STELLAREX: ILLUMENATE Global and In-Stent Restenosis (ISR) (ILLUMENATE)

Prospective, Single-Arm, Global Multi-Center Study to Evaluate Treatment of Obstructive Superficial Femoral Artery (SFA) and/or Popliteal Lesions With a Novel Paclitaxel-Coated Percutaneous Angioplasty (PTA) Balloon and in In-Stent Restenosis

Cohort 1: Single-Arm, multicenter study to continue to assess the safety and performance of the Stellarex 035 Drug Coated Balloon (formerly known as the Cardiovascular Ingenuity (CVI) Paclitaxel-Coated PTA Balloon Catheter) in the treatment of de novo or restenotic lesions in the superficial femoral and/or popliteal arteries.

Cohort 2: To evaluate this patient population for treatment of in-stent restenotic lesions.

Study Overview

• Status: Completed
• Conditions: Peripheral Arterial Disease
• Intervention / Treatment: Device: Stellarex 0.035" Over-the-Wire (OTW) drug-coated angioplasty balloon (Stellarex DCB)

Detailed Description

Cohort 1:

The purpose of this single arm study is to continue to assess safety and performance of the Stellarex 035 DCB in the treatment of de novo or restenotic lesions in the superficial femoral (SFA) and/or popliteal arteries.

Cohort 2:

A second cohort is being added to evaluate this patient population for treatment of in-stent restenotic lesions.

Cohort 1:

Prospective, multi-center, single-arm study.

Cohort 2:

Prospective, multi-center, single-arm study compared to a historical control.

Cohort 1:

Follow-up assessments will occur at discharge, 1 month, 6 months, 12 months, 24 months, 36 months, 48 months, and 60 months following the study procedure.

Cohort 2:

Follow-up assessments will occur at discharge, 1 month, 6 months, 12 months, 24 months and 36 months following the study procedure.

• Study Type: Interventional
• Enrollment (Actual): 499
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Auchenflower, Australia
    • The Wesley St. Andrew Research Institute Ltd.
  • Bedford, Australia
    • Flinders Medical Centre
  • Brisbane, Australia
    • Royal Brisbane and Women's Hospital
  • Dandenong, Australia, 3175
    • Monash Medical Centre at Dandenong Campus
  • Melbourne, Australia
    • The Alfred Hospital
  • Nedlands, Australia
    • Sir Charles Gairdner Hospital
• Austria
  • Graz, Austria, 8036
    • Medizinische Universität Graz - Univ. Klinik für Innere Medizin
• Belgium
  • Aalst, Belgium, 9300
    • Onze Lieve Vrouw Ziekenhuis
  • Antwerpen, Belgium
    • Middelheim Hospital
  • Bonheiden, Belgium, 2820
    • Imelda Hospital
  • Dendermonde, Belgium, 9200
    • AZ Sint-Blasius
  • Genk, Belgium, 3600
    • ZOL Campus Sint Jan
  • Gent, Belgium
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium
    • University Clinic Leuven
  • Tienen, Belgium
    • Regionaal Ziekenhuis Heilig Hart Tienen, Campus Mariëndal - MCT, Vascular Surgery Department
• France
  • Clermont-Ferrand, France
    • CHU de Clermont-Ferrand, Hôpital Gabriel Montpied
  • Lyon, France
    • CHU de Lyon, Hôpital Edouard Herriot
  • Marseille, France
    • Hopital de Ia Timone
  • Nantes, France
    • CHU de Nantes, Hôpital Nord Laennec
  • Paris, France
    • Hopital Europeen Georges Pompidou
  • Rennes, France
    • CHU de Rennes, Hopital Pontchaillou
  • Toulouse, France
    • Clinique Pasteur
• Germany
  • Bad Krozingen, Germany
    • Universitäts-Herzzentrum Freiburg - Bad Krozingen
  • Berlin, Germany, 3347
    • Jüdisches Krankenhaus Berlin
  • Heidelberg, Germany
    • Medizinische Universitätsklinik III
  • Immenstadt, Germany
    • Klinikum Immenstadt, Herz-und Gefässzentrum Oberallgäu-Kempten
  • Langensteinbach, Germany, 76307
    • SRH Klinikum Karlsbad-Langensteinbach
  • Leipzig, Germany
    • University Leipzig Medical Center
  • Rosenheim, Germany, 83022
    • RoMed Klinikum Rosenheim
  • Tübingen, Germany
    • Universitatsklinik, Abteilung Für Diagnostische und Inverventionelle Radiologie
• Italy
  • Ancona, Italy
    • Ospedali Riuniti - SOD
  • Palermo, Italy
    • Villa Maria Eleonora Hospital
  • Perugia, Italy
    • S.C. Chirurgia Vascolare ed Endovascolare
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital
  • Auckland, New Zealand, 2015
    • Middlemore Hospital
  • Hamilton, New Zealand, 3240
    • Waikato Hospital
  • Wellington, New Zealand
    • Wellington Hospital
• Poland
  • Gdańsk, Poland
    • Uniwersyteckie Centrum Kliniczne
  • Warszawa, Poland
    • Instytut Hematologii i Transfuzjologii
• Spain
  • Barcelona, Spain
    • Centre d'Atencio Integral Hospital Dos de Maig
  • Madrid, Spain
    • Hospital Universitario Quiron de Madrid
• United Kingdom
  • London, United Kingdom
    • King's College
  • London, United Kingdom
    • Imperial College Academic and Healthcare NHS Trust, St. Mary's Hospital
  • London, United Kingdom
    • UCL Division of Surgery and Interventional Science

