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

NCT00709852 | Completed Phase 3 Results

• 3 other identifiers: 916812007-004746-33310123
• Study Type: interventional
• Target: 402
• Locations: 7 countries
• Sites: 75

Brief 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.

Conditions

Diagnostic Imaging; Central Nervous System Diseases

Keywords

Patients referred for a contrast-enhanced MRI of the CNS; CNS Imaging

Outcome Measures

Primary Outcomes (13)

• 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)

  BR1 evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

  Up to 2 hours after injection of gadobutrol

• 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)

  BR2 evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

  Up to 2 hours after injection of gadobutrol

• 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)

  BR3 evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

  Up to 2 hours after injection of gadobutrol

• 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)

  The AR analysis used the mean of the values for the 3 blinded readers. The 3 BRs evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

  Up to 2 hours after injection of gadobutrol

• Number of Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Readers

  The blinded readers evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another to determine the total number of lesions.

  Up to 2 hours after injection of gadobutrol

• 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)

  BR1 evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

  Up to 2 hours after injection of gadobutrol

• 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)

  BR2 evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

  Up to 2 hours after injection of gadobutrol

• 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)

  BR3 evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

  Up to 2 hours after injection of gadobutrol

• 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)

  The AR analysis used the mean of the values for the 3 blinded readers. The 3 BRs evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

  Up to 2 hours after injection of gadobutrol

• 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)

  BR1 evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

  Up to 2 hours after injection of gadobutrol

• 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)

  BR2 evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

  Up to 2 hours after injection of gadobutrol

• 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)

  BR3 evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

  Up to 2 hours after injection of gadobutrol

• 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)

  The AR analysis used the mean of the values for the 3 blinded readers. The 3 BRs evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

  Up to 2 hours after injection of gadobutrol

Secondary Outcomes (62)

• 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

  Up to 2 hours after injection of gadoteridol

• Number of Lesions for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Average Reader

  Up to 2 hours after injection of gadoteridol

• 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

  Up to 2 hours after injection of gadobutrol or gadoteridol

• Number of Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Average Reader

  Up to 2 hours after injection of gadobutrol or gadoteridol

• Percentage of Participants With More Lesions Detected for Combined Unenhanced/Gadobutrol-enhanced MRI or for Unenhanced MRI by Blinded Readers

  Up to 2 hours after injection of gadobutrol

Study Arms (2)

Gadobutrol then Gadoteridol

EXPERIMENTAL

Participants received a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) in Period 1 and a single dose of gadoteridol at the approved dose, 0.1 mmol/kg bw, via i.v. in Period 2.

Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875); Drug: Gadoteridol (ProHance)

Gadoteridol then Gadobutrol

EXPERIMENTAL

Participants received a single dose of gadoteridol at the approved dose, 0.1 mmol/kg bw, via i.v. in Period 1 and a single dose of gadobutrol 0.1 mmol/kg bw via i.v. in Period 2.

Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875); Drug: Gadoteridol (ProHance)

Interventions

Gadobutrol (Gadavist, Gadovist, BAY86-4875) DRUG

Participants received a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous)

Gadobutrol then Gadoteridol; Gadoteridol then Gadobutrol

Gadoteridol (ProHance) DRUG

Participants received a single dose of gadoteridol at the approved dose, 0.1 mmol/kg bw, via i.v.

Gadobutrol then Gadoteridol; Gadoteridol then Gadobutrol

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (79)

West Alabama Research, Inc.

Birmingham, Alabama, 35209, United States

Location

Achieve Clinical Research, LLC

Tuscaloosa, Alabama, 35406, United States

Location

Los Gatos MRI

Los Gatos, California, 95032, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92658-6100, United States

Location

Redwood Regional Medical Group, Inc.

Santa Rosa, California, 95403, United States

Location

University of Florida - Jacksonville

Jacksonville, Florida, 32209, United States

Location

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, 60201, United States

Location

Atchison Hospital

Atchison, Kansas, 66002, United States

Location

University of Maryland Hospital System

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Hospital/Health System

Baltimore, Maryland, 21287, United States

Location

Shields MRI - Brockton

Brockton, Massachusetts, 02301, United States

Location

VA Boston Healthcare System-West Roxbury Division

West Roxbury, Massachusetts, 02132, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of New Mexico School of Medicine

Albuquerque, New Mexico, 87131, United States

Location

Kingston Neurological Associates, PC

Kingston, New York, 12401, United States

Location

NYU Hospital for Joint Diseases

New York, New York, 10003, United States

Location

Duke University Medical Center

Durham, North Carolina, 27707, United States

Location

The Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, 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

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Aurora Saint Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

St George Hospital

Kogarah, New South Wales, 2217, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Landeskrankenhaus Donauregion Tulln

Tulln, Lower Austria, 3430, Austria

Location

Medizinische Universität Graz

Graz, Styria, 8036, Austria

Location

LNK Wagner Jauregg

Linz, Upper Austria, 4020, Austria

Location

Allgemeines Krankenhaus der Stadt Wien Universitätskliniken

Vienna, Vienna, 1090, Austria

Location

Fundación Instituto de Alta tecnología médica de Antioquia

Medellín, Antioquia, Colombia

Location

Fundación Santa Fe de Bogotá - Hospital Universitario

Bogotá, Cundinamarca, Colombia

Location

DIME Clinica Neurocardiovascular S.A.

