Magnetic Resonance ImagingPhase 4LEADER 75NCT03602339
Comparison of Gadovist 75% Standard Dose to Dotarem at Full Standard Dose
A Phase 4 study testing Gadoterate (Dotarem/Clariscan) and Gadobutrol (Gadavist/Gadovist, BAY86-4875) in people with Magnetic Resonance Imaging, run by Bayer at 20 sites in 7 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Magnetic Resonance Imaging
- What is being tested?
- Gadoterate (Dotarem/Clariscan) and Gadobutrol (Gadavist/Gadovist, BAY86-4875)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 157 participants
- Where
- 20 sitesin 7 countries
- Study dates
- 14 Nov 2018to 26 May 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- No enhancing lesion visible on the gadoterate-enhanced MRI scan.
- Pregnancy or breastfeeding.
- Severe cardiovascular disease
Trial locations and contacts
20 sites in 7 countries.
20 sites in 7 countries
Germany6 sites
Universitätsklinikum Erlangen
Erlangen, Bavaria, 91054
Friedrich-Schiller-Uni. Jena
Jena, Thuringia, 07740
Universitätsklinikum Schleswig-Holstein (UKSH)
Kiel, Schleswig-Holstein, 24105
Universitätsklinikum Leipzig AöR
Leipzig, Saxony, 04103
Universitätsklinikum Schleswig-Holstein / AÖR
Lübeck, Schleswig-Holstein, 23538
Universität Rostock - Medizinische Fakultät
Rostock, Mecklenburg-Vorpommern, 18057
United States4 sites
Northwestern University
Chicago, Illinois, 60611
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
Mount Sinai Hospital
New York, New York, 10029
Italy3 sites
ASL Provincia di Barletta-Andria-Trani
Andria, Apulia, 70031
A.O.U. Pisana
Pisa, Tuscany, 56126
ULSS2 Marca Trevigiana
Treviso, Veneto, 31100
France2 sites
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495
CHU STRASBOURG - Hôpital de Hautepierre
Strasbourg, 67098
South Korea2 sites
Seoul National University Hospital
Seoul, 03080
Ulsan University Hospital
Ulsan, Ulsan Gwang''yeogsi, 44033
Switzerland2 sites
Kantonsspital Aarau
Aarau, Canton of Aargau, 5001
Inselspital Universitätsspital Bern
Bern, 3010
United Kingdom1 site
Royal Preston Hospital
Preston, Lancashire, PR2 4HT
About this study
Official title: 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.
Read the 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).
- Conditions
- Magnetic Resonance Imaging
- Being tested
- Gadoterate (Dotarem/Clariscan), Gadobutrol (Gadavist/Gadovist, BAY86-4875)
- Keywords
- Gadolinium, Contrast enhancement, Central nervous system lesion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gadoterate (Dotarem/Clariscan)Drug
Also called Gadoterate
Patients received a single dose of 0.5 molar gadoterate (0.1 mmol per kg body weight) intravenously.
Gadobutrol (Gadavist/Gadovist, BAY86-4875)Drug
Also called Gadobutrol
Patients received a single dose of 1.0 molar BAY86-4875 (0.075 mmol per kg body weight) intravenously.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1_Suspected CNS-lesion | Experimental | Patients with suspected or confirmed CNS-lesions underwent unenhanced MRI, and contrast-enhanced MRI after gadoterate injection. Receives: 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. Receives: Drug: Gadoterate (Dotarem/Clariscan); Drug: Gadobutrol (Gadavist/Gadovist, BAY86-4875) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 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)
Measured: Up to 20 days
Secondary outcomes (6)
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.
Measured: Up to 20 days
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.
Measured: Up to 20 days
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.
Measured: Up to 20 days
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.
Measured: Up to 20 days
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.
Measured: Up to 20 days
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.
Measured: From the first study drug administration up to 24 hours post injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2018
- Study start14 Nov 2018
- Primary completion13 Mar 2020
- Study completion26 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Magnetic Resonance ImagingStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 157 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03602339
- Sponsor's protocol ID
- 19773
- Other IDs
- 2018-000690-78, 2018
- Acronym
- LEADER 75
- Status last verified
- May 2021
- First submitted
- 17 Jul 2018
- Last updated
- 14 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 34133205
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LowEr Administered Dose With highEr Relaxivity: Gadovist vs Dotarem (LEADER 75)
- ClinicalTrials.gov ID
- NCT03602339
- Acronym / sponsor ID
- LEADER 75 / 19773
- Conditions
- Magnetic Resonance Imaging
- Keywords
- Gadolinium, Contrast enhancement, Central nervous system lesion
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 157 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 14 Nov 2018 (actual)
- Primary completion
- 13 Mar 2020 (actual)
- Study completion
- 26 May 2020 (actual)
- First posted
- 26 Jul 2018 (actual)
- Results
- Posted 28 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1_Suspected CNS-lesion | Experimental | Drug: Gadoterate (Dotarem/Clariscan)Patients with suspected or confirmed CNS-lesions underwent unenhanced MRI, and contrast-enhanced MRI after gadoterate injection. |
| Arm 2_Confirmed CNS-lesion | Experimental | Drug: Gadoterate (Dotarem/Clariscan), Drug: Gadobutrol (Gadavist/Gadovist, BAY86-4875)Patients with gadoterate-confirmed CNS-lesions (subgroup of Arm 1) underwent a second unenhanced MRI, and contrast-enhanced MRI after gadobutrol injection. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (3 listed)
- No enhancing lesion visible on the gadoterate-enhanced MRI scan.
- Pregnancy or breastfeeding.
- Severe cardiovascular disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gadoterate (Dotarem/Clariscan)Also: GadoteratePatients received a single dose of 0.5 molar gadoterate (0.1 mmol per kg body weight) intravenously. | Drug | Arm 1_Suspected CNS-lesion, Arm 2_Confirmed CNS-lesion |
| Gadobutrol (Gadavist/Gadovist, BAY86-4875)Also: GadobutrolPatients received a single dose of 1.0 molar BAY86-4875 (0.075 mmol per kg body weight) intravenously. | Drug | Arm 2_Confirmed CNS-lesion |
Primary outcome
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).
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).
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)
6 secondary outcomes
Number of Lesions Identified
Time frame: Up to 20 days
Detection of Malignant Disease
Time frame: Up to 20 days
Confidence in Diagnosis
Time frame: Up to 20 days
Image Quality
Time frame: Up to 20 days
Contrast Enhancement Utilizing an Exploratory Overall Contrast Enhancement Estimation Algorithm
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34133205Liu 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.
- Click here to find information about studies related to Bayer Healthcare products conducted in Europe.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
20 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Gadoterate (Dotarem/Clariscan) and Gadobutrol (Gadavist/Gadovist, BAY86-4875) in people with Magnetic Resonance Imaging, run by Bayer at 20 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Germany, United States, Italy, France, South Korea and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Degree of Lesion Contrast Enhancement (time frame: Up to 20 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03602339, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2021.