Comparison of Gadovist 75% Standard Dose to Dotarem at Full Standard Dose (LEADER 75)

May 20, 2021 updated by: Bayer

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

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.

Study Overview

Detailed 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).

Study Type

Interventional

Enrollment (Actual)

157

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Pierre Benite, France, 69495
        • Centre Hospitalier Lyon Sud
      • Strasbourg, France, 67098
        • CHU STRASBOURG - Hôpital de Hautepierre
    • Bayern
      • Erlangen, Bayern, Germany, 91054
        • Universitätsklinikum Erlangen
    • Mecklenburg-Vorpommern
      • Rostock, Mecklenburg-Vorpommern, Germany, 18057
        • Universität Rostock - Medizinische Fakultät
    • Sachsen
      • Leipzig, Sachsen, Germany, 04103
        • Universitätsklinikum Leipzig AÖR
    • Schleswig-Holstein
      • Kiel, Schleswig-Holstein, Germany, 24105
        • Universitatsklinikum Schleswig-Holstein (UKSH)
      • Lübeck, Schleswig-Holstein, Germany, 23538
        • Universitätsklinikum Schleswig-Holstein / AÖR
    • Thüringen
      • Jena, Thüringen, Germany, 07740
        • Friedrich-Schiller-Uni. Jena
    • Puglia
      • Andria, Puglia, Italy, 70031
        • ASL Provincia di Barletta-Andria-Trani
    • Toscana
      • Pisa, Toscana, Italy, 56126
        • A.O.U. Pisana
    • Veneto
      • Treviso, Veneto, Italy, 31100
        • ULSS2 Marca Trevigiana
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital
    • Ulsan Gwang''yeogsi
      • Ulsan, Ulsan Gwang''yeogsi, Korea, Republic of, 44033
        • Ulsan University Hospital
      • Bern, Switzerland, 3010
        • Inselspital Universitätsspital Bern
    • Aargau
      • Aarau, Aargau, Switzerland, 5001
        • Kantonsspital Aarau
    • Lancashire
      • Preston, Lancashire, United Kingdom, PR2 4HT
        • Royal Preston Hospital
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
    • New York
      • New York, New York, United States, 10029
        • Mount Sinai Hospital
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Penn State Milton S. Hershey Medical Center
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1_Suspected CNS-lesion
Patients with suspected or confirmed CNS-lesions underwent unenhanced MRI, and contrast-enhanced MRI after gadoterate injection.
Patients received a single dose of 0.5 molar gadoterate (0.1 mmol per kg body weight) intravenously.
Other Names:
  • Gadoterate
Experimental: Arm 2_Confirmed CNS-lesion
Patients with gadoterate-confirmed CNS-lesions (subgroup of Arm 1) underwent a second unenhanced MRI, and contrast-enhanced MRI after gadobutrol injection.
Patients received a single dose of 0.5 molar gadoterate (0.1 mmol per kg body weight) intravenously.
Other Names:
  • Gadoterate
Patients received a single dose of 1.0 molar BAY86-4875 (0.075 mmol per kg body weight) intravenously.
Other Names:
  • Gadobutrol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Degree of Lesion Contrast Enhancement
Time Frame: Up to 20 days
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
Time Frame: Up to 20 days
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
Time Frame: Up to 20 days
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Lesions Identified
Time Frame: Up to 20 days
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
Detection of Malignant Disease
Time Frame: Up to 20 days

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
Confidence in Diagnosis
Time Frame: Up to 20 days
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
Image Quality
Time Frame: Up to 20 days
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
Contrast Enhancement Utilizing an Exploratory Overall Contrast Enhancement Estimation Algorithm
Time Frame: Up to 20 days
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
Number of Participants With Treatment-emergent Adverse Events
Time Frame: From the first study drug administration up to 24 hours post injection
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 14, 2018

Primary Completion (Actual)

March 13, 2020

Study Completion (Actual)

May 26, 2020

Study Registration Dates

First Submitted

July 17, 2018

First Submitted That Met QC Criteria

July 18, 2018

First Posted (Actual)

July 26, 2018

Study Record Updates

Last Update Posted (Actual)

June 14, 2021

Last Update Submitted That Met QC Criteria

May 20, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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