Global Study of a Drug-coated Balloon to Treat Obstructive SFA and/or Popliteal Lesions (ILLUMENATE)

• ClinicalTrials.gov Identifier: NCT01927068
• Recruitment Status: Active, not recruiting
• First Posted: August 22, 2013
• Last Update Posted: August 22, 2019
• Sponsor: Spectranetics Corporation
• Information provided by (Responsible Party): Spectranetics Corporation

Study Description

Brief Summary:

Cohort 1: Single-Arm, multicenter study to continue to assess the safety and performance of 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

Condition or disease	Intervention/treatment	Phase
Peripheral Arterial Disease	Device: CVI Paclitaxel-Coated PTA Balloon Catheter	Not Applicable

Detailed Description:

Cohort 1:

The purpose of this single arm study is to continue to assess safety and performance of the CVI Paclitaxel-Coated PTA Balloon Catheter 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 patients.

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 500 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: ILLUMENATE GLOBAL and ISR: 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
• Study Start Date: July 2013
• Estimated Primary Completion Date: April 5, 2022
• Estimated Study Completion Date: July 5, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Global Cohort 1; All subjects to be treated with the CVI Paclitaxel-Coated, Percutaneous Transluminal Angioplasty (PTX PTA) Balloon Catheter in Cohort 1.	Device: CVI Paclitaxel-Coated PTA Balloon Catheter; 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 Name: Stellarex 0.035" Over-the-Wire (OTW) drug-coated angioplasty balloon (Stellarex DCB)
Experimental: Global ISR Cohort 2; For Cohort 2, the same device was commercially available, and subjects were to be treated with the CE Marked, renamed device Stellarex 0.035" OTW drug-coated angioplasty balloon (Stellarex 035 DCB)	Device: CVI Paclitaxel-Coated PTA Balloon Catheter; 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 Name: Stellarex 0.035" Over-the-Wire (OTW) drug-coated angioplasty balloon (Stellarex DCB)

Outcome Measures

Primary Outcome Measures :

1. Primary Safety Endpoint [ Time Frame: Through 30 days post-procedure. ]
   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.
2. Primary Efficacy Endpoint [ Time Frame: 12 months post-procedure. ]
   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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

  Show 44 Study Locations

Sponsors and Collaborators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Spectranetics Corporation
• ClinicalTrials.gov Identifier: NCT01927068 History of Changes
• Other Study ID Numbers: CP-1005; CP-1005 ( Other Identifier: Spectranetics )
• First Posted: August 22, 2013
• Last Update Posted: August 22, 2019
• Last Verified: August 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: No
• Pediatric Postmarket Surveillance of a Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Peripheral Arterial Disease; Peripheral Vascular Diseases; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Paclitaxel; Albumin-Bound Paclitaxel; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action