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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03602339
Recruitment Status : Completed
First Posted : July 26, 2018
Results First Posted : April 28, 2021
Last Update Posted : June 14, 2021
Sponsor:
Information provided by (Responsible Party):
Bayer

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.


Condition or disease Intervention/treatment Phase
Magnetic Resonance Imaging Drug: Gadoterate (Dotarem/Clariscan) Drug: Gadobutrol (Gadavist/Gadovist, BAY86-4875) Phase 4

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 157 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: LowEr Administered Dose With highEr Relaxivity: Gadovist vs Dotarem (LEADER 75)
Actual Study Start Date : November 14, 2018
Actual Primary Completion Date : March 13, 2020
Actual Study Completion Date : May 26, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: MRI Scans

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.
Drug: Gadoterate (Dotarem/Clariscan)
Patients received a single dose of 0.5 molar gadoterate (0.1 mmol per kg body weight) intravenously.
Other Name: 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.
Drug: Gadoterate (Dotarem/Clariscan)
Patients received a single dose of 0.5 molar gadoterate (0.1 mmol per kg body weight) intravenously.
Other Name: Gadoterate

Drug: Gadobutrol (Gadavist/Gadovist, BAY86-4875)
Patients received a single dose of 1.0 molar BAY86-4875 (0.075 mmol per kg body weight) intravenously.
Other Name: Gadobutrol




Primary Outcome Measures :
  1. 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).

  2. 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).

  3. 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)


Secondary Outcome Measures :
  1. 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.

  2. 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.


  3. 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.

  4. 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.

  5. 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.

  6. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03602339


Locations
Show Show 20 study locations
Sponsors and Collaborators
Bayer
  Study Documents (Full-Text)

Documents provided by Bayer:
Study Protocol  [PDF] March 26, 2019
Statistical Analysis Plan  [PDF] March 18, 2021

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT03602339    
Other Study ID Numbers: 19773
2018-000690-78 ( EudraCT Number )
First Posted: July 26, 2018    Key Record Dates
Results First Posted: April 28, 2021
Last Update Posted: June 14, 2021
Last Verified: May 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bayer:
Gadolinium
Contrast enhancement
Central nervous system lesion
Additional relevant MeSH terms:
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Gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action