Lower-Limb Adventitial Infusion of DexaMethasone Via Bullfrog to Reduce Occurrence of Restenosis After Atherectomy (ATX)-Based Revascularization

This is a prospective, multi-center, randomized pilot study to document the effects of
adventitial delivery of dexamethasone after atherectomy-based revascularizations of lesions
below the knee in symptomatic patients with critical limb ischemia (CLI). Up to 120 patients
(60 treatment and 60 control), including up to 20 Rutherford 6 patients (10 treatment and 10
control) at up to 30 sites in the United States and Europe. This study will assess the safety
and effectiveness of Bullfrog Micro-Infusion Device adventitial deposition of dexamethasone
in reducing inflammation and restenosis in patients with clinical evidence of chronic
critical limb ischemia with an angiographically significant lesion in the infrapopliteal
crural vessels.

Inclusion Criteria:

Screening Criteria:

- Age ≥18 years

- Patient or patient's legal representative have been informed of the nature of the
study, agrees to participate and has signed an IRB/EC approved consent form

- Female patients of childbearing potential have a negative pregnancy test ≤7 days
before the procedure and are willing to use a reliable method of birth control for the
duration of study participation

- Patient has documented chronic Critical Limb Ischemia (CLI) in the target limb from
the popliteal artery to the ankle joint prior to the study procedure with Rutherford
Category 4, 5 or 6

- Life expectancy >1 year in the Investigator's opinion

Angiographic Criteria:

- Successful revascularization of the TL with less than 30% residual stenosis, run-off
down to the foot and direct in-line flow to any foot wound

- Reference vessel(s) diameter ≥2 mm

- Single or multiple atherosclerotic lesion ≥70% in at least one infrapopliteal crural
target vessel including the tibioperoneal trunk that totals up to 30 cm in length
(with no greater than 5 cm length of contiguous intervening normal artery), with
possible extension into the popliteal artery distal to the center of the knee joint
space (the P3 segment)

Exclusion Criteria:

Screening Criteria:

- Patient unwilling or unlikely to comply with visit schedule

- Planned major index limb amputation

- Active foot infection; however, osteomyelitis in the toes or mild cellulitis around
the perimeter of gangrene or small ulcers are not exclusions, but osteomyelitis of the
metatarsal or more proximal region would be exclusionary

- Inability to receive study medications

- Estimated glomerular filtration rate (eGFR) less than 30 mL/min, except for patients
with end stage renal disease on chronic hemodialysis

- Stage 3 (per SVS WIfI classification) or worse heel ulcers or heel ulcers that are
determined to be primarily neuropathic in nature

Angiographic/Procedural Criteria:

- Hemodynamically significant inflow lesion (≥50% DS) or occlusion in the ipsilateral
iliac, SFA, or popliteal arteries in which there is failure to successfully treat and
obtain a <30% residual stenosis

- Target lesion length is >25 cm as measured from proximal normal vessel to distal
normal vessel

- Total length of lesions treated during the case (including target lesion, inflow
lesions, and other non-target lesions) >25 cm

- Lesions revascularized during the index case but untreated by Bullfrog

- Use of alternative therapy, e.g. radiation therapy, as part of the index lesion
treatment, or use of any drug eluting stents (DES) or drug-eluting balloon/drug-coated
balloons (DEB/DCB) for treatment of any infra-inguinal lesions during the study
procedure or during the initial six-month follow up period

- Previously implanted stent in the TL(s)

- Aneurysm in the target vessel

- Acute thrombus in the target limb

- Failure to cross the TL with a guide wire; however, subintimal wire crossing is
allowed

- Heavy eccentric or concentric calcification at index lesion, which in the judgment of
the investigator would prevent penetration of the Micro-Infusion Device needle through
the vessel wall