Comparison of Gadovist 75% Standard Dose to Dotarem at Full Standard Dose

NCT03602339 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: 197732018-000690-78
• Study Type: interventional
• Target: 157
• Locations: 7 countries
• Sites: 20

Brief Summary

The study was conducted to gain knowledge about a new dose of a diagnostic drug that is used for contrast-enhanced Magnetic Resonance Imaging (MRI) of the human central nervous system (CNS). MRI can visualize the anatomy of the body and is used to detect medical conditions. Diagnostic drugs like gadobutrol and gadoterate contain an element called gadolinium that is applied to improve the analysability of MRI-images. The purpose of this study was to examine if contrast-enhanced MRI using a reduced dose of the gadolinium-based contrast agent gadobutrol delivers images of similar quality to those obtained when a full dose of the gadolinium-based contrast agent gadoterate was used.

Conditions

Magnetic Resonance Imaging

Keywords

Gadolinium; Contrast enhancement; Central nervous system lesion

Outcome Measures

Primary Outcomes (3)

• Degree of Lesion Contrast Enhancement

  Degree of lesion contrast enhancement is assessed by 3 blinded Readers (Full Analysis Set). Results are presented as the Average Reader score. Blinded Readers scored up to 5 lesions using image sequences and a 4-point scale (1 - No = Lesion not enhanced; 2 - Moderate = Lesion weakly enhanced; 3 - Good = Lesion clearly enhanced; 4 - Excellent = Lesion clearly and brightly enhanced).

  Up to 20 days

• Lesion Border Delineation

  Lesion border delineation is assessed by 3 blinded Readers (Full Analysis Set). Results are presented as the Average Reader score. Blinded readers scored the delineation of up to 5 lesions using image sequences and a 4-point scale (1 - None = No or unclear delineation; 2 - Moderate = Partial delineation; 3 - Good = Almost clear, but incomplete delineation; 4 - Excellent = Clear and complete delineation).

  Up to 20 days

• Lesion Internal Morphology

  Lesion internal morphology is assessed by 3 blinded Readers (Full Analysis Set). Results are presented as the Average Reader score. Blinded Readers scored the structure and internal morphology of up to 5 lesions using image sequences and a 3-point scale (1 - Poor = Poor visibility; 2 - Moderate = Partial visibility; 3 - Good = Sufficient visibility)

  Up to 20 days

Secondary Outcomes (6)

• Number of Lesions Identified

  Up to 20 days

• Detection of Malignant Disease

  Up to 20 days

• Confidence in Diagnosis

  Up to 20 days

• Image Quality

  Up to 20 days

• Contrast Enhancement Utilizing an Exploratory Overall Contrast Enhancement Estimation Algorithm

  Up to 20 days

Study Arms (2)

Arm 1_Suspected CNS-lesion

EXPERIMENTAL

Patients with suspected or confirmed CNS-lesions underwent unenhanced MRI, and contrast-enhanced MRI after gadoterate injection.

Drug: Gadoterate (Dotarem/Clariscan)

Arm 2_Confirmed CNS-lesion

EXPERIMENTAL

Patients with gadoterate-confirmed CNS-lesions (subgroup of Arm 1) underwent a second unenhanced MRI, and contrast-enhanced MRI after gadobutrol injection.

Drug: Gadoterate (Dotarem/Clariscan); Drug: Gadobutrol (Gadavist/Gadovist, BAY86-4875)

Interventions

Gadoterate (Dotarem/Clariscan) DRUG

Patients received a single dose of 0.5 molar gadoterate (0.1 mmol per kg body weight) intravenously.

Also known as: Gadoterate

Arm 1_Suspected CNS-lesion; Arm 2_Confirmed CNS-lesion

Gadobutrol (Gadavist/Gadovist, BAY86-4875) DRUG

Patients received a single dose of 1.0 molar BAY86-4875 (0.075 mmol per kg body weight) intravenously.

Also known as: Gadobutrol

Arm 2_Confirmed CNS-lesion

Eligibility Criteria

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

You may qualify if:

• Known or highly suspected central nervous system (CNS) pathology referred for contrast-enhanced MRI of the CNS.
• Glomerular filtration rate (eGFR) value ≥ 60 mL/min/1.73m2 derived from a serum creatinine result within four weeks prior to the first study MRI.
• Women with negative urine pregnancy test within 1 hour prior to the administration of gadoterate (the first MRI).

You may not qualify if:

• No enhancing lesion visible on the gadoterate-enhanced MRI scan.
• Pregnancy or breastfeeding.
• Severe cardiovascular disease

Sponsors & Collaborators

• Bayer: lead

Study Sites (20)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU STRASBOURG - Hôpital de Hautepierre

Strasbourg, 67098, France

Location

Universitätsklinikum Erlangen

Erlangen, Bavaria, 91054, Germany

Location

Universität Rostock - Medizinische Fakultät

Rostock, Mecklenburg-Vorpommern, 18057, Germany

Location

Universitätsklinikum Leipzig AöR

Leipzig, Saxony, 04103, Germany

Location

Universitätsklinikum Schleswig-Holstein (UKSH)

Kiel, Schleswig-Holstein, 24105, Germany

Location

Universitätsklinikum Schleswig-Holstein / AÖR

Lübeck, Schleswig-Holstein, 23538, Germany

Location

Friedrich-Schiller-Uni. Jena

Jena, Thuringia, 07740, Germany

Location

ASL Provincia di Barletta-Andria-Trani

Andria, Apulia, 70031, Italy

Location

A.O.U. Pisana

Pisa, Tuscany, 56126, Italy

Location

ULSS2 Marca Trevigiana

Treviso, Veneto, 31100, Italy

Location

Ulsan University Hospital

Ulsan, Ulsan Gwang''yeogsi, 44033, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Kantonsspital Aarau

Aarau, Canton of Aargau, 5001, Switzerland

Location

Inselspital Universitätsspital Bern

Bern, 3010, Switzerland

Location

Royal Preston Hospital

Preston, Lancashire, PR2 4HT, United Kingdom

Location

Related Publications (1)

• Liu BP, Rosenberg M, Saverio P, Weon YC, Peters S, Ardellier FD, Boeckenhoff A, Endrikat J. Clinical Efficacy of Reduced-Dose Gadobutrol Versus Standard-Dose Gadoterate for Contrast-Enhanced MRI of the CNS: An International Multicenter Prospective Crossover Trial (LEADER-75). AJR Am J Roentgenol. 2021 Nov;217(5):1195-1205. doi: 10.2214/AJR.21.25924. Epub 2021 Jun 16.

  PMID: 34133205 DERIVED

Related Links

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

MeSH Terms

Interventions

gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; gadoterate meglumine; ferumoxtran-10; gadobutrol

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer AG

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2018
• First Posted: July 26, 2018
• Study Start: November 14, 2018
• Primary Completion: March 13, 2020
• Study Completion: May 26, 2020
• Last Updated: June 14, 2021
• Results First Posted: April 28, 2021

Record last verified: 2021-05

Locations

FR (2); DE (6); IT (3); US (4); KR (2); CH (2); GB (1)