Pivotal Trial of a Novel Paclitaxel-Coated Percutaneous Angioplasty Balloon (ILLUMENATE)

ILLUMENATE Pivotal: ProspectIve, Randomized, SingLe-Blind, U.S. MuLti-Center Study to EvalUate TreatMent of Obstructive SupErficial Femoral Artery or Popliteal LesioNs With A Novel PacliTaxel-CoatEd Percutaneous Angioplasty Balloon

This study is designed to evaluate the safety and efficacy of a Paclitaxel-coated percutaneous transluminal angioplasty (PTA) Catheter in the treatment of patients with peripheral arterial disease.

Study Overview

• Status: Completed
• Conditions: Peripheral Arterial Disease
• Intervention / Treatment: Device: EverCross Percutaneous Transluminal Balloon Catheter; Device: Cardiovascular Ingenuity (CVI) Paclitaxel-coated Percutaneous Transluminal Angioplasty Balloon Catheter

Detailed Description

The ILLUMENATE Pivotal study is a prospective, randomized, multi-center, single-blind study which will include up to 360 subjects in approximately forty-five (45) sites across the United States to evaluate the CVI Paclitaxel-coated PTA Catheter compared to the bare percutaneous transluminal angioplasty balloon catheter (bare balloon catheter) for the treatment of de-novo or post-PTA occluded/stenotic or reoccluded/restenotic (except for in-stent) SFA and/or popliteal arteries.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria
    • LKH Univ. - Klinikum Graz
  • Vienna, Austria
    • Hanusch Krankenhaus Wien
• United States
  • Arizona
    • Yuma, Arizona, United States, 85364
      • Yuma Regional Medical Center
  • California
    • Fremont, California, United States, 94538
      • Mission Cardiovascular Research Institute
    • Los Angeles, California, United States, 90017
      • Good Samaritan Hospital - Los Angeles
  • Colorado
    • Loveland, Colorado, United States, 80538
      • Medical Center of the Rockies
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School of Medicine
  • Florida
    • Gainesville, Florida, United States, 32605
      • Cardiovascular Research of North Florida
    • Miami, Florida, United States, 33176
      • Baptist Cardiac and Vascular Institute
    • Pensacola, Florida, United States, 32504
      • Coastal Vascular and Interventional
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
  • Illinois
    • Oakbrook Terrace, Illinois, United States, 60181
      • Advocate Health and Hospitals Corporation
  • Indiana
    • Fort Wayne, Indiana, United States, 46802
      • St. Joseph Hospital
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • Central Iowa Hospital Corporation
  • Michigan
    • Petoskey, Michigan, United States, 49770
      • Cardiac & Vascular Research Center of Northern Michigan
    • Wyoming, Michigan, United States, 15146
      • Metro Health Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Jackson Heart Clinic
  • New Jersey
    • Browns Mills, New Jersey, United States, 08015
      • Deborah Heart and Lung Center
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital
    • Raleigh, North Carolina, United States, 27607
      • Rex Hospital
    • Raleigh, North Carolina, United States, 27607
      • Wake Heart Research
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43214
      • OhioHealth Research Institute
    • Elyria, Ohio, United States, 44035
      • North Ohio Research LTD.
    • Toledo, Ohio, United States, 43606
      • Jobst Vascular Institute
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Oklahoma Foundation for Cardiovascular Research
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence Heart and Vascular Institute
  • Pennsylvania
    • Beaver, Pennsylvania, United States, 15009
      • Heritage Valley Health System
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
    • Wormleysburg, Pennsylvania, United States, 17043
      • Pinnacle Health Cardiovascular Institute, INC.
  • South Carolina
    • Columbia, South Carolina, United States, 29204
      • Providence Cardiology LLC
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117
      • Sanford Health Vascular Associates
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • University Surgical Associates
    • Kingsport, Tennessee, United States, 37660
      • Wellmont Holston Area Medical Center
    • Knoxville, Tennessee, United States, 37909
      • Premier Surgical Associates
  • Texas
    • Dallas, Texas, United States, 75231
      • Texas Health & Research Education Institution
    • El Paso, Texas, United States, 79902
      • El Paso Cardiology Associates
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Vascular Specialist
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • CAMC Clinical Trial Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Health Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with symptomatic leg ischemia, requiring treatment of the Superficial Femoral Artery (SFA) or popliteal artery.

Exclusion Criteria:

• Known intolerance to study medications, paclitaxel or contrast agents that in the opinion of the investigator cannot be adequately pre-treated

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bare PTA; The control device is a commercially available PTA balloon catheter (EverCross™ 0.035 PTA Balloon Catheter, Covidien, Plymouth, MN 55441, USA).	Device: EverCross Percutaneous Transluminal Balloon Catheter; The control device is a commercially available PTA balloon catheter (EverCross™ 0.035 PTA Balloon Catheter, Covidien, Plymouth, MN 55441, USA).
Experimental: Drug-Coated PTA; The CVI Paclitaxel-coated PTA Catheter is a commercially available PTA balloon catheter (EverCross™ 0.035 PTA Balloon Catheter, Covidien, Plymouth, MN 55441, USA) coated with paclitaxel using a proprietary carrier.	Device: Cardiovascular Ingenuity (CVI) Paclitaxel-coated Percutaneous Transluminal Angioplasty Balloon Catheter; The CVI Paclitaxel-coated PTA Catheter is a commercially available PTA balloon catheter (EverCross™ 0.035 PTA Balloon Catheter, Covidien, Plymouth, MN 55441, USA) coated with paclitaxel using a proprietary carrier.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patency at 12 Month Post-procedure	Patency is defined as the absence of target lesion restenosis as determined by duplex ultrasound (Peak Systolic Velocity Ratio (PSVR) ≤ 2.5) and freedom from clinically-driven target lesion revascularization.	12 months
Freedom From Device and Procedure-related Death and Target Limb Major Amputation and Clinically-driven Target Lesion Revascularization	Freedom from device and procedure-related death through 30 days post-procedure and freedom from target limb major amputation and clinically-driven target lesion revascularization through 12 months post-procedure.	30 Days and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Adverse Event (MAE) Rate in the Hospital and at 1, 6, 12, 24, 36, 48 and 60 Months Post-procedure	Major adverse event (MAE) rate in the hospital and at 1, 6, 12, 24, 36, 48 and 60 months post-procedure, defined as a composite rate of cardiovascular death, target limb major amputation and clinically-driven target lesion revascularization (TLR).	1, 6, 12, 24, 36, 48 and 60 months
Rate of Vascular Access and Bleeding Complications	Rate of vascular access and bleeding complications in the hospital and at 1, 6, 12 and 24 months.	in-hospital and 1, 6, 12 and 24 months
Rate of Clinically-driven Target Lesion Revascularization		6, 12, 24, 36, 48 and 60 months
Rate of Target Lesion Revascularization		6, 12, 24, 36, 48 and 60 months
Rate of Target Limb Major Amputation		1, 6, 12, 24, 36, 48 and 60 months
Mortality Rate		6, 12, 24, 36, 48 and 60 months
Rate of Occurrence of Arterial Thrombosis of the Treated Segment		1, 6, 12, 24, 36, 48 and 60 months
Patency Rate and Freedom From Clinically-driven TLR	Patency rate defined as the absence of target lesion restenosis as determined by duplex ultrasound (PSVR ≤ 2.5) and freedom from clinically-driven TLR at 6, 24 and 36 months	6, 24 and 36 months
Lesion Success of Achieving a Final In-lesion Residual Diameter Stenosis of ≤50%	Lesion success, defined as achievement of a final in-lesion residual diameter stenosis of ≤50% (as determined by the angiographic core lab), using any device after wire passage through the lesion.	procedure, Day 0
Technical Success of Achieving a Final In-lesion Residual Diameter Stenosis of ≤50%	Technical success, defined as achievement of a final in-lesion residual diameter stenosis of ≤50% (as determined by the angiographic core lab), using the CVI Paclitaxel-coated PTA Catheter or bare balloon catheter without a device malfunction after wire passage through the lesion.	procedure, Day 0
Per Subject Clinical Success Achieving no Major Adverse Events During the Procedure	Clinical success (per subject) defined as technical success without the occurrence of major adverse events during the procedure.	procedure, Day 0
Per Subject Procedural Success Achieving no Major Adverse Events During the Procedure	Procedural success (per subject) defined as lesion success without the occurrence of major adverse events during the procedure.	procedure, Day 0
Change in Ankle-brachial Index (ABI) From Pre-procedure	Subjects who had reinterventions were included in ABI analyses so some improvements may be reflective of revascularizations during the follow-up period.	6, 12, 24 and 36 months

Collaborators and Investigators

• Sponsor: Spectranetics Corporation
• Investigators: Principal Investigator: Prakash Krishnan, MD, Mt. Sinai Medical Center

Publications and helpful links

General Publications

• Gray WA, Jaff MR, Parikh SA, Ansel GM, Brodmann M, Krishnan P, Razavi MK, Vermassen F, Zeller T, White R, Ouriel K, Adelman MA, Lyden SP. Mortality Assessment of Paclitaxel-Coated Balloons: Patient-Level Meta-Analysis of the ILLUMENATE Clinical Program at 3 Years. Circulation. 2019 Oct;140(14):1145-1155. doi: 10.1161/CIRCULATIONAHA.119.040518. Epub 2019 Sep 30.
• Lyden SP, Brodmann M, Parikh SA, Krishnan P, Schroeder H, Werner M, Holden A, Ouriel K, Tarra T, Gray WA. Four-year patient-level pooled mortality analysis of the ILLUMENATE US Pivotal and EU randomized controlled trials. J Vasc Surg. 2022 Feb;75(2):600-607. doi: 10.1016/j.jvs.2021.07.244. Epub 2021 Sep 8.
• Krishnan P, Faries P, Niazi K, Jain A, Sachar R, Bachinsky WB, Cardenas J, Werner M, Brodmann M, Mustapha JA, Mena-Hurtado C, Jaff MR, Holden AH, Lyden SP. Stellarex Drug-Coated Balloon for Treatment of Femoropopliteal Disease: Twelve-Month Outcomes From the Randomized ILLUMENATE Pivotal and Pharmacokinetic Studies. Circulation. 2017 Sep 19;136(12):1102-1113. doi: 10.1161/CIRCULATIONAHA.117.028893. Epub 2017 Jul 20.

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2013
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): March 19, 2018

Study Registration Dates

• First Submitted: May 8, 2013
• First Submitted That Met QC Criteria: May 20, 2013
• First Posted (Estimate): May 21, 2013

Study Record Updates

• Last Update Posted (Actual): August 24, 2020
• Last Update Submitted That Met QC Criteria: August 10, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: TP-1397