Clinical validation of non-invasive tissue perfusion measurements in Vascular diseased patients with PeriFlux 6000 Enhanced Perfusion and Oxygen Saturation (EPOS) system * Pilot study

Peripheral arterial disease (PAD) of the lower extremity is a progressive and
common disease. Symptoms of PAD include pain during exercise, which can
progress into chronic limb-threatening ischemia (CLTI) with pain at rest and
development of non-healing ulcers. PAD and CLTI are the result of impaired
tissue perfusion. To determine the severity of PAD, and localize ischemic
tissue, tissue perfusion measurements are deemed necessary. Most diagnostic
techniques used to establish the diagnosis of PAD can only detect stenotic
lesions of the major arteries, and do not measure real tissue perfusion.
Several CE-marked, non-invasive measurement techniques are available to detect
tissue perfusion, but none of them has been used in the entire peri-procedural
phase of PAD patients who undergo revascularisation of the lower extremity.
Changes in tissue perfusion pre-, per-, post-revascularisation may be important
to evaluate the clinical success of the interventions. Transcutaneous partial
pressure of oxygen (TcPO2) is one of the most often used tissue perfusion
techniques, but with low quality of evidence and several limitations. For
example this method is operator dependent, time consuming, and not suited for
everyday clinical use. This pilot study investigates the use of a new
non-invasive modality that has the potential to increase the accuracy of
determination of tissue perfusion. The Periflux 6000 Enhanced Perfusion and
Oxygen Saturation (EPOS; Perimed AB, Järfälla, Stockholm, Sweden) system is a
non-invasive technique which integrates the use of laser Doppler flowmetry
(LDF) and diffuse reflectance spectroscopy (DRS) for the measurement of both
blood flow and oxygen saturation of the microcirculation. Compared to other
imaging modalities for determination of tissue perfusion, like TcPO2, EPOS may
quantify severity of impaired tissue perfusion and localize regions of impaired
perfusion more accurately. An advantage of this system is the combination of
DRS with LDF that not only measures hemoglobin oxygen saturation, but also the
speed resolved RBC perfusion separated in three speed regions. Therefore, it
has potential as non-invasive diagnostic modality to determine indication for
treatment and to determine treatment success after endovascular
revascularisation procedures.

This pilot study aims to investigate the feasibility and clinical performance
of tissue perfusion measurements with EPOS in the feet/legs in healthy
volunteers and patients with PAD. The EPOS system has not yet been CE approved,
and has not been applied in clinical care. This pilot study aims to investigate
the feasibility and clinical performance of tissue perfusion measurements with
EPOS in the feet in 10 healthy volunteers, 10 claudicants, and 10 patients with
chronic limb-threatening disease and to develop a standardized measurement
protocol for EPOS measurements.

This study is a single center pilot study to investigate the feasibility and
clinical performance of EPOS measurements in 10 healthy volunteers, 10
claudicants, and 10 patients with chronic limb-threatening disease. The tissue
perfusion is measured with EPOS and TcPO2 at three different locations: plantar
and dorsal surface of the foot, and gastrocnemius muscle. Local skin
temperature, systemic blood pressure, and arterial oxygen saturation with a
pulseoximeter are also determined. Claudicants will be measured before
supervised exercise, and patients with chronic limb-threatening disease will be
measured before and after endovascular revascularization. All subjects will be
measured at one leg; for patients the most affected leg. For healthy volunteers
the choice of leg will be at random. This is an observational study and the
patients will receive diagnostics and treatment according to standard of care,
which will not be affected by the study results.

There is very limited risk associated with participation in this study. The
EPOS system is a non-invasive measurement technique which consists of the CE
approved PF6001 main unit (Perimed, Järfälla, Stockholm, Sweden), including the
CE-marked PF6010 LDPM/heat. The non-CE-marked PF6060 spectroscopy unit will be
connected to the patient only via optical fibers and a non-CE approved EPOS
probe that integrates the diffuse reflectance spectroscopy and laser doppler
flowmetry. The Periflux 6000 EPOS system has been approved by the MMAC, and the
study will be submitted by Perimed to the IGJ after approval of this study by
the METC. TcPO2 will be measured with the PF 6040 TcPO2 unit which is a
CE-approved device and will be used in this study according to intended use.
Other measurements (systemic blood pressure, local skin temperature, oxygen
saturation) are routine clinical measurements, with no additional risks. The
burden for the participating healthy volunteers and patients consists of one or
two additional measurement sessions of 130 minutes, which will be scheduled
after regular care appointment when possible. Healthy volunteers and
claudicants will undergo one session of 130 minutes. Patients with CLTI will be
measured in 2 sessions, before and after endovascular revascularization. The
EPOS probe has minor risk of local skin burn, as it can heat up the skin to
44°C, which is identical to the CE-approved and commercially available PF 6040
TcPO2 and PF 6010 LDPM/Heat units. This is included in the risk assessment of
Perimed, which is attached to this protocol. The study results will not affect
diagnostics or treatment of the patients. There are no direct benefits for
participating patients concerning the treatment they are receiving, as this
study is an observational pilot study.