Study of IN.PACT Amphirion™ Drug Eluting Balloon vs. Standard PTA for the Treatment of Below the Knee Critical Limb Ischemia (INPACT-DEEP)

Randomized Study of IN.PACT Amphirion™ Drug Eluting Balloon vs. Standard PTA (Percutaneous Transluminal Angioplasty) for the Treatment of Below the Knee Critical Limb Ischemia

This is a prospective, multi-center, randomized (2:1) trial of symptomatic patients with critical limb ischemia (CLI) secondary to atherosclerotic lesions (stenotic or occluded) of the infrapopliteal vessels. Patients will undergo a percutaneous transluminal endovascular procedure with either the IN.PACT Amphirion™ drug eluting balloon or with a standard (Percutaneous Transluminal Angioplasty) PTA balloon. Patients will be followed with pre-study, post-study, and follow-up evaluations.

Study Overview

• Status: Completed
• Conditions: Critical Lower Limb Ischemia
• Intervention / Treatment: Device: IN.PACT Amphirion; Device: Standard PTA

• Study Type: Interventional
• Enrollment (Actual): 358
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria
    • Medical University Graz
• Belgium
  • Bonheiden, Belgium
    • Imelda Hospital
  • Dendermonde, Belgium
    • AZ Sint-Blasius
  • Genk, Belgium
    • ZOL St. jan
  • Gent, Belgium
    • Ghent University Hospital
• Germany
  • Bad Krozingen, Germany, 79189
    • Herz-Zentrum Bad Krozingen
  • Hamburg, Germany
    • Medical Care Center
  • Heidelberg, Germany
    • University Hospital Heidelberg
  • Leipzig, Germany, 04289
    • Park-Krankenhaus Leipzig
• Italy
  • Palermo, Italy
    • Villa Maria Eleonora Hospital
• Netherlands
  • Nieuwegein, Netherlands
    • St. Antonius Hospital
• Switzerland
  • Bern, Switzerland, 3010
    • University of Bern
  • Luzern, Switzerland
    • Luzerner Kantonsspital

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

Inclusion Criteria:

General Inclusion Criteria

• Age ≥18 years and ≤85 years
• Patient or patient's legal representative have been informed of the nature of the study, agrees to participate and has signed an Ethical Committee approved consent form
• Female patients of childbearing potential have a negative pregnancy test ≤7 days before the procedure and are willing to use a reliable method of birth control for the duration of study participation
• Patient has documented chronic Critical Limb Ischemia (CLI) in the target limb prior to the study procedure with Rutherford Category 4, 5 or 6
• Life expectancy >1 year in the Investigator's opinion

General Angiographic Inclusion Criteria

• Reference vessel(s) diameter between 2 and 4 mm
• Single or multiple lesions with ≥70% diameter stenosis (DS) of different lengths in one or more main afferent crural vessels including the tibioperoneal trunk
• At least one non occluded crural vessel with angiographically documented run-off to the foot either direct or through collaterals

Angiographic Inclusion Criteria for Late Lumen Loss (LLL) assessment

• Angio-target lesion (TL) is one identifiable single solitary or series of multiple adjacent lesions with a diameter stenosis (DS) ≥70% and a cumulative length ≤100 mm that can be covered by a single IN.PACT Amphirion™ (10 mm balloon landing zone in both edges is mandatory)
• Angio-target lesion (TL) is the only lesion in that vessel (only one Angio-TL per patient is allowed)

Exclusion Criteria:

General Exclusion Criteria

• Patient unwilling or unlikely to comply with Follow-Up schedule
• Planned major index limb amputation

General Angiographic Exclusion Criteria

• Lesion and / or occlusions located or extending in the popliteal artery or below the ankle joint space
• Inflow lesion or occlusion in the ipsilateral Iliac, Superficial Femoral Artery (SFA), popliteal arteries with length ≥15 cm
• Significant (≥50% DS) inflow lesion or occlusion in the ipsilateral Iliac, Superficial Femoral Artery (SFA) and popliteal arteries left untreated
• Previously implanted stent in the target lesions(s)
• Aneurysm in the target vessel
• Acute thrombus in the target limb

