Clinical trial NCT02807779: Intima Versus Adventitia Drug Delivery to Elucidate Mechanisms of Restenosis: Magnetic Resonance Imaging
Official title: Intima Versus Adventitia Drug Delivery to Elucidate Mechanisms of Restenosis: Magnetic Resonance Imaging
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Peripheral Artery Disease
Vascular Disease
Critical Limb Ischemia
Keywords: angioplasty
peripheral artery disease
peripheral vascular disease
atherosclerosis
balloon angioplasty
dexamethasone
drug coated balloon
paclitaxel
walking
claudication
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: University of Washington
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2016-06-21
Enrollment: 33
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This is a prospective, multicenter, randomized trial to determine the mechanisms of vascular healing. The study will evaluate subjects with peripheral artery disease (PAD) who require an endovascular intervention of the femoro-popliteal (SFA) artery to restore blood flow to the leg.

Detailed description: 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.

In response to an FDA issued "Letter to Healthcare Providers" dated August 9, 2019 that reported the "relative risk for increased mortality at 5 years was 1.57 (95% confidence interval 1.16 - 2.13), which corresponds to a 57% relative increase in mortality in patients treated with paclitaxel-coated devices," participant enrollment in the paclitaxel drug coated balloon arm was stopped and a plain balloon angioplasty arm was added to the protocol.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Percent Wall Volume (PWV)
timeFrame: From Post-Operative Day One to 12 Months
Secondary outcomes:
measure: Change in wall volume (WV) without a change in total vessel volume (TVV)
timeFrame: From Post-Operative Day One to 12 Months
measure: Change in perioperative inflammatory profile (MCP-1)
timeFrame: From Post-Operative Day One to 12 Months
measure: Change in perioperative inflammatory profile (CRP)
timeFrame: From Post-Operative Day One to 12 Months
measure: Change in perioperative inflammatory profile (IL-1beta)
timeFrame: From Post-Operative Day One to 12 Months
measure: Change in ktrans
timeFrame: From 1 Month to 6 Months
measure: Change in lumen volume (LV) relative to total vessel volume (TVV)
timeFrame: From Post-Operative Day One to 12 Months
measure: Percentage of subjects with clinically significant restenosis that undergo reintervention of greater than or equal to 75% of the treated segment
timeFrame: From Post-Operative Day One to 12 Months
Other outcomes:
measure: Extended Clinical Adverse Events Monitoring
timeFrame: From Post-Operative Day One to 36 Months
Locations:
city: San Francisco
country: United States
facility: San Francisco VA Medical Center
state: California
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: San Francisco VA Medical Center
name: Warren Gasper, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: San Francisco VA Medical Center
name: David Saloner, PhD
role: PRINCIPAL_INVESTIGATOR
References: