Intima Versus Adventitia Drug Delivery to Elucidate Mechanisms of Restenosis: Magnetic Resonance Imaging

Peripheral artery disease (PAD) affects at least 12 million Americans annually with more than
half a million patients undergoing an endovascular or surgical revascularization procedure in
order to treat the disease. Unfortunately, about two-thirds of patients still have blockages
in the leg arteries, even after these procedures.

Advances in Magnetic resonance imaging (MRI) offer promise for understanding the mechanism of
failure through insights into vessel wall composition, remodeling, and inflammation.
Restenosis has a known relationship to inflammation. Advances in micro-catheter technologies
offer the ability to deliver anti-inflammatory medications such as Dexamethasone (DEX)
directly to the adventitia and advances in drug delivery on balloon surfaces to deliver
paclitaxel to the intima of the artery.

This study aims to investigate if patient-specific parameters affect angioplasty outcomes, if
DEX has a biological effect on the vessel wall, and if this effect is through the reduction
of inflammation.

Inclusion Criteria:

Screening:

1. Male or non-pregnant female ≥ 35 years of age

2. Atherosclerotic, infrainguinal PAD

3. Rutherford Clinical Category 2-6

4. Stenosis detected by radiology that in the clinician's opinion is the reason for the
PAD symptoms

5. Patient is willing to provide informed consent and comply with the required follow up
visits, testing schedule, and medication regimen

6. Estimated Glomerular Filtration Rate (eGFR) ≥ 30 and/or threshold established by the
local Institutional Review Board or Committee of Human Research

Procedural Criteria:

1. De novo atherosclerotic lesion qualifying for angioplasty

2. A patent artery proximal to the index lesion. Concomitant inflow procedures, including
open femoral artery endarterectomy and/or stenting of the iliac arteries, are
permissible.

3. >50% diameter stenosis of the superficial femoral artery and/or popliteal artery
(between the profunda and tibioperoneal trunk)

4. Reference vessel diameter ≥3 mm and ≤ 8mm

5. Successful wire crossing of lesion

6. Successful angioplasty of the index lesion or part of the index lesion, defined as
≤30% residual lumen stenosis compared with adjacent non-diseased lumen diameter,
without flow-limiting dissection

Exclusion Criteria:

Screening Criteria:

1. Any contraindication to receiving an MRI

2. Pregnant, nursing, or planning on becoming pregnant in < 2yrs

3. Life expectancy of < 1 yr

4. History of solid organ transplantation

5. Patient actively participating in another investigational device or drug study

6. History of hemorrhagic stroke within 3 months of index procedure

7. Previous or planned surgical or interventional procedure within 30 days of index
procedure

8. Chronic renal insufficiency with eGFR < 30

9. Prior bypass surgery, stenting, atherectomy or angioplasty of the index lesion

10. Inability to take required study medications

11. Contra-indication or known hypersensitivity to dexamethasone sodium phosphate,
contrast media, gadolinium, aspirin or Plavix

12. Systemic fungal infection

13. Acute limb ischemia

14. Prior participation of the index limb in the current study (contralateral treatment is
allowed)

15. Patient is being treated with long-term steroids (not including treatment of a
bronchial condition with inhaled steroids)

Procedural Criteria:

1. Index lesions extending into the tibial trifurcation or above the profunda. Note: the
outflow tibial artery can be treated concomitantly. Similarly, the common femoral
artery can be treated concomitantly, either with open endarterectomy and patch
angioplasty or with endovascular methods. However, the index lesion cannot be
contiguous with either the CFA or the tibial trifurcation.

2. Circumferential calcification at index lesion, which in the judgment of the
investigator would prevent penetration of the Micro-Infusion catheter needle through
the vessel wall

3. Inadequate distal outflow defined as no patent tibial arteries (>50% stenosis). The
outflow vessel can be established at the time of primary treatment

4. Use of adjunctive therapies other than angioplasty. Chocolate balloons and/or scoring
balloons are allowed, if used below reference diameter.