Dose Finding Study of Gadavist in Central Nervous System (CNS) Magnetic Resonance Imaging (MRI)

NCT00862459 | Completed Phase 2 Results

• 2 other identifiers: 91400308200
• Study Type: interventional
• Target: 237
• Locations: 4 countries
• Sites: 27

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.

Conditions

Brain Diseases; Spinal Cord Diseases

Keywords

Contrast Agents

Outcome Measures

Primary Outcomes (6)

• Categorical Visualization Score (CVS)

  The primary visualization variables (number \[no.\] of lesions detected, border delineation, contrast enhancement, internal morphology) were condensed to a composite score (CVS). Each variable was considered a category; the CVS was calculated as: CVS=(No. of categories with increase over precontrast)-(No. of categories with decrease over precontrast). The possible outcomes of the CVS for a participant and each reader were in the range of - 3 to +4. The CVS was averaged across the 3 blinded readers, producing 1 mean CVS per participant. The higher the CVS, the more effective the treatment.

  up to 2 hours after the injection of study medication

• Difference in Number of Lesions Detected in Pre-contrast and Combined Pre-/Post-contrast MRI.

  Three blinded readers evaluated the unenhanced MRI sets and the combined unenhanced/gadobutrol-enhanced MRI sets to evaluate the number of lesions, which was then averaged to produce an average reader value.

  up to 2 hours after the injection of study medication

• Assessment of Lesion Contrast Enhancement

  The blinded readers assessed the degree of contrast enhancement for each lesion on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement, which was then averaged to produce an average reader score.

  up to 2 hours after the injection of study medication

• Assessment of Border Delineation

  The blinded readers assessed the delineation for each lesion on a 4-point scale where 1 = none and 4 = excellent, which was then averaged to produce an average reader score.

  up to 2 hours after the injection of study medication

• Assessment of Internal Morphology

  The blinded readers assessed the degree of information available about internal morphology and structure for each lesion on a 3-point scale where 1 = poor and 3 = good, which was then averaged to produce an average reader score.

  up to 2 hours after the injection of study medication

• Contrast to Noise Ratio (CNR) Between White and Gray Matter With Gadobutrol Perfusion MRI

  CNR between white and gray matter in the perfusion imaging was defined as the signal intensity (SI) difference between white and gray matter divided by the standard deviation of the SI of white matter. An independent radiologist evaluated the gadobutrol-enhanced perfusion MRI for signal intensity.

  up to 2 hours after the injection of study medication

Secondary Outcomes (40)

• Accuracy Comparison of Gadobutrol Doses - Detection of Matched Lesions: Blinded Reader 1

  up to 2 hours after the injection of study medication

• Accuracy Comparison of Gadobutrol Doses - Detection of Matched Lesions: Blinded Reader 2

  up to 2 hours after the injection of study medication

• Accuracy Comparison of Gadobutrol Doses - Detection of Matched Lesions: Blinded Reader 3

  up to 2 hours after the injection of study medication

• Accuracy Comparison of Gadobutrol Doses - Detection of Matched Enhanced Lesions: Blinded Reader 1

  up to 2 hours after the injection of study medication

• Accuracy Comparison of Gadobutrol Doses - Detection of Matched Enhanced Lesions: Blinded Reader 2

  up to 2 hours after the injection of study medication

Study Arms (3)

Gadobutrol~0.03 mmol/kg BW (Gadavist, BAY86-4875)

EXPERIMENTAL

Participant received one dose of 0.03 mmol/kg BW of Gadobutrol and one dose of 0.1 mmol/kg body weight (BW) of OptiMARK. The order in which the participants received Gadobutrol and OptiMARK was randomized. Gadobutrol was administered via a power injector at a rate of 5 mL/s followed by a 20 mL 0.9% saline flush at the same rate.

Drug: Gadobutrol~0.03 mmol/kg BW (Gadavist, Gadovist, BAY86-4875); Drug: OptiMARK~0.1 mmol/kg BW

Gadobutrol~0.1 mmol/kg BW (Gadavist, BAY86-4875)

EXPERIMENTAL

Participant received one dose of 0.1 mmol/kg BW of Gadobutrol and one dose of 0.1 mmol/kg BW of OptiMARK. The order in which the participants received Gadobutrol and OptiMARK was randomized. Gadobutrol was administered via a power injector at a rate of 5 mL/s followed by a 20 mL 0.9% saline flush at the same rate.

