E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patient suffering from abdominal or lower limb arterial diseases |
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E.1.1.1 | Medical condition in easily understood language |
Patient suffering from abdominal or lower limb arterial diseases |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062585 |
E.1.2 | Term | Peripheral arterial occlusive disease |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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
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E.5 End points |
E.5.1 | 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). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
first and second visit for the patient (enhanced-MRA , and DSA) |
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E.5.2 | 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 . |
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E.5.2.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The day of the last off-site image reading |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |