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

Magnetic Resonance Imaging Clinical Trial

— LEADER 75  

Official title:

LowEr Administered Dose With highEr Relaxivity: Gadovist vs Dotarem (LEADER 75)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03602339
• Other study ID #: 19773
• Secondary ID: 2018-000690-78
• Status: Completed
• Phase: Phase 4
• Start date: November 14, 2018
• Est. completion date: May 26, 2020

Study information

• Verified date: May 2021
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The study was an open-label, multi-center, comparative, cross-over trial in adult patients with known or highly suspected CNS pathology who were referred for imaging of the CNS. The primary objective of the study was to demonstrate the non-inferiority of gadobutrol (0.075 mmol/ kg body weight) to gadoterate (0.1 mmol/ kg body weight).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 157
• Est. completion date: May 26, 2020
• Est. primary completion date: March 13, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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).

Exclusion Criteria:

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

Related Conditions & MeSH terms

• Magnetic Resonance Imaging

Intervention

Drug:
• Gadoterate (Dotarem/Clariscan)
Patients received a single dose of 0.5 molar gadoterate (0.1 mmol per kg body weight) intravenously.
• Gadobutrol (Gadavist/Gadovist, BAY86-4875)
Patients received a single dose of 1.0 molar BAY86-4875 (0.075 mmol per kg body weight) intravenously.

Locations

Country	Name	City	State
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	CHU STRASBOURG - Hôpital de Hautepierre	Strasbourg
Germany	Universitätsklinikum Erlangen	Erlangen	Bayern
Germany	Friedrich-Schiller-Uni. Jena	Jena	Thüringen
Germany	Universitätsklinikum Schleswig-Holstein (UKSH)	Kiel	Schleswig-Holstein
Germany	Universitätsklinikum Leipzig AöR	Leipzig	Sachsen
Germany	Universitätsklinikum Schleswig-Holstein / AÖR	Lübeck	Schleswig-Holstein
Germany	Universität Rostock - Medizinische Fakultät	Rostock	Mecklenburg-Vorpommern
Italy	ASL Provincia di Barletta-Andria-Trani	Andria	Puglia
Italy	A.O.U. Pisana	Pisa	Toscana
Italy	ULSS2 Marca Trevigiana	Treviso	Veneto
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Ulsan University Hospital	Ulsan	Ulsan Gwang''yeogsi
Switzerland	Kantonsspital Aarau	Aarau	Aargau
Switzerland	Inselspital Universitätsspital Bern	Bern
United Kingdom	Royal Preston Hospital	Preston	Lancashire
United States	Northwestern University	Chicago	Illinois
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Mount Sinai Hospital	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Korea, Republic of,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Number of Lesions Identified	Number of lesions identified (up to 10) detected by 3 blinded Readers. The mean (SD) number lesions in the Average Reader for gadobutrol and gadoterate in the Full Analysis Set was reported below.	Up to 20 days
Secondary	Detection of Malignant Disease	The 3 Blinded Readers had to evaluate if the diagnosis resulting from the combined images was malignant disease or not. Each blinded Reader provided a malignant yes/no response. This was compared to the final diagnosis provided by the Investigator. The majority of Readers (2 or 3 Readers agree) was used to calculate sensitivity, specificity, and accuracy - eg. Final Diagnosis - Malignant (Reader 1-yes, Reader 2-no, Reader 3-yes --- Majority Reader yes) - this would be a match for sensitivity.; The percentage of sensitivity, specificity, and accuracy of detection of malignant disease detected by 3 blinded Readers, gadobutrol versus gadoterate (Full Analysis Set) is reported below for Majority Readers.	Up to 20 days
Secondary	Confidence in Diagnosis	Diagnostic confidence detected by 3 blinded Readers, gadobutrol vs gadoterate (Full Analysis Set). Blinded Readers rated their confidence in diagnosis according to a 4-point scale (1 - Not confident; 2 - Somewhat confident; 3 - Confident; 4 - Very confident). Results for the Average Reader are reported below.	Up to 20 days
Secondary	Image Quality	Comparison of image quality between gadobutrol and gadoterate detected by 3 blinded Readers (Full Analysis Set). Blinded Readers assessed the image quality of gadobutrol- and gadoterate-enhanced images (randomly assigned as left [L] and right [R] image positions) according to a 5-point scale (1- Image R is worse; 2 - Image R is slightly worse; 3- Image R is similar; 4 - Image R is slightly better; 5 - Image R is better). After unblinding of data, the above codes were translated into the following scale: -2 = Gadobutrol image set is worse ; -1 = Gadobutrol image set is slightly worse ; 0 = Image sets are the same ; 1 = Gadobutrol image set is slightly better; 2 = Gadobutrol image set is better. Results for the Average Reader are reported below.	Up to 20 days
Secondary	Contrast Enhancement Utilizing an Exploratory Overall Contrast Enhancement Estimation Algorithm	Comparison of contrast enhancement utilizing an overall contrast enhancement estimation algorithm (Full Analysis Set). The exploratory algorithm analyzed the overall enhancement by comparing the axial T1w (longitudinal relaxation time-weighted) enhanced images to the T1w unenhanced images.	Up to 20 days
Secondary	Number of Participants With Treatment-emergent Adverse Events	Number of subjects with treatment-emergent adverse events (TEAEs) (Safety Analysis Set). TEAEs are defined as any AEs that increase in intensity or that are newly developed during the TE period for Study Period 1 or Study Period 2, where TE period for Study Period 1 goes from the first study drug administration in Study Period 1 to 24 hours post-injection, and TE period for Study Period 2 from the first study drug administration in Study Period 2 to 24 hours post-injection.	From the first study drug administration up to 24 hours post injection

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