detection of Matched Enhanced Lesions: Blinded Reader 3 |
55.07; 73.53; 68.24 | 0.02 sig |
| SECONDARY Evaluation of the Correct Diagnosis Following Gadobutrol-enhanced and Unenhanced MRI |
62.3; 57.1; 54.2; 37.7; 42.9; 45.8 | — |
| SECONDARY Evaluation of the Diagnostic Confidence Based on Unenhanced MRI and Combined Unenhanced and Enhanced MRI |
3.3; 3.6; 3.6; 23.0; 28.6; 23.2 | — |
| SECONDARY Evaluation of Perfusion Map Quality (Uncorrected Cerebral Blood Volume [CBV]) - Blinded Reader 1 |
8.2; 7.1; 3.6; 1.6; 0; 0 | — |
| SECONDARY Evaluation of Perfusion Map Quality (Uncorrected Cerebral Blood Volume (CBV)) - Blinded Reader 2 |
9.8; 10.7; 10.7; 1.6; 0; 0 | — |
| SECONDARY Evaluation of Perfusion Map Quality (Uncorrected Cerebral Blood Volume (CBV)) - Blinded Reader 3 |
11.5; 8.9; 16.1; 1.6; 0; 0 | — |
| SECONDARY Evaluation of Perfusion Map Quality (Corrected Cerebral Blood Volume (CBV)) - Blinded Reader 1 |
8.2; 10.7; 3.6; 1.6; 0; 0 | — |
| SECONDARY Evaluation of Perfusion Map Quality (Corrected Cerebral Blood Volume (CBV)) - Blinded Reader 2 |
11.5; 16.1; 7.1; 1.6; 0; 0 | — |
| SECONDARY Evaluation of Perfusion Map Quality (Corrected Cerebral Blood Volume (CBV)) - Blinded Reader 3 |
11.5; 12.5; 17.9; 1.6; 1.8; 0 | — |
| SECONDARY Evaluation of Perfusion Map Quality (Cerebral Blood Flow (CBF)) - Blinded Reader 1 |
6.6; 12.5; 1.8; 1.6; 0; 0 | — |
| SECONDARY Evaluation of Perfusion Map Quality (Cerebral Blood Flow (CBF)) - Blinded Reader 2 |
8.2; 12.5; 8.9; 1.6; 0; 0 | — |
| SECONDARY Evaluation of Perfusion Map Quality (Cerebral Blood Flow (CBF)) - Blinded Reader 3 |
13.1; 10.7; 16.1; 1.6; 1.8; 0 | — |
| SECONDARY Evaluation of Perfusion Map Quality (Time to Peak (TTP)) - Blinded Reader 1 |
6.6; 8.9; 5.4; 1.6; 1.8; 0 | — |
| SECONDARY Evaluation of Perfusion Map Quality (Time to Peak (TTP)) - Blinded Reader 2 |
24.6; 17.9; 8.9; 1.6; 0; 0 | — |
| SECONDARY Evaluation of Perfusion Map Quality (Time to Peak (TTP)) - Blinded Reader 3 |
11.5; 10.7; 17.9; 1.6; 1.8; 0 | — |
| SECONDARY Evaluation of Perfusion Map Quality (Mean Transit Time (MTT)) - Blinded Reader 1 |
8.2; 7.1; 3.6; 1.6; 0; 0 | — |
| SECONDARY Evaluation of Perfusion Map Quality (Mean Transit Time (MTT)) - Blinded Reader 2 |
13.1; 16.1; 12.5; 1.6; 0; 0 | — |
| SECONDARY Evaluation of Perfusion Map Quality (Mean Transit Time (MTT)) - Blinded Reader 3 |
11.5; 12.5; 16.1; 1.6; 1.8; 0 | — |
| SECONDARY Evaluation of Perfusion Map Quality (Permeability Factor (PF) - Blinded Reader 1 |
13.1; 8.9; 1.8; 11.5; 21.4; 28.6 | — |
| SECONDARY Evaluation of Perfusion Map Quality (Permeability Factor (PF) - Blinded Reader 2 |
14.8; 16.1; 8.9; 3.3; 0; 0 | — |
| SECONDARY Evaluation of Perfusion Map Quality (Permeability Factor (PF)) - Blinded Reader 3 |
11.5; 10.7; 19.6; 4.9; 3.6; 0 | — |
| SECONDARY Evaluation of Perfusion Map Parameter Value (Uncorrected Cerebral Blood Volume (CBV)) - Independent Radiologist |
114.61; 346.81; 1209.89 | — |
| SECONDARY Evaluation of Perfusion Map Parameter Value (Corrected Cerebral Blood Volume (CBV)) - Independent Radiologist |
2728.71; 2682.97; 3382.20 | — |
| SECONDARY Evaluation of Perfusion Map Parameter Value (Cerebral Blood Flow (CBF)) - Independent Radiologist |
4.80; 5.15; 3.48 | — |
| SECONDARY Evaluation of Perfusion Map Parameter Value (Time to Peak (TTP)) - Independent Radiologist |
79.39; 80.31; 86.52 | — |
| SECONDARY Evaluation of Perfusion Map Parameter Value (Mean Transit Time (MTT)) - Independent Radiologist |
6.30; 6.02; 7.05 | — |
| SECONDARY Evaluation of Perfusion Map Parameter Value (Permeability Factor (PF)) - Independent Radiologist |
4.04; 1.65; 0.99 | — |
| SECONDARY Evaluation of Perfusion Map Artifacts (Uncorrected Cerebral Blood Volume (CBV)) - Blinded Reader |
