SAFETY AND EFFICACY EVALUATION OF DOTAREM® IN MAGNETIC RESONANCE IMAGING (MRI) IN PATIENTS WITH CENTRAL NERVOUS SYSTEM (CNS) LESIONS - SENTIO

• Register: EUCTR
• Last refreshed on: 11 September 2012
• Main ID: EUCTR2010-020319-34-DE
• Date of registration: 02/07/2010
• Prospective Registration: Yes
• Primary sponsor: GUERBET
• Public title: SAFETY AND EFFICACY EVALUATION OF DOTAREM® IN MAGNETIC RESONANCE IMAGING (MRI) IN PATIENTS WITH CENTRAL NERVOUS SYSTEM (CNS) LESIONS - SENTIO
• Scientific title: SAFETY AND EFFICACY EVALUATION OF DOTAREM® IN MAGNETIC RESONANCE IMAGING (MRI) IN PATIENTS WITH CENTRAL NERVOUS SYSTEM (CNS) LESIONS - SENTIO
• Date of first enrolment: 30/09/2010
• Target sample size: 396
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020319-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Austria, Germany, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
· Adult subject (having obtained legal majority age), and pediatric subjects (aged >= 2 years) who will be enrolled only in Latin America and/or in the USA.
· Having known or highly suspected of having at least one lesion with a disruption of BBB and/or with abnormal vascularity (including tumoral, vascular, inflammatory or infectious diseases) in the brain (intracranial) and spine, who are scheduled to undergo a routine contrast-enhanced MRI of the CNS. This/these lesion(s) must have been detected by previous imaging evaluation. Any of the following modalities are accepted: nuclear medicine imaging, contrast-enhanced CT, CT, contrast-enhanced MRI, MRI, or x-ray angiography. The prior imaging evaluation should be obtained within 6 months before study MRI.
· If patients treated (either with radiation, surgery, biopsy, steroid, or other relevant treatments) between previous imaging evaluation and study MRI, there is still a high suspicion of remaining lesion(s) with disrupted BBB and/or with abnormal vascularity on the basis of available clinical information.
· Female of childbearing potential patients must have effective contraception (contraceptive pill or intra-uterine device) or be surgically sterilized or post-menopausal (minimum 12 months amenorrhea), or have a documented negative urine pregnancy test within 24 hours prior to study MRI.
· Having provided their written informed consent to participate in the study. For patients under legal majority age, the parent(s) or legal guardian of the patient must give their written informed consent.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
· Having acute or chronic Grade IV or V renal insufficiency, defined as an estimated GFR<30 mL/min/1.73m² within 7 days before study MRI.
· Known Class III/IV congestive heart failure according to the New York Heart Association classification;
· Suffering from long QT syndrome.
· Unstable health condition or circumstances (e.g. suffering from severe claustrophobia).
· Having any contraindications to MRI such as a pacemaker, magnetic material or any other conditions that would preclude proximity to a strong magnetic field.
· Known allergy to Gadolinium chelates.
· Having received any contrast agent within 3 days prior to study contrast administration, or is scheduled to receive any contrast agent within 24 hours after the study contrast administration.
· Pregnant, breastfeeding, or planning to become pregnant during the study.
· Previously participated in this study.
· Having participated within 30 days in another clinical study involving an investigational drug.
· Any condition which, based on the investigator's clinical judgement, would prevent the patient from completing all study assessments and visits (for example: mental or physical incapacity, language comprehension, geographical localisation, etc…).
· Inability or unwillingness to cooperate with the requirements of this study.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patient with Central Nervous System (CNS) Lesions
MedDRA version: 12.1 Level: SOC Classification code 10029205 Term: Nervous system disorders

Intervention(s)

Trade Name: Dotarem 0,5 mmol/ml Injektionslösung in Durchstechflaschen
Product Name: Dotarem 0.5 mmol/ml, solution for injection in vials
Product Code: G449.06
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Gadoteric Acid
CAS Number: 60239-18-1
Other descriptive name: 1,4,7,10-tetraazacyclododecane-N, N',N",N'''-tetraacetic acid
Concentration unit: mmol/ml millimole(s)/millilitre
Concentration type: equal
Concentration number: 0.5-

Trade Name: Magnevist 0,5 mmol/ml Injektionslösung
Product Name: Magnevist
Pharmaceutical Form: Solution for injection
INN or Proposed INN: diethylenetriamine pentaacetic acid
CAS Number: 86050-77-3
Other descriptive name: GADOPENTETATE DIMEGLUMINE
Concentration unit: mmol/ml millimole(s)/millilitre
Concentration type: equal
Concentration number: 0.5-

Primary Outcome(s)

Secondary Objective: · Efficacy evaluation in terms of lesion visualization (on-site assessment).
· The location and number of lesions.
· Signal intensity (SI) measurement.
· The quality of images.
· The level of diagnostic confidence.
· The safety and efficacy of Dotarem® in pediatric population.
· The assessment by comparing Dotarem®-enhanced MRI to Magnevist®-enhanced MRI in terms of lesion visualization, the quality of images, the level of diagnostic confidence, the signal intensity, number and location of the lesions.
· Clinical safety and biological assessment by comparing Dotarem® to Magnevist® in terms of adverse events, injection-site tolerance, changes in vital signs and ECG recordings (for a subset of the study patients) and laboratory findings (time frame: up to 24 hours post-dose).
· Inter- and intra-reader agreement (off-site reading).

Main Objective: To demonstrate the superiority of Dotarem®-enhanced MRI as compared to unenhanced MRI in CNS (intracranial and spine) lesions in terms of lesion visualization (lesion border delineation, visualization of internal morphology and degree of contrast enhancement).

Blinded reading performed by three independent off-site readers (neuroradiologists) will be used to assess the study primary criteria. The study will be considered successful if two of the three readers simultaneously meet co-primary objectives.

Primary end point(s): Lesion visualization: border delineation, visualization of internal morphology and degree of contrast enhancement assessed by off-site reading.

Secondary ID(s)

DGD 44-050