To determine the accuracy of Vasovist® enhanced MRA of the leg with regard to quantitative grading of stenosis (=50%) compared to digital subtraction angiography (DSA, standard of reference (SOR))
ID
Source
Brief title
Condition
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
This study will be conducted to determine the diagnostic accuracy of Vasovist*
enhanced MRA in stenosis grading (<50%, >=50%) with regard to DSA as SOR for
the defined segments. To have a sufficient prevalence of stenotic lesions all
patients in this study have to be scheduled for therapeutic DSA of one leg.
Secondary outcome
The secondary efficacy variables are
• to determine the proportion of correct stenosis gradings (<50%, 50-99%,
occlusion) of Vasovist® enhanced MRA compared to DSA
• to calculate the sensitivity and specificity (<50%, >=50%) of Vasovist
enhanced MRA compared to DSA
• to correlate the determination of the length of stenosis (target) of
Vasovist® enhanced MRA compared to DSA
• to correlate the description of the inflow, target, outflow of Vasovist®
enhanced MRA (combined) compared to DSA [what is target lesion? , is it
significant [>50%]?, is there disease in inflow segment?, determination of
outflow y/n, significant disease in outflow]? Determined in a consensus reading)
• to determine the number of patients with change of therapeutic approach after
reviewing Vasovist enhanced MRA compared to initial non-invasive angiography
(MRA, CTA, US)
• to evaluate the diagnostic value (detection of target lesion y/n) of
time-resolved first pass MRA in comparison to high-spatial resolution steady
state MRA
• Additional venous pathologies: thrombus (y/n), venous aneurysm, varicosis
(y/n), clinical relevance?
• to evaluate the diagnostic confidence of Vasovist enhanced MRA and DSA
Safety variables in this study will include the evaluation of physical
examinations and vital signs as well as the assessment of adverse events (AEs)
for Vasovist* enhanced MRA.
Background summary
Digital subtraction angiography (DSA) of the lower extremity is still the
diagnostic modality of choice for the detection and grading of vascular lesions
in patients with peripheral arterial occlusive disease (PAOD). It is
characterized by a high inplane resolution of 0.3 mm² and also allows for
dynamic imaging to show hemodynamic alterations. It is however also
characterized by an approximately 1%-2% risk for severe side effects including
stroke and even death. In addition, the administration of iodinated contrast
agents in patients suffering from PAOD who are often concomitantly suffering
from chronic renal failure carries the risk of contrast-induced nephropathy
which leads to a substantially increased mortality in affected patients. The
therapeutic DSA cannot be replaced by other modalities at this time.
In contrast, the technical advances and new MR-contrast agents have made
high-spatial resolution magnetic resonance angiography (MRA) a challenger for
diagnostic imaging. Conventional, extracellular contrast agents (ECCM),
optimized MR-scanner and parallel imaging allow for submillimeter
three-dimensional MRA of the lower extremity during the first pass of the
contrast agent. Due to the singularity of the first pass of ECCM and the fast
extravasation of ECCM into the interstitium either no ultra-high spatial
resolution MRAs can be acquired as the required measurement times exceed
available imaging times. It is also not feasible to obtain dynamic images and
high-spatial resolution images after a single injection of ECCM.
Intravascular contrast agents like gadofosveset (Vasovist®) can overcome this
limitation because they allow for minute-long image acquisition. The newly
developed blood pool contrast agent Vasovist* provides a prolonged imaging
window of about 1 hour. Vasovist* is the designation for the drug product which
has the active pharmaceutical ingredient: gadofosveset
trisodium{(2(R)[(4,4iphenylcyclohexyl)-phosphonooxymethyl]-diethyl-enetriamine-p
entaacetato)(aquo)gadolinium(III)}, formulated as 244 mg/mL. Due to reversible
binding to albumin the relaxivity of Vasovist* is increased which allows lower
doses for the same contrast effect and additionally prolongs vascular
persistence. Compared to conventional ECCM, T1 relaxivity is about 4-5 times
higher at 1.5T which is the field strength of most clinically used scanners.
With Vasovist® three-dimensional image data with less than 0.5x0.5x0.5 mm³ can
be acquired. Hence, MRA with intravascular contrast agents almost reaches the
inplane resolution of MRA but has the added advantage of being
three-dimensional. In addition, the first pass of the contrast agent can be
used to acquire time-resolved MRA data. The combination of dynamic imaging
during the first pass and ultra-high spatial resolution imaging during the
steady state precludes typical MRA errors such as missing the contrast agent
bolus and reduces the risk of non-diagnostic images due to patient motion.
