ArteriaL Fluorescence Angiography for Peripheral Arterial Disease (ALFAPAD) Study

In Peripheral Arterial Disease (PAD), macrovascular lesions cause a change in
haemodynamics in the lower limbs, reducing distal perfusion pressure. The
microcirculation and nutrient blood flow to tissue becomes severely impaired,
ultimately resulting in critical limb ischemia (CLI) and accompanying symptoms
such as ischemic rest pain or non-healing wounds. For patients with CLI, the
prognosis of the leg is strongly limited unless successful revascularization is
performed. In most cases, the first choice of invasive treatment is
Percutaneous Transluminal Angioplasty (PTA), possibly supplemented with the
placement of a stent. The currently employed imaging techniques are not
applicable for assessment of the microcirculation in the foot, even though the
procedure is aimed at improving this very matter. A second imaging/assessment
module should be introduced that can visualise the microcirculation of the
foot. It should be able to assess the effect of the endovascular treatment
during the procedure and eventually predict clinical outcome.

In this study, fluorescence angiography (FA) will be used to assess the
perfusion of the plantar side of the foot. FA uses near-infrared light in
combination with a fluorescent dye, indocyanine green (ICG), to image blood
flow in tissue. During FA, ICG is generally administered intravenously. The
endovascular sheath used during PTA, however, allows an alternative arterial
injection (ALFA), which should theoretically lead to improved images with
greater discriminatory power and higher repeatability.
The rationale of this research is to determine whether peroperative ALFA can be
used to objectively measure perfusion and tissue characteristics during a
revascularization procedure. This pilot study should indicate whether further
investigations are meaningful, and how quantitative analysis of ALFA images
should be performed.

Primary Objective:
1. To determine the feasibility and clinical relevance of quantifiable
parameters from intraoperative ALFA-measurements.

Secondary Objective(s):
1. Determine the intraoperative applicability of ALFA.
2. Determine the effect of revascularization on the defined parameters.
3. Determine the ability of these parameters to predict clinical outcome.
4. Determine the added value of post-operative intravenous FA measurements, as
well as their relation to intraoperative ALFA.

This pilot study will be organised as a prospective observational
surgeon-blinded single centre (MST Enschede) cohort study. In this case,
surgeon-blinded means that the operating surgeon cannot observe the ALFA
images, to ensure that they do not alter their operative strategy based on this
study.

Patients will undergo the following course of actions:
1. In the outpatient clinic, after having agreed to perform surgery based on
shared decision-making, the surgeon will provide information (including PIF) on
the study and asks whether the patient would be willing to participate. While
patients are free to formally decline at this point, agreement will be noted as
*preliminary*.
2. The evening/morning before the surgery, the clinical researcher will
formalize the patient*s agreement to participate by gaining written informed
consent.
3. During the operation, ALFA measurements by intra-arterial administration of
ICG (0.01 mg/kg bodyweight) will be performed twice in a standardized fashion.
The first occurs after general anaesthesia has been administered and the
endovascular sheath has been established according to the normal operative
plan. The second measurement will be performed after the surgeon either
finishes or aborts the procedure. The increased duration of the entire
operation is estimated at approximately 2 x 5 = 10 minutes.
4. The day after surgery, patients will undergo a *regular* intravenous FA
measurement (5mg ICG) at the nursing ward. The aim of this is to relate these
measurements to intraoperative ALFA measurements and to investigate the use of
intravenous FA as an imaging tool to be used in clinical follow-up. To this
end, the standard dosage of 5mg ICG will be injected through a readily present
intravenous catheter.
5. Regular follow-up at nursing ward and outpatient clinic, according to
standard-of-care. Clinical parameters will be extracted from medical
records.

Leaflet of Verdye: ICG has a very low risk profile, with anaphylactic reactions
< 0.01%. Patients with a known increased risk for adverse events as mentioned
in the leaflet will not be included in this study.

Near-infrared imaging using LED is non-ionizing, non-contact and completely
unharmful for patients and users without the need for protective measures.
Users are educated by Karl Storz on the use of the system.

This study is observational and surgeon-blinded, so there are no potential
benefits or risks to be had in regard to operative strategy or clinical
outcome.