1.6; 0; 0; 72.1; 75; 69.6 | — |
| SECONDARY Evaluation of Perfusion Map Artifacts (Corrected Cerebral Blood Volume (CBV)) - Blinded Reader |
1.6; 0; 0; 75.4; 76.8; 66.1 | — |
| SECONDARY Evaluation of Perfusion Map Artifacts (Cerebral Blood Flow (CBF)) - Blinded Reader |
1.6; 0; 0; 70.5; 85.7; 71.4 | — |
| SECONDARY Evaluation of Perfusion Map Artifacts (Time to Peak (TTP)) - Blinded Reader |
1.6; 1.8; 0; 75.4; 76.8; 75 | — |
| SECONDARY Evaluation of Perfusion Map Artifacts (Mean Transit Time (MTT)) - Blinded Reader |
1.6; 0; 0; 80.3; 67.9; 71.4 | — |
| SECONDARY Evaluation of Perfusion Map Artifacts (Permeability Factor (PF)) - Blinded Reader |
73.8; 75; 71.4; 21.3; 23.2; 26.8 | — |
| SECONDARY Evaluation of MRI Tumor Grade Agreement With Biopsy Results by Dose Group |
60.0; 57.1; 40.0; 40.0; 42.9; 40.0 | — |
| SECONDARY Contrast to Noise Ratio (CNR) of Lesion/Gray Matter and Lesion/White Matter |
-0.03; 13.0; 5.38; -10; -17; -17 | — |
Summary
The purpose of this study is to look at the safety (what are the side effects) and efficacy (how well does it work) of Gadavist when used for taking images of the brain and spine. The results of the MRI with Gadavist Injection will be compared to the results of MR images taken without contrast and with the results of the MR images taken with OptiMARK.
Eligibility Criteria
Inclusion Criteria
- Patients with either known or highly suspected focal areas of disruption of the blood brain barrier (BBB) (eg, primary and secondary tumors, focal inflammatory or demyelinating disorders) and/or abnormal vascularity in the CNS, who are scheduled to undergo a routine contrast-enhanced MRI of the CNS.
- Patients with untreated brain tumors should constitute a minimum of 50% of the study population and patients with treated brain tumors will be limited to a maximum of 20% of the study population
Exclusion Criteria
- Is a female patient who is pregnant or nursing.
- Is a female of childbearing potential and did not have a negative urine pregnancy test the same day as the administration of gadobutrol or comparator treatment.
- Has received any investigational product within 30 days prior to enrolling in this study.
- Has been previously enrolled in this study or any other study using gadobutrol.
- Has any contraindication to the MRI examinations.
- Has a history of severe allergic or anaphylactoid reaction to any allergen including drugs and contrast agents.
- Has received any contrast agent within 24 hours prior to gadobutrol contrast administration, or is scheduled to receive any contrast agent within 72 hours after the gadobutrol study.
- Is considered to be clinically unstable or his/her clinical course during the study period is unpredictable (eg, due to previous surgery, acute renal failure).
- Has been treated with high dose (>55 cobalt Gy equivalent) photon radiation or global radiotherapy for CNS lesions at any time before entering the study.
- Is scheduled to receive chemotherapy or radiotherapy during the study period.
- Is expected or scheduled to have a change in any treatment or procedure between the comparator and gadobutrol MRIs that may alter their interpretation.
- Is scheduled or is likely to require a biopsy or surgery within the 72 hours after the gadobutrol MRI procedure, or is scheduled for or has undergone such interventions between the comparator and gadobutrol studies.
- Has severe cardiovascular disease.
- Has any contraindication to OptiMARK according to the package insert.
- Has more than 30 brain lesions detected by any prior imaging examination.
Data sourced from ClinicalTrials.gov (NCT00862459). 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.