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

• Sponsor: University of California, San Francisco
• Collaborators: University of Washington; National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): University of California, San Francisco

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Peripheral Artery Disease; Vascular Disease; Critical Limb Ischemia	Drug: Dexamethasone infusion; Device: Drug coated balloon	Phase 4

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	80 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Basic Science
Official Title:	Intima Versus Adventitia Drug Delivery to Elucidate Mechanisms of Restenosis: Magnetic Resonance Imaging
Study Start Date :	August 2015
Estimated Primary Completion Date :	August 2019
Estimated Study Completion Date :	August 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dexamethasone; Patients randomized to the Dexamethasone group will receive dexamethasone infusion to the adventitia of the artery following plain-old-balloon-angioplasty (POBA).	Drug: Dexamethasone infusion; Patients will receive dexamethasone infusion following plain balloon angioplasty; Other Name: microinfusion catheter
Active Comparator: Drug Coated Balloon; Patients 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; Patients will receive angioplasty with a drug-coated balloon following plain balloon angioplasty

Outcome Measures

Primary Outcome Measures :

1. Change in Percent Wall Volume (PWV) [ Time Frame: From Post-Operative Day One to 12 Months ]
   Percent Wall Volume (PWV) of the treated segment of artery will be measured by MRI.

Secondary Outcome Measures :

1. Change in wall volume (WV) without a change in total vessel volume (TVV) [ Time Frame: From Post-Operative Day One to 12 Months ]
   As measured by MRI
2. Change in perioperative inflammatory profile (MCP-1) [ Time Frame: From Post-Operative Day One to 12 Months ]
   As measured by serum MCP-1
3. Change in perioperative inflammatory profile (CRP) [ Time Frame: From Post-Operative Day One to 12 Months ]
   As measured by serum CRP
4. Change in perioperative inflammatory profile (IL-1beta) [ Time Frame: From Post-Operative Day One to 12 Months ]
   As measured by serum IL-1beta
5. Change in ktrans [ Time Frame: From 1 Month to 6 Months ]
   As measured by MRI
6. Change in lumen volume (LV) relative to total vessel volume (TVV) [ Time Frame: From Post-Operative Day One to 12 Months ]
   As measured by MRI

Eligibility Criteria

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Ages Eligible for Study:	35 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Contacts

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Contact: Sukaynah Khetani	415-353-4368	Sukaynah.khetani@ucsf.edu
Contact: David Cheng	415-750-2115 ext 24708	David.cheng4@va.gov

Locations

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United States, California
San Francisco VA Medical Center	Recruiting
San Francisco, California, United States, 94121
Contact: Sukaynah Khetani 415-353-4368 sukaynah.khetani@ucsf.edu
Contact: David Cheng 415-750-2115 ext 24708 david.cheng4@va.gov
Principal Investigator: Warren Gasper, MD
Principal Investigator: David Saloner, PhD
United States, Washington
University of Washington	Recruiting
Seattle, Washington, United States, 98104
Contact: Kristi Pimentel 206-616-2023 kristidb@uw.edu
Principal Investigator: Thomas Hatsukami, MD

Sponsors and Collaborators

University of California, San Francisco

University of Washington

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

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Principal Investigator:	Warren Gasper, MD	San Francisco VA Medical Center
Principal Investigator:	David Saloner, PhD	San Francisco VA Medical Center

More Information

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Responsible Party:	University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT02807779 History of Changes
Other Study ID Numbers:	15-17251; 1R01HL128816-01 ( U.S. NIH Grant/Contract )
First Posted:	June 21, 2016
Last Update Posted:	December 8, 2017
Last Verified:	December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:		Yes

Keywords provided by University of California, San Francisco:

angioplasty; peripheral artery disease; peripheral vascular disease; atherosclerosis; balloon angioplasty	dexamethasone; drug coated balloon; paclitaxel; walking; claudication

Additional relevant MeSH terms:

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Ischemia; Vascular Diseases; Peripheral Arterial Disease; Pathologic Processes; Cardiovascular Diseases; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Dexamethasone; Dexamethasone acetate; BB 1101; Anti-Inflammatory Agents	Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action