Clinical trial NCT00862459: Dose Finding Study of Gadavist in Central Nervous System (CNS) Magnetic Resonance Imaging (MRI)
Official title: Multi-center, Double-blind, Randomized, Controlled, Parallel Group, Dose Comparison Study With Corresponding Blinded Image Evaluation Following a Single Intravenous Injection of Three Different Doses of Gadobutrol 1.0 Molar (Gadavist) in Patients With Known or Suspected Focal Blood Brain Barrier Disturbances and/or Abnormal Vascularity of the Central Nervous System
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain Diseases
Spinal Cord Diseases
Keywords: Contrast Agents
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2009-03-17
Enrollment: 237
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief 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.

Detailed description: Safety issues are addressed in the Adverse Events section

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.

Primary outcomes:
measure: Categorical Visualization Score (CVS)
timeFrame: up to 2 hours after the injection of study medication
measure: Difference in Number of Lesions Detected in Pre-contrast and Combined Pre-/Post-contrast MRI.
timeFrame: up to 2 hours after the injection of study medication
measure: Assessment of Lesion Contrast Enhancement
timeFrame: up to 2 hours after the injection of study medication
measure: Assessment of Border Delineation
timeFrame: up to 2 hours after the injection of study medication
measure: Assessment of Internal Morphology
timeFrame: up to 2 hours after the injection of study medication
measure: Contrast to Noise Ratio (CNR) Between White and Gray Matter With Gadobutrol Perfusion MRI
timeFrame: up to 2 hours after the injection of study medication
Secondary outcomes:
measure: Accuracy Comparison of Gadobutrol Doses - Detection of Matched Lesions: Blinded Reader 1
timeFrame: up to 2 hours after the injection of study medication
measure: Accuracy Comparison of Gadobutrol Doses - Detection of Matched Lesions: Blinded Reader 2
timeFrame: up to 2 hours after the injection of study medication
measure: Accuracy Comparison of Gadobutrol Doses - Detection of Matched Lesions: Blinded Reader 3
timeFrame: up to 2 hours after the injection of study medication
measure: Accuracy Comparison of Gadobutrol Doses - Detection of Matched Enhanced Lesions: Blinded Reader 1
timeFrame: up to 2 hours after the injection of study medication
measure: Accuracy Comparison of Gadobutrol Doses - Detection of Matched Enhanced Lesions: Blinded Reader 2
timeFrame: up to 2 hours after the injection of study medication
measure: Accuracy Comparison of Gadobutrol Doses - Detection of Matched Enhanced Lesions: Blinded Reader 3
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of the Correct Diagnosis Following Gadobutrol-enhanced and Unenhanced MRI
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of the Diagnostic Confidence Based on Unenhanced MRI and Combined Unenhanced and Enhanced MRI
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Quality (Uncorrected Cerebral Blood Volume [CBV]) - Blinded Reader 1
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Quality (Uncorrected Cerebral Blood Volume (CBV)) - Blinded Reader 2
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Quality (Uncorrected Cerebral Blood Volume (CBV)) - Blinded Reader 3
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Quality (Corrected Cerebral Blood Volume (CBV)) - Blinded Reader 1
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Quality (Corrected Cerebral Blood Volume (CBV)) - Blinded Reader 2
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Quality (Corrected Cerebral Blood Volume (CBV)) - Blinded Reader 3
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Quality (Cerebral Blood Flow (CBF)) - Blinded Reader 1
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Quality (Cerebral Blood Flow (CBF)) - Blinded Reader 2
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Quality (Cerebral Blood Flow (CBF)) - Blinded Reader 3
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Quality (Time to Peak (TTP)) - Blinded Reader 1
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Quality (Time to Peak (TTP)) - Blinded Reader 2
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Quality (Time to Peak (TTP)) - Blinded Reader 3
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Quality (Mean Transit Time (MTT)) - Blinded Reader 1
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Quality (Mean Transit Time (MTT)) - Blinded Reader 2
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Quality (Mean Transit Time (MTT)) - Blinded Reader 3
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Quality (Permeability Factor (PF) - Blinded Reader 1
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Quality (Permeability Factor (PF) - Blinded Reader 2
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Quality (Permeability Factor (PF)) - Blinded Reader 3
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Parameter Value (Uncorrected Cerebral Blood Volume (CBV)) - Independent Radiologist
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Parameter Value (Corrected Cerebral Blood Volume (CBV)) - Independent Radiologist
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Parameter Value (Cerebral Blood Flow (CBF)) - Independent Radiologist
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Parameter Value (Time to Peak (TTP)) - Independent Radiologist
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Parameter Value (Mean Transit Time (MTT)) - Independent Radiologist
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Parameter Value (Permeability Factor (PF)) - Independent Radiologist
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Artifacts (Uncorrected Cerebral Blood Volume (CBV)) - Blinded Reader
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Artifacts (Corrected Cerebral Blood Volume (CBV)) - Blinded Reader
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Artifacts (Cerebral Blood Flow (CBF)) - Blinded Reader
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Artifacts (Time to Peak (TTP)) - Blinded Reader
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Artifacts (Mean Transit Time (MTT)) - Blinded Reader
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of Perfusion Map Artifacts (Permeability Factor (PF)) - Blinded Reader
timeFrame: up to 2 hours after the injection of study medication
measure: Evaluation of MRI Tumor Grade Agreement With Biopsy Results by Dose Group
timeFrame: up to 2 hours after the injection of study medication
measure: Contrast to Noise Ratio (CNR) of Lesion/Gray Matter and Lesion/White Matter
timeFrame: up to 2 hours after the injection of study medication
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: San Diego
country: United States
facility: University of California-San Diego Medical Center
state: California
city: Jacksonville
country: United States
facility: Shands Jacksonville Medical Center
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Neuroscience Institute
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Methodist Hospital
state: Nebraska
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Health System
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: Methodist Le Bonheur Healthcare
state: Tennessee
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin - Madison
state: Wisconsin
city: Lornas de Zamora
country: Argentina
facility: Fundacion Cientifica del Sur
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: TCba Salguero
city: Sao Paulo
country: Brazil
facility: Hospital da Beneficiência Portuguesa
city: Medellín
country: Colombia
facility: Centro de Diagnostico Medico
state: Antioquia
city: Medellín
country: Colombia
facility: Fundación Instituto de Alta tecnología médica de Antioquia
state: Antioquia
city: Cali
country: Colombia
facility: DIME Clinica Neurocardiovascular S.A.
state: Valle del Cauca
city: Cali
country: Colombia
facility: Fundación Clínica Valle del Lili
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Breuer J, Gutierrez J, Latchaw R, Lehr R, Sorensen AG. Gadobutrol in the central nervous system at three doses: results from a phase II, randomized, multicenter trial. J Magn Reson Imaging. 2014 Feb;39(2):410-8. doi: 10.1002/jmri.24180. Epub 2013 May 16.