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

NCT ID: NCT02807779

Last Updated: 2025-07-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-10
• Study Completion Date: 2022-10-31

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.

Conditions

Peripheral Artery Disease; Vascular Disease; Critical Limb Ischemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Dexamethasone

Participants randomized to the Dexamethasone group will receive dexamethasone infusion to the adventitia of the artery following plain-old-balloon-angioplasty (POBA).

Group Type: EXPERIMENTAL

Dexamethasone infusion

Intervention Type: DRUG

Participants will receive dexamethasone infusion following plain balloon angioplasty

Drug Coated Balloon

Participants randomized to the Drug Coated Balloon (DCB) group will not receive dexamethasone infusion to the adventitia of the artery following (POBA). They will receive additional angioplasty with a paclitaxel coated balloon.

Group Type: ACTIVE_COMPARATOR

Drug coated balloon

Intervention Type: DEVICE

Participants will receive angioplasty with a drug-coated balloon following plain balloon angioplasty

Plain Balloon Angioplasty

Participants randomized to the Plain Balloon Angioplasty will receive balloon angioplasty (POBA) only. They will not receive a dexamethasone infusion to the adventitia or paclitaxel.

Group Type: ACTIVE_COMPARATOR

Plain balloon angioplasty

Intervention Type: DEVICE

Participants will receive plain balloon angioplasty only

Interventions

Dexamethasone infusion

Participants will receive dexamethasone infusion following plain balloon angioplasty

Intervention Type: DRUG

Drug coated balloon

Participants will receive angioplasty with a drug-coated balloon following plain balloon angioplasty

Intervention Type: DEVICE

Plain balloon angioplasty

Participants will receive plain balloon angioplasty only

Intervention Type: DEVICE

Other Intervention Names

microinfusion catheter

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 common femoral artery 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.

• Minimum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Washington

OTHER

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Warren Gasper, MD

Role: PRINCIPAL_INVESTIGATOR

San Francisco VA Medical Center

David Saloner, PhD

Role: PRINCIPAL_INVESTIGATOR

San Francisco VA Medical Center

Locations

San Francisco VA Medical Center

San Francisco, California, United States

University of Washington

Seattle, Washington, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1R01HL128816-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

15-17251

Identifier Type: -

Identifier Source: org_study_id