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Cohort 1: General Inclusion Criteria:

1. Has symptomatic leg ischemia, requiring treatment of the SFA and/or popliteal artery.
2. Has a Rutherford Clinical Category of 2 - 4. Note: Rutherford Clinical Category 2 subjects should be entered into the study if conservative treatment has been unsuccessful.
3. Is ≥18 years old.
4. Has life expectancy >1 year.
5. Is able and willing to provide written informed consent prior to study specific procedures.
6. Is willing and capable of complying with the required follow-up visits, testing schedule and medication regimen.

Cohort 1: Angiographic Inclusion Criteria:

1. Has evidence at the target lesion(s) of clinically and hemodynamically significant de novo stenosis or restenosis, or occlusion, in the SFA (1 cm distal to the ostium of the profunda) and/or popliteal artery (proximal to the popliteal trifurcation), confirmed by angiography.
2. Has target limb with at least one patent (<50% stenosis) tibio-peroneal run-off vessel to the foot confirmed by baseline angiography or magnetic resonance angiography (MRA) or computed tomography angiography (CTA). Note: Treatment of outflow disease is NOT permitted.
3. Has 1 or 2 target lesion(s) with a cumulative lesion(s) length of no more than 20 cm. Note: A maximum of two (2) lesions can be treated if the cumulative total lesion length (i.e. the combined length of both lesions) is less than or equal to 20cm.
4. Has target lesion(s) located >2 cm from any stent if the target vessel was previously stented.
5. Has a reference vessel diameter of 4 - 6 mm by visual estimate.
6. Has a successful exchangeable guidewire crossing of the lesion(s).

Cohort 1: General Exclusion Criteria:

1. A female who is pregnant, of childbearing potential not taking adequate contraceptive measures, or nursing; or a male intending to father children during the study.
2. Has significant gastrointestinal bleeding or any coagulopathy that would contraindicate the use of anti-platelet therapy
3. Has known intolerance to study medications, paclitaxel or contrast agents that in the opinion of the investigator cannot be adequately pre-treated.
4. Is currently participating in another investigational device or drug study that would interfere with study endpoints.
5. Has history of hemorrhagic stroke within 3 months.
6. Has surgical or endovascular procedure of the target limb within 14 days prior to the index procedure.
7. Has any planned surgical intervention (requiring hospitalization) or endovascular procedure within 30 days after the index procedure.
8. Has had a previous peripheral bypass affecting the target limb.
9. Has unstable angina pectoris, myocardial infarction, liver failure, renal failure or chronic kidney disease (dialysis dependent, or serum creatinine ≥2.5 mg/dL) within 30 days of the index procedure.

