Efficacy evaluation of MRA images injected with a contrast product for patient suffering from abdominal or lower limb arterial diseases: Comparison of 2 products DOTAREM® and GADOVIST®.

• Register: EUCTR
• Last refreshed on: 24 April 2012
• Main ID: EUCTR2009-010968-42-DE
• Date of registration: 03/07/2009
• Prospective Registration: Yes
• Primary sponsor: GUERBET
• Public title: Efficacy evaluation of MRA images injected with a contrast product for patient suffering from abdominal or lower limb arterial diseases: Comparison of 2 products DOTAREM® and GADOVIST®.
• Scientific title: Efficacy evaluation of DOTAREM®-enhanced MRA compared to GADOVIST®–enhanced MRA in the diagnosis of clinically significant abdominal or lower limb arterial diseases - DALIA
• Date of first enrolment: 22/12/2009
• Target sample size: 188
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-010968-42
• 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 Number of treatment arms in the trial: 2

Countries of recruitment

Austria, France, Germany, Italy, Spain

Contacts

• Name: Head of Medical and Regulatory Affa
• Affiliation: Guerbet

• Name: Head of Medical and Regulatory Affa
• Affiliation: Guerbet

Key inclusion & exclusion criteria

Inclusion criteria:
- Male or female, aged = 18 years
- Patient with infrarenal aorta or chronic lower limb ischemia with various clinical signs of gravity (stages II-IV according to the classification of Leriche and Fontaine) or/and Doppler ultrasonography indicating abdominal or lower limb arteriopathy.
- Patient scheduled for a conventional X-Ray angiography (intra-arterial Digital Substraction Angiography = DSA) within 30 days of MRA with a minimum time interval of at least 24 hours between the 2 examinations.
- Female of childbearing potential must have effective contraception (contraceptive pill or Intra-Uterine Device), or be surgically sterilized, or post-menopausal (minimum 12 months of amenorrhea) or must have a documented negative urine or blood pregnancy test at screening
- Patient able to understand and who have provided written informed consent to participate in the trial.
- Patient with national health insurance

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 188
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 188

Exclusion criteria:
- Patient with a contraindication to MRI (e.g., pacemaker, aneurysm clip, severe claustrophobia, metallic joint replacement or others according to the imaging laboratory's standard practice).
- Patient with known severe adverse drug reaction or contraindication to one of the investigational products (Dotarem® or Gadovist®).
- Patient having received any contrast media within 48 hours prior to administration of investigational product for the enhanced-MRA.
- Patient planned to undergo therapeutic intervention in abdominal or lower limb vessels between the time of MRA and X-ray Angiography will be performed.
- Patient who had a major cardiovascular event within 30 days prior to the inclusion.
- Patient treated with extra-anatomic bypass from axillar artery to the iliacs, iliaco-femoral bypass grafts, ipsilateral stents and ipsilateral knee and/or hip prosthesis.
- Patient having participated in any investigational drug study within 30 days prior the study enrolment.
- Any condition which, based on the investigator's clinical judgement, would prevent the patient from completing all trial assessments and visits (for example: mental or physical incapacity, language comprehension, geographical localisation, etc…).
- Patient under guardianship and/or Inability or unwillingness to cooperate with the requirements of this trial.
- Pregnant or breast-feeding patient.
- Patients already included in this trial



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

Health Condition(s) or Problem(s) studied

Patient suffering from abdominal or lower limb arterial diseases
MedDRA version: 13.1 Level: PT Classification code 10062585 Term: Peripheral arterial occlusive disease System Organ Class: 10047065 - Vascular disorders

Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

Intervention(s)

Trade Name: Dotarem 0.5mmol/ml
Product Name: Dotarem 0.5mmol/ml, solution for injection in vials
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Gadoteric Acid (corresponding to Dota+gadolinium oxide)
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: Gadovist 1mmol/ml
Product Name: Gadovist 1mmol/ml, solution for injection
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Gadobutrol
CAS Number: 138071-82-6
Concentration unit: mmol/ml millimole(s)/millilitre
Concentration type: equal
Concentration number: 1-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: first and second visit for the patient (enhanced-MRA , and DSA)

Main Objective: To demonstrate the clinical equivalence (statistical non-inferiority) in terms of global diagnostic performance of DOTAREM®-enhanced MRA as compared to GADOVIST® - enhanced MRA by comparing the degree of agreement at the patient level of each MRA method when using X-Ray Angiography (DSA) as a gold standard.

Primary end point(s): The primary criterion is the intra patient accuracy (percent agreement) of each type of MRA examination (DOTAREM® or GADOVIST®-enhanced MRA) in assessing the lesions of the concerned territory as compared with the gold standard, X-ray angiography. This criterion will be evaluated at the patient level from the result of site reading. On site readers will be differents and blind from results of the other imaging procedures (MRA and DSA).