Cali, Valle del Cauca Department, Colombia

Location

Centro de Diagnostico Medico

Medellín, Colombia

Location

Deutsches Krebsforschungszentrum

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Städtisches Klinikum Karlsruhe gGmbH

Karlsruhe, Baden-Wurttemberg, 76133, Germany

Location

Klinikum Mannheim gGmbH

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

Zentralklinikum Augsburg

Augsburg, Bavaria, 865156, Germany

Location

Universitätsklinikum Erlangen

Erlangen, Bavaria, 91054, Germany

Location

LMU Klinikum der Universität München - Großhadern

München, Bavaria, 81377, Germany

Location

Klinikum rechts der Isar

München, Bavaria, 81675, Germany

Location

Klinikum Ernst von Bergmann

Potsdam, Brandenburg, 14467, Germany

Location

Universitätsklinikum Hamburg Eppendorf (UKE)

Hamburg, Hamburg, 20246, Germany

Location

Krankenhaus Nordwest

Frankfurt am Main, Hesse, 60488, Germany

Location

Kliniken der Medizinischen Hochschule Hannover

Hanover, Lower Saxony, 30625, Germany

Location

Medizinische Einrichtungen der Universität Bonn

Bonn, North Rhine-Westphalia, 53105, Germany

Location

Universitätsklinikum Köln

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Medizinisches Versorgungszentrum Prof. Dr. D. Uhlenbrock

Dortmund, North Rhine-Westphalia, 44263, Germany

Location

Universitätskliniken des Saarlandes

Homburg, Saarland, 66424, Germany

Location

Medizinische Fakultät Carl Gustav Carus

Dresden, Saxony, 01307, Germany

Location

Universitätsklinikum Leipzig AöR

Leipzig, Saxony, 04103, Germany

Location

Klinikum der Christian-Albrechts-Universität

Kiel, Schleswig-Holstein, 24105, Germany

Location

Universitätsklinikum Charite zu Berlin

Berlin, State of Berlin, 10117, Germany

Location

HELIOS Klinikum Erfurt GmbH

Erfurt, Thuringia, 99089, Germany

Location

CT /MRI centre

Indore, Madhya Pradesh, 252002, India

Location

Piramal Diagnostic- Jankharia Imaging

Mumbai, Maharashtra, 400004, India

Location

Sanjay Gandhi Post Graduate Institute of Medical Sciences

Lucknow, 226 014, India

Location

Bombay Hospital, Institute of Medical sciences

Mumbai, 400020, India

Location

Nagoya Kyoritsu Clinic

Nagoya, Aichi-ken, 454-0933, Japan

Location

Nagoya Kyoritsu Hospital

Nagoya, Aichi-ken, 454-0933, Japan

Location

Social Insurance Chukyo Hospital

Nagoya, Aichi-ken, 457-8510, Japan

Location

Himeji Medical Center

Himeji, Hyōgo, 670-8520, Japan

Location

Himeji Central Hospital

Himeji, Hyōgo, 672-8501, Japan

Location

Institute of Biomedical Research and Innovation

Kobe, Hyōgo, 650-0047, Japan

Location

Kobe City Medical Center General Hospital

Kobe, Hyōgo, 650-0047, Japan

Location

Shinsuma Hospital

Kobe, Hyōgo, 654-0047, Japan

Location

Utano National Hospital

Kyoto, Kyoto, 616-8255, Japan

Location

Kishiwada Tokushukai Hospital

Kishiwada, Osaka, 596-8522, Japan

Location

Osaka Medical Center for Cancer and Cardiovascular Diseases

Osaka, Osaka, 537-8511, Japan

Location

Osaka National Hospital

Osaka, Osaka, 540-0006, Japan

Location

Osaka General Medical Center

Osaka, Osaka, 558-8558, Japan

Location

Shimonoseki Kosei Hospital

Shimonoseki, Yamaguchi, 750-0061, Japan

Location

Universitätsspital Basel

Basel, Canton of Basel-City, 4031, Switzerland

Location

Hôpital Cantonal Universitaire de Genève

Geneva, Canton of Geneva, 1211, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, Canton of St. Gallen, 9007, Switzerland

Location

Inselspital Bern

Bern, 3010, Switzerland

Location

Luzerner Kantonsspital

Lucerne, 6000, Switzerland

Location

Related Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

MeSH Terms

Conditions

Central Nervous System Diseases

Interventions

gadobutrol; gadoteridol

Condition Hierarchy (Ancestors)

Nervous System Diseases

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 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2008
• First Posted: July 3, 2008
• Study Start: June 1, 2008
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2009
• Last Updated: December 30, 2014
• Results First Posted: March 6, 2012

Record last verified: 2014-12

Locations

AU (4); US (24); CO (4); IN (4); DE (20); CH (5); JP (14)