The aim of this study is to evaluate the diagnostic accuracy of
gadofosveset-enhanced MRA in detecting and grading vascular lesions in patients
suffering from PAOD stage III° or IV° using intra-arterial digital subtraction
angiography (i.a. DSA) as standard of reference (SOR).
The study will be conducted in compliance with the protocol, ICH-GCP and any
applicable regulatory requirements.
Study objective
To determine the accuracy of Vasovist® enhanced MRA of the leg with regard to
quantitative grading of stenosis (<50%, >=50%) compared to digital subtraction
angiography (DSA, standard of reference (SOR))
Study design
Multicenter, multinational, intra-individual, open label study with an
independent blinded off-site evaluation for MRA by two radiologists and for
i.a. DSA by one radiologist. In case the assessments of the two MRA readers are
contradictory a third independent reader will be involved for clarification
Study burden and risks
MRA is a very safe examination method. So far, neither risk to health nor side
effects have been observed in the used magnetic field strengths. The
examination is completely painless, however, it is accompanied by a loud
knocking sound. For this reason ear protectors will be at the patients*
disposal. Due to the strong magnetic fields required for this examination,
which amount to a thousandfold of the earth*s magnetic field, patients with
metal implants (e.g. shell splinters) may only be examined within certain
limits. Dependent on their metallic characteristics and dimension, metals in
the body can cause problems. Aside from being moved by the magnetic field,
metal objects can get too warm during the examination. Fixed dental implants,
however, usually do not lead to problems in MRA examinations. In case of other
metal implants (artificial joints, metal splinters to support broken bones,
etc.), it has to be decided individually whether or not they may cause problems
during MRA. In the course of the studies carried out so far the most frequent
complaints (i.e. occurrence in 1% or more of the patients receiving Vasovist*)
were: Pruritus, Paresthesia, Headaches, Nausea, Vasodilatation, Burning
Sensation and Dysgeusia. These complaints were usually only of short duration.
Theodor-Kutzer-Ufer 1-3
68167 Mannheim
Duitsland
Theodor-Kutzer-Ufer 1-3
68167 Mannheim
Duitsland
Listed location countries
Age
Inclusion criteria
1. Patients who have Fontaine-stage III and IV and an indication for therapeutic i.a. DSA
2. PAOD has to be confirmed by ECCM MRA, CTA, non-selective DSA, Doppler ultrasound (DUS) prior to the study.
3. Patients who are willing to undergo the study MRA procedure with Vasovist*.
4. Patients who are willing to comply with the study procedures (e.g. being followed-up for 12 hours after the Vasovist* injection).
5. Patients who have given their fully informed and written consent voluntarily.
Exclusion criteria
1. Being less than 18 years of age.
2. Women who are pregnant, lactating or who are of childbearing potential and have not had a negative urine pregnancy test the same day as administration of Vasovist*. The manufacturer*s instructions for performing the urinary pregnancy test are to be followed.
3. Patients who are scheduled for any therapy between any of the two procedures (MRA and DSA) that interferes with the comparability of the two angiographic procedures.
4. Having an underlying disease or concomitant medication which may interfere with efficacy or safety evaluations as planned in this study.
5. Having any physical or mental status that interferes with the informed consent procedure including self-signed consent.
6. GFR < 30ml/m²/1.73m² (MDRD), values <= 1 week or patients on hemodialysis
7. Renal or liver transplant patients, including patients with scheduled liver transplant are excluded due to the potential risk for nephrogenic systemic fibrosis (NSF).
8. MR contraindications (pacemaker, magnetic clips, severe claustrophobia)
9. Known allergy to Gadofosveset
10. Presenting with history of anaphylactoid or anaphylactic reaction to any allergen including drugs and contrast agents.
11. Untreated significant stenosis in pelvis
12. Known severe coagulopathy (PTT >25s, Quick < 60%)
13. Having received any investigational drug within 7 days prior to entering this study or who are planned to receive any investigational drug during the safety follow-up period.
14. Not being able to remain lying down for at least 30-45min (e.g. patients with unstable angina, dyspnea at rest, severe pain at rest, severe back pain).
15. Being clinically unstable and whose clinical course during the 12 hours observation period is unpredictable.
16. Being scheduled for, or likely to require, any surgical intervention within 12 hours before or within the follow-up period.
17. Patients in whom i.a. DSA is contra-indicated preventing him/her from undergoing standard of reference (SOR) procedure.
18. Close affiliation with the investigational site; e.g. a close relative of the investigator.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-006014-41-NL |
| ClinicalTrials.gov | NCT00717639 |
| CCMO | NL22483.068.08 |