Cohort 1: Angiographic Exclusion Criteria:

1. Has significant stenosis (≥50%) or occlusion of inflow tract that is not successfully revascularized (<30% residual stenosis without death or major vascular complication) prior to treatment of the target lesion(s). Only treatment of target lesion(s) is acceptable after successful treatment of inflow iliac artery lesion(s).
2. Has an acute or sub-acute intraluminal thrombus within the target vessel.
3. Has in-stent restenosis or restenosis of the target lesion following previous treatment with a drug-coated balloon.
4. Has an aneurysm (at least twice the reference vessel diameter) located in the target vessel, abdominal aorta, iliac, or popliteal arteries.
5. Has perforation, dissection or other injury of the access or target vessel requiring stenting or surgical intervention prior to enrollment.
6. Has no normal arterial segment proximal to the target lesion in which duplex ultrasound velocity ratios can be measured.
7. Requires use of adjunctive therapies (i.e., laser, atherectomy, cryoplasty, scoring/cutting balloons, brachytherapy).
8. Has severe calcification that precludes adequate PTA treatment.

Cohort 2: General Inclusion Criteria:

1. Has symptomatic leg ischemia, requiring treatment of the SFA and/or popliteal artery.
2. Has a Rutherford Clinical Category of 2 - 4. Note: Rutherford Clinical Category 2 subjects should be entered into the study if conservative treatment has been unsuccessful.
3. Is between 18-85 years old.
4. Has life expectancy >1 year.
5. Is able and willing to provide written informed consent prior to study specific procedures.
6. Is willing and capable of complying with the required follow-up visits, testing schedule and medication regimen.
7. History of previous femoropopliteal nitinol stenting which is suspect for in-stent restenosis.
8. The patient has a resting ankle-brachial index (ABI) <0.9 or an abnormal exercise ABI (<0.9) if resting ABI is normal. Patient with incompressible arteries (ABI>1.2) must have a toe-brachial index (TBI) <0.7 in target limb.

Cohort 2: Angiographic Inclusion Criteria:

1. Has angiographic evidence of significant restenosis (≥50% by visual estimate) within a previously deployed femoropopliteal bare nitinol stent(s) including ISR Class I, II or III.
2. Has target limb with at least one patent (<50% stenosis) tibio-peroneal run-off vessel to the foot confirmed by baseline angiography or magnetic resonance angiography (MRA) or computed tomography angiography (CTA). Note: Treatment of outflow disease is NOT permitted.
3. Total target treatment length of in-stent restenosis must be ≥4.0 cm in length and may include a single lesion or a multifocal lesion within the femoropopliteal segment (This includes the proximal, mid, and/or distal SFA and PI, P2 and/or P3 segment of the popliteal artery). Edge restenosis may be treated provided the lesion extends no more than 3 cm outside the margin of the stent (proximal and/or distal margin).
4. Has target lesion(s) located >2 cm from any stent if the target vessel was previously stented.
5. Has a reference vessel diameter of 4 - 6 mm by visual estimate.
6. Has a successful exchangeable guidewire crossing of the lesion(s).

Cohort 2: General Exclusion Criteria:

1. A female who is pregnant, of childbearing potential not taking adequate contraceptive measures, or nursing; or a male intending to father children during the study.
2. Has significant gastrointestinal bleeding or any coagulopathy that would contraindicate the use of anti-platelet therapy.
3. Has known intolerance to study medications, paclitaxel or contrast agents that in the opinion of the investigator cannot be adequately pre-treated.
4. Is currently participating in another investigational device or drug study that would interfere with study endpoints.
5. Has history of hemorrhagic stroke within 3 months including those within <60 days with an unresolved walking impairment.
6. Has surgical or endovascular procedure of the target limb within 3 months prior to the index procedure.
7. Has any planned surgical intervention (requiring hospitalization) or endovascular procedure within 30 days after the index procedure.
8. Has had a previous peripheral bypass affecting the target limb.
9. Has unstable angina pectoris, myocardial infarction within 60 days, liver failure, renal failure or chronic kidney disease (dialysis dependent, or serum creatinine ≥2.5 mg/dL) within 30 days of the index procedure.
10. History of previous femoropopliteal stenting in the target lesion with drug eluting stents or covered stents (endografts).

Cohort 2: Angiographic Exclusion Criteria:

1. Ipsilateral and/or contralateral iliac (or common femoral) artery stenosis

   ≥50% diameter stenosis (DS) that is not successfully treated prior to index procedure (e.g. where a perforation occurred requiring a covered stent) or with final residual stenosis ≥ 30% documented by angiography.

