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

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.

Study Overview

• Status: Completed
• Conditions: Peripheral Artery Disease; Critical Limb Ischemia; Vascular Disease
• Intervention / Treatment: Drug: Dexamethasone infusion; Device: Drug coated balloon; Device: Plain balloon angioplasty

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94121
      • San Francisco VA Medical Center
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dexamethasone; Participants randomized to the Dexamethasone group will receive dexamethasone infusion to the adventitia of the artery following plain-old-balloon-angioplasty (POBA).	Drug: Dexamethasone infusion; Participants will receive dexamethasone infusion following plain balloon angioplasty; Other Names: microinfusion catheter
Active Comparator: 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.	Device: Drug coated balloon; Participants will receive angioplasty with a drug-coated balloon following plain balloon angioplasty
Active Comparator: 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.	Device: Plain balloon angioplasty; Participants will receive plain balloon angioplasty only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Percent Wall Volume (PWV)	The change in percent wall volume (PWV) of the treated segment between the postoperative and 12 month time points as measured by MRI	From Post-Operative Day One to 12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Wall Volume (WV) Without a Change in Total Vessel Volume (TVV)	The change in wall volume (WV) without change in total vessel volume (TVV) of the treated segment between the postoperative and 12 month time points as measured by MRI	From Post-Operative Day One to 12 Months
Change in Perioperative Inflammatory Profile (MCP-1)	The serum concentration of monocyte chemoattractant protein-1 (MCP-1) between postprocedure day 1 and 12 months postprocedure. Reported as the area under the curve (AUC) of the MCP-1 concentration (postprocedure day 1, 1 month and 12 months)	From Post-Operative Day One to 12 Months
Change in Perioperative Inflammatory Profile (CRP)	The serum concentration of C-reactive protein (CRP) between postprocedure day 1 and 12 months postprocedure. Reported as the area under the curve (AUC) of the CRP concentration (postprocedure day 1, 1 month and 12 months).	From Post-Operative Day One to 12 Months
Change in Perioperative Inflammatory Profile (IL-1beta)	The serum concentration of interleukin-1beta (IL-1beta) between postprocedure day 1 and 12 months postprocedure. Reported as the area under the curve (AUC) of the IL-1beta concentration (postprocedure day 1, 1 month and 12 months).	From Post-Operative Day One to 12 Months
Change in Transfer Constant (Ktrans)	The change in adventitial transfer constant (Ktrans) of the treated segment between the postoperative and 6 month time points as measured by dynamic contrast enhanced MRI	From 1 Month to 6 Months
Change in Lumen Volume (LV) Relative to Total Vessel Volume (TVV)	The change in lumen volume (LV) relative to total vessel volume (TVV) of the treated segment between the postoperative and 12 month time points as measured by MRI	From Post-Operative Day One to 12 Months
Percentage of Subjects With Clinically Significant Restenosis That Undergo Reintervention of Greater Than or Equal to 75% of the Treated Segment	Percentage of subjects with clinically significant restenosis that undergo reintervention of greater than or equal to 75% of the treated segment by the 12 month timepoint.	From Post-Operative Day One to 12 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extended Clinical Adverse Events Monitoring	Participant monitoring for clinical adverse events	From Post-Operative Day One to 36 Months

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); University of Washington
• Investigators: Principal Investigator: Warren Gasper, MD, San Francisco VA Medical Center; Principal Investigator: David Saloner, PhD, San Francisco VA Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2016
• Primary Completion (Actual): October 31, 2020
• Study Completion (Actual): October 31, 2022

Study Registration Dates

• First Submitted: April 1, 2016
• First Submitted That Met QC Criteria: June 16, 2016
• First Posted (Estimated): June 21, 2016

Study Record Updates

• Last Update Posted (Actual): July 17, 2025
• Last Update Submitted That Met QC Criteria: June 27, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: paclitaxel; atherosclerosis; walking; balloon angioplasty; dexamethasone; claudication; peripheral artery disease; angioplasty; peripheral vascular disease; drug coated balloon
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Ischemia; Chronic Limb-Threatening Ischemia; Vascular Diseases; Peripheral Arterial Disease; Antineoplastic Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: 15-17251; 1R01HL128816-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No