Secondary Objective: Demonstrate, in off-site reading conditions, the clinical equivalence in terms of global diagnostic performance of DOTAREM®-enhanced MRA as compared to GADOVIST® - enhanced MRA by comparing the degree of agreement at the patient level of each MRA method when using X-Ray
Angiography as a gold standard.
Compare diagnostic criteria of DOTAREM®-enhanced MRA and GADOVIST®-enhanced MRA using X-Ray Angiography as a gold standard in on-site and off-site reading conditions.
Compare, in on-site and off-site reading conditions, DOTAREM®-
enhanced MRA versus GADOVIST®-enhanced MRA in terms of :
o artery visualization,
o significant stenosis depicted,
o non assessable segment,
o duration of examination,
o collateral circulation visualization,
o pedal vessel and smaller branches visualization,
o diagnostic confidence
o patient clinical management
o venous overlap
Compare clinical tolerance (AE) of both contrast media from inclusion and up to the last visit performed.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: first and second visit for the patient (enhanced-MRA , and DSA) for
efficacy endpoints.
patient's study participation for safety endpoint

Secondary end point(s): 1. Only on data from the examination corresponding to the vascular territory for which the subject entered the trial:
- Intra patient accuracy (percent agreement) of each type of MRA examination (DOTAREM® or GADOVIST®-enhanced MRA) in assessing the lesions of the concerned territory as compared with the gold standard, X-ray angiography, in off-site reading conditions. Same methodology will be used as for the primary criterion.
- Specificity and sensitivity of DOTAREM® and GADOVIST®-enhanced MRA examinations at the segment and the patient levels (gold standard = x-ray angiography) in on-site and off-site reading conditions; in this analysis moderate, severe stenosis and occlusion will be collapsed in one class (=significant stenosis).
- Positive and negative predictive values of DOTAREM® and GADOVIST®-enhanced MRA examinations at the segment and the patient levels (gold standard = x-ray angiography) in on-site and off-site reading conditions; in this analysis moderate, severe stenosis and occlusion will be collapsed in one class (=significant stenosis).

2. On all the available data from MRA examination:
- Number of evaluated arterial segments and number of segments with >50% stenosis in on-site and off-site reading conditions.
- Proportion of non-assessable segments (or technical failure rate) in on-site and off-site reading conditions: A segment will be considered by the reader as "not assessable" if:
-- its image does not allow the reader to determine whether this segment is affected by a stenosis,
or
-- in case of stenosis, its image does not allow the reader to measure the detected stenosis (grade of stenosis).
- The artery visualization assessed by patient on a 4-point scale in onsite and off-site reading conditions:
(1) Providing the expected information (totally satisfactory);
(2) Providing sufficient information (satisfactory);
(3) Not providing all the expected information (not satisfactory, could need a complementary examination);
(4) Not providing enough information (not satisfactory, complementary examination recommended).
When the evaluation is (3) or (4), the reason for such evaluation (technical problem, restless patient, insufficient contrast, artifacts or other) will be described in the CRF.
- The collateral circulation visualization in on-site and off-site reading conditions assessed by using a 4-point scale by patient:
(1) Providing the expected information (totally satisfactory);
(2) Providing sufficient information (satisfactory);
(3) Not providing all the expected information (not satisfactory, could need a complementary examination);
(4) Not providing enough information (not satisfactory, complementary examination recommended).
When the evaluation is (3) or (4), the reason for such evaluation (technical problem, restless patient, insufficient contrast, artifacts or other) will be described in the CRF.
- The pedal vessel and smaller branches graded for visualization on a 4-
point scale in the foot territory by patient, in on-site and off-site reading conditions:
(1) Excellent visualization
(2) Adequate visualization
(3) Poor visualization
(4) Non visualized
- The venous overlap that interfered with arterial visualization evaluated on a 4-grade scale by patient, in on-site reading conditions:
(5) not seen: no venous overlap depicted
(6) partially seen: venous overlap partially depicted but not difficult to distinguish from the artery
(7) seen: venous overlap difficult to distinguish from the artery
(8) unassessable
- Level of diagnostic confidence assessed on a 5-point scale by patient in on-site and off-site reading conditions: nil, poor, moderate, high,
excellent
- Patient's clinical management in on-site reading conditions: no action needed, need for surgery, angioplasty, extent of surgery, extent of angioplasty, medical supervision with/without medication treatment, additional examination required, other.
3. Duration of examination defined as the time between the start of the bolus injection and the end of the image acquisition for MRA and x-ray angiography;
4. The following safety criteria will by assessed:
Adverse events will be assessed during the patient's study participation.
Additionally, following the contrast product bolus injection for MRA examination, patients are to be followed over a 1/2 hour period for clinical safety (vital signs and injection-site tolerance) and until the last visit performed for AE .

Secondary ID(s)

DGD-44-045

2009-010968-42-FR

Source(s) of Monetary Support

Guerbet