2. Identification of any lesion of the native vessel (excludes ISR) above the target stent in the femoropopliteal segment >50% that is not successfully treated prior to index procedure (e.g. complication requiring additional treatment) or with final residual stenosis >30% documented by angiography. Drug eluting stent (DES) and drug coated balloon (DCB) will not be allowed. The lesion length must be treatable with a single stent (if required). The lesion must not be contiguous with the target lesion; at least 2 cm of normal appearing vessel between the lesion and target lesion/ target stent or between deployed stent (if required) and the target lesion/ target stent.
3. Has an acute or sub-acute intraluminal thrombus within the target vessel.
4. Has an aneurysm (at least twice the reference vessel diameter) located in the target vessel, abdominal aorta, iliac, or popliteal arteries.
5. Has perforation, dissection or other injury of the access or target vessel requiring stenting or surgical intervention prior to enrollment.
6. Has no normal arterial segment proximal to the target lesion in which duplex ultrasound velocity ratios can be measured.
7. Requires use of adjunctive therapies (i.e., laser, atherectomy, cryoplasty, scoring/cutting balloons, brachytherapy).
8. Grade 4 or 5 stent fracture affecting target stent or proximal to the target stent, or where evidence of stent protrusion into the lumen is noted on angiography in 2 orthogonal views.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Global Cohort 1; All subjects to be treated with the Stellarex 035 Drug Coated Balloon (DCB) for Percutaneous Transluminal Angioplasty (PTA).The drug coating is paclitaxel (PTX).	Device: Stellarex 0.035" Over-the-Wire (OTW) drug-coated angioplasty balloon (Stellarex DCB); Percutaneous Transluminal Angioplasty will be completed using a 2.0 micrograms per square millimeter. Paclitaxel-Coated Balloon. Balloon will be inflated to a size appropriate for the target vessel, as determined by the physician. Total balloon inflation time is determined by the physician, but no less than one minute.; Other Names: CVI Paclitaxel-Coated PTA Balloon Catheter
Experimental: ISR Cohort 2; All subjects to be treated with the Stellarex 035 Drug Coated Balloon (DCB) for Percutaneous Transluminal Angioplasty (PTA).The drug coating is paclitaxel (PTX).	Device: Stellarex 0.035" Over-the-Wire (OTW) drug-coated angioplasty balloon (Stellarex DCB); Percutaneous Transluminal Angioplasty will be completed using a 2.0 micrograms per square millimeter. Paclitaxel-Coated Balloon. Balloon will be inflated to a size appropriate for the target vessel, as determined by the physician. Total balloon inflation time is determined by the physician, but no less than one minute.; Other Names: CVI Paclitaxel-Coated PTA Balloon Catheter

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Freedom From Device and Procedure-related Death and Freedom From 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 (TLR) through 12 months post-procedure.	Through 12 months post-procedure.
Percentage of Lesions Free From Restenosis	Primary patency at 12 months post-procedure. Primary patency is defined as the absence of target lesion restenosis per duplex ultrasound (peak systolic velocity ratio (PSVR) ≤ 2.5) and freedom from clinically-driven target lesion revascularization.	12 months post-procedure.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Efficacy Endpoint	The secondary efficacy outcome was freedom from target lesions revascularization (TLR) at 12 months post-procedure and compared to a performance goal.	12 months post-procedure

Collaborators and Investigators

• Sponsor: Spectranetics Corporation
• Investigators: Principal Investigator: Thomas Zeller, MBChB, FRANZCR, Herz-Zentrum Bad Krozingen, Germany; Principal Investigator: Andrew Holden, MD, Auckland Hospital, New Zealand; Principal Investigator: Yann Goueffic, MD, Hopital Nord Laennec, France

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.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2013
• Primary Completion (Actual): August 1, 2020
• Study Completion (Actual): August 1, 2022

Study Registration Dates

• First Submitted: July 25, 2013
• First Submitted That Met QC Criteria: August 19, 2013
• First Posted (Estimate): August 22, 2013

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

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: CP-1005; CP-1005B (Other Identifier: Spectranetics)

Drug and device information, study documents

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