Critical Limb Ischemia: MRA And CTA Study (Feasibility)

Critical limb ischemia (CLI) is a severe symptom of peripheral arterial disease
(PAD) and is characterized by ischemic pain at rest or non-healing ischemic
ulcers or gangrene in the lower extremity. Diagnostic imaging is crucial for
evaluation and management of CLI. Currently, digital subtraction angiography is
the established modality for evaluating CLI. However, digital subtraction
angiography is invasive and carries a risk of complications. Non-invasive
imaging modalities such as computed tomography angiography (CTA) and magnetic
resonance angiography (MRA) have a high diagnostic accuracy for assessment of
lower extremity arterial disease in patients with claudication, but have not
been thoroughly evaluated in patients with CLI. Also, there are no head-to-head
comparisons of CTA and MRA in patients with CLI. Performing a direct comparison
of CTA and MRA with digital subtraction angiography brings practical and
ethical challenges, because of the burden for the patient. Therefore, we will
first perform a feasibility study to assess the feasibility of a larger study,
which would compare the diagnostic performance of CTA and MRA with digital
subtraction angiography as reference standard.

The main objective of this pilot study is to evaluate the burden of an
additional CTA and MRA procedure in patients, and to evaluate the quality of
the CTA and MRA protocols.

The study is a cross-sectional feasibility study to determine the burden of CTA
and MRA. It is also a preliminary study of the diagnostic accuracy of CTA and
MRA that is used to guide a future larger diagnostic study. All included
patients will be evaluated with CTA, MRA and digital subtraction angiography.
Since the interventional radiologist may perform interventions during digital
subtraction angiography, both CTA and MRA will be performed before digital
subtraction angiography. All imaging procedures will be performed within seven
days. There are no restrictions as to which imaging modality, CTA or MRA is
performed first.

Participation to this study will not be beneficial for the patient. The patient
will be exposed to 12 mSv radiation from the CTA procedure, which gives an
additional risk for cancer. See appendix 8 for the advice on radiation
exposure. Furthermore, for both the CTA and MRA procedure contrast will be
given, respectively iodinated contrast and gadolinium. For iodinated contrast
media the most common adverse reactions are nausea, feeling of pain or heat,
and headache. These occur in less than 1% of the patients. Other, more severe
adverse reactions are allergic reactions and contrast induced nephropathy. See
appendix 9 for the summary of product characteristics of Ultravist.
The most common adverse reactions of gadolinium are headache, dizziness, taste
disorders, numb and tingling feeling, vascular dilation, nausea and pain or
reactions at the site of puncture. These occur in less than 1% of the patients.
The risk for nephrogenic systemic fibrosis will be minimal, since patients with
renal failure are excluded from this trial. See appendix 10 for the summary of
product characteristics of Gadovist.
The burden of the patients according to the standard procedures of this
hospital account for both the CTA and MRA procedure, since primary imaging is
performed using DUS. However, several hospitals in the Netherlands, e.g. Leiden
University Medical Center and Erasmus Medical Center Rotterdam, perform a CTA
in patients with CLI before referring for DSA. In these hospitals, this study
would imply only an additional burden of just one modality, i.e. MRA.
Until now, the vast majority of patients included in comparative diagnostic
studies of CTA and MRA had complaints of IC, and not CLI. As explained in
chapter 3, patients with IC and CLI differ on many aspects, such as location
and severity of disease. As a consequence, imaging recommendation for IC is
not automatically valid for CLI. Adequate recommendations are therefore
difficult considering which imaging modality to perform in patients with CLI.
To perform an adequate comparison between CTA and MRA in patients with CLI, and
to find an adequate replacement for the diagnostic DSA, we believe the only
adequate way is to perform the CTA and MRA in the same patient. Before
performing such a study, we first have to assess its feasibility since we
realize that undergoing both CTA and MRA is hard for these patients. Therefore,
we first have to perform a study to assess the patients* burden, the quality of
our CTA and MRA protocols and the inclusion rate of patients.