Clinical trial NCT01927068: STELLAREX: ILLUMENATE Global and In-Stent Restenosis (ISR)
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Peripheral Arterial Disease
Lead sponsor: Spectranetics Corporation
Sponsor class: INDUSTRY
First posted: 2013-08-22
Enrollment: 499
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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.

Primary outcomes:
measure: Percentage of Participants With Freedom From Device and Procedure-related Death and Freedom From Target Limb Major Amputation and Clinically-driven Target Lesion Revascularization
timeFrame: Through 12 months post-procedure.
measure: Percentage of Lesions Free From Restenosis
timeFrame: 12 months post-procedure.
Secondary outcomes:
measure: Secondary Efficacy Endpoint
timeFrame: 12 months post-procedure
Other outcomes:
Locations:
city: Auchenflower
country: Australia
facility: The Wesley St. Andrew Research Institute Ltd.
city: Bedford
country: Australia
facility: Flinders Medical Centre
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital
city: Dandenong
country: Australia
facility: Monash Medical Centre at Dandenong Campus
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
city: Graz
country: Austria
facility: Medizinische Universität Graz - Univ. Klinik für Innere Medizin
city: Aalst
country: Belgium
facility: Onze Lieve Vrouw Ziekenhuis
city: Antwerpen
country: Belgium
facility: Middelheim Hospital
city: Bonheiden
country: Belgium
facility: Imelda Hospital
city: Dendermonde
country: Belgium
facility: AZ Sint-Blasius
city: Genk
country: Belgium
facility: ZOL Campus Sint Jan
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: University Clinic Leuven
city: Tienen
country: Belgium
facility: Regionaal Ziekenhuis Heilig Hart Tienen, Campus Mariëndal - MCT, Vascular Surgery Department
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand, Hôpital Gabriel Montpied
city: Lyon
country: France
facility: CHU de Lyon, Hôpital Edouard Herriot
city: Marseille
country: France
facility: Hopital de Ia Timone
city: Nantes
country: France
facility: CHU de Nantes, Hôpital Nord Laennec
city: Paris
country: France
facility: Hôpital Européen georges Pompidou
city: Rennes
country: France
facility: CHU de Rennes, Hôpital Pontchaillou
city: Toulouse
country: France
facility: Clinique Pasteur
city: Bad Krozingen
country: Germany
facility: Universitats-Herzzentrum Freiburg - Bad Krozingen
city: Berlin
country: Germany
facility: Jüdisches Krankenhaus Berlin
city: Heidelberg
country: Germany
facility: Medizinische Universitätsklinik III
city: Immenstadt
country: Germany
facility: Klinikum Immenstadt, Herz-und Gefässzentrum Oberallgäu-Kempten
city: Langensteinbach
country: Germany
facility: SRH Klinikum Karlsbad-Langensteinbach
city: Leipzig
country: Germany
facility: University Leipzig Medical Center
city: Rosenheim
country: Germany
facility: RoMed Klinikum Rosenheim
city: Tübingen
country: Germany
facility: Universitatsklinik, Abteilung Für Diagnostische und Inverventionelle Radiologie
city: Ancona
country: Italy
facility: Ospedali Riuniti - SOD
city: Palermo
country: Italy
facility: Villa Maria Eleonora Hospital
city: Perugia
country: Italy
facility: S.C. Chirurgia Vascolare ed Endovascolare
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Auckland
country: New Zealand
facility: Middlemore Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Wellington
country: New Zealand
facility: Wellington Hospital
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Warszawa
country: Poland
facility: Instytut Hematologii i Transfuzjologii
city: Barcelona
country: Spain
facility: Centre d'Atencio Integral Hospital Dos de Maig
city: Madrid
country: Spain
facility: Hospital Universitario Quirón de Madrid
city: London
country: United Kingdom
facility: Imperial College Academic and Healthcare NHS Trust, St. Mary's Hospital
city: London
country: United Kingdom
facility: King's College
city: London
country: United Kingdom
facility: UCL Division of Surgery and Interventional Science
Study officials:
affiliation: Herz-Zentrum Bad Krozingen, Germany
name: Thomas Zeller, MBChB, FRANZCR
role: PRINCIPAL_INVESTIGATOR
affiliation: Auckland Hospital, New Zealand
name: Andrew Holden, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Nord Laennec, France
name: Yann Goueffic, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.