Drug: Gadobutrol~0.1 mmol/kg BW (Gadavist, Gadovist, BAY86-4875); Drug: OptiMARK~0.1 mmol/kg BW

Gadobutrol~0.3 mmol/kg BW (Gadavist, BAY86-4875)

EXPERIMENTAL

Participant received one dose of 0.3 mmol/kg BW of Gadobutrol and one dose of 0.1 mmol/kg BW of OptiMARK. The order in which the participants received Gadobutrol and OptiMARK was randomized. Gadobutrol was administered via a power injector at a rate of 5 mL/s followed by a 20 mL 0.9% saline flush at the same rate.

Drug: Gadobutrol~0.3 mmol/kg BW (Gadavist, Gadovist, BAY86-4875); Drug: OptiMARK~0.1 mmol/kg BW

Interventions

Gadobutrol~0.03 mmol/kg BW (Gadavist, Gadovist, BAY86-4875) DRUG

Participant received one dose of 0.03 mmol/kg BW of Gadobutrol. Gadobutrol was administered via a power injector at a rate of 5 mL/s followed by a 20 mL 0.9% saline flush at the same rate.

Gadobutrol~0.03 mmol/kg BW (Gadavist, BAY86-4875)

Gadobutrol~0.1 mmol/kg BW (Gadavist, Gadovist, BAY86-4875) DRUG

Participant received one dose of 0.1 mmol/kg BW of Gadobutrol. Gadobutrol was administered via a power injector at a rate of 5 mL/s followed by a 20 mL 0.9% saline flush at the same rate.

Gadobutrol~0.1 mmol/kg BW (Gadavist, BAY86-4875)

Gadobutrol~0.3 mmol/kg BW (Gadavist, Gadovist, BAY86-4875) DRUG

Participant received one dose of 0.3 mmol/kg BW of Gadobutrol. Gadobutrol was administered via a power injector at a rate of 5 mL/s followed by a 20 mL 0.9% saline flush at the same rate.

Gadobutrol~0.3 mmol/kg BW (Gadavist, BAY86-4875)

OptiMARK~0.1 mmol/kg BW DRUG

Participant received one dose of 0.1 mmol/kg BW of OptiMARK. OptiMARK was administered via a power injector at a rate of 2 mL/s followed by a 20 mL 0.9% saline flush at the same rate.

Gadobutrol~0.03 mmol/kg BW (Gadavist, BAY86-4875); Gadobutrol~0.1 mmol/kg BW (Gadavist, BAY86-4875); Gadobutrol~0.3 mmol/kg BW (Gadavist, BAY86-4875)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bayer: lead

Study Sites (27)

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

University of California-San Diego Medical Center

San Diego, California, 92103, United States

Location

Shands Jacksonville Medical Center

Jacksonville, Florida, 32209, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Indiana Neuroscience Institute

Indianapolis, Indiana, 46260, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19146, United States

Location

University of Pittsburgh Medical Center Health System

Pittsburgh, Pennsylvania, 15213, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Methodist Le Bonheur Healthcare

Memphis, Tennessee, 38104, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

University of Wisconsin - Madison

Madison, Wisconsin, 53792, United States

Location

TCba Salguero

Buenos Aires, Buenos Aires, Argentina

Location

Fundacion Cientifica del Sur

Lornas de Zamora, Buenos Aires, B1832BQS, Argentina

Location

Hospital da Beneficiência Portuguesa

São Paulo, São Paulo, 01323-001, Brazil

Location

Centro de Diagnostico Medico

Medellín, Antioquia, Colombia

Location

Fundación Instituto de Alta tecnología médica de Antioquia

Medellín, Antioquia, Colombia

Location

DIME Clinica Neurocardiovascular S.A.

Cali, Valle del Cauca Department, Colombia

Location

Fundación Clínica Valle del Lili

Cali, Colombia

Location

Related Publications (1)

• 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.

  PMID: 23681501 DERIVED

MeSH Terms

Conditions

Brain Diseases; Spinal Cord Diseases

Interventions

gadobutrol

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Nervous System Diseases

Limitations and Caveats

OptiMARK was used as a standard of reference in this study. A formal comparison of the efficacy of gadobutrol and OptiMARK was not specified prospectively in the statistical analysis plan. For completeness, the safety data of OptiMARK is presented.

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: BAYER

clinical-trials-contact@bayerhealthcare.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2008
• First Posted: March 17, 2009
• Study Start: August 1, 2005
• Primary Completion: March 1, 2007
• Study Completion: March 1, 2007
• Last Updated: January 13, 2014
• Results First Posted: January 30, 2012

Record last verified: 2013-12

Locations

AR (2); US (20); BR (1); CO (4)