General Procedural Exclusion Criteria

• Failure to obtain a <30% residual stenosis in pre-existing, hemodynamically significant (≥50% diameter stenosis (DS) and <15 cm length) inflow lesions in the ipsilateral iliac, SFA and popliteal artery. No Drug Eluting Stents (DES) and / or Drug Eluting Balloon (DEB) allowed for the treatment of inflow lesions.
• Failure to cross the TL with a 0.014" guide wire
• Use of alternative therapy, e.g. atherectomy, cutting balloon, laser, radiation therapy, DES as part of the index procedure

ANGIOGRAPHIC cohort General Exclusion Criteria:

- Glomerular Filtration Rate (GFR) <30 ml/min except for patients with renal end stage disease on chronic haemodialysis

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug Eluting Balloon; Intervention: IN.PACT Amphirion™	Device: IN.PACT Amphirion; Balloon Angioplasty
Active Comparator: Standard PTA; Intervention: Standard PTA	Device: Standard PTA; Balloon Angioplasty

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late Lumen Loss (LLL) of the Target Lesion by Quantitative Vascular Angiography (QVA)	The difference between minimum lumen diameter (MLD) immediately after Percutaneous Transluminal Angioplasty (PTA) and MLD at 12 months follow-up	12 months or at Target Lesion Revascularization (TLR) time
Clinically Driven Target Lesion Revascularization (TLR) of the Target Lesion in the Amputation Free Surviving Patients	Percentage of participants in the amputation free survival population with Clinically driven Target Lesion Revascularization (CD-TLR) at 12 months, CD-TLR defined as any TLR of the target lesion associated with Deterioration of Rutherford Class and / or increase in size of pre-existing wounds and / or occurrence of a new wound(s).	12 months
Composite of All Cause Death, Major Amputation and Clinically Driven Target Lesion Revascularization (CD-TLR)	Percentage of participants experiencing all cause death, major amputation and clinically driven Target Lesion Revascularization (CD-TLR) at 6 months. CD-TLR defined as any TLR of the target lesion associated with Deterioration of Rutherford Class and / or increase in size of pre-existing wounds and / or occurrence of a new wound(s)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amputation Free Survival	Percentage of participants with a 1 year amputation free survival.	12 months
Rate of Wound Healing	Percentage of participants with completed wound healing, wound healing as defined as core lab adjudication of > 50% area/volume reduction of baseline ulcer(s) in the treated leg at 1 year.	12 months
Amputation Free Survival and Wound Healing	Percentage of participants with a 1 year amputation free survival and wound healing. Wound healing is defined as core lab adjudication of > 50% area/volume reduction of baseline ulcer(s) in the treated leg at a specified time point.	12 months
Amputation Free Survival and Resolved Critical Limb Ischemia (CLI)	Percentage of participants with an amputation free survival and resolved Critical Limb Ischemia (CLI) at 1 year.	12 months
Death, Amputation and Clinically Driven Target Lesion Revascularization (TLR)	Percentage of participants that experienced death, amputation and clinically driven Target Lesion Revascularization (TLR) at 1 year.	12 months
Primary Sustained Clinical Improvement	Percentage of participants that experienced primary sustained clinical improvement at 1 year, specified as an improvement shift in the Rutherford classification of one class in amputation free, clinically driven target lesion revascularization (TLR) free surviving subjects.	12 months
Secondary Sustained Clinical Improvement	Percentage of participants that experienced a secondary sustained clinical improvement, specified as an improvement shift in the Rutherford classification of one class including the need for clinically driven TLR in amputation free surviving subjects at 1 year.	12 months
Quality of Life Assessment by EQ5D	Quality of life assessment by EQ5D at 1 year compared to baseline. EQ-5D is a standardised measure of health status and economic appraisal. The EQ-5D-3L essentially consists of 2 parts:the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: (1) no problems, (2) some problems, (3) extreme problems. The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. EQ-5D health states can be converted into a single summary index where 0.0='worst possible outcome' and 1.0='best possible outcome'.	12 months
Walking Capacity Assessment	Walking Impairment assessment by WIQ at 1 year compared to baseline. The Walking Impairment Questionnaire (WIQ) is a questionnaire for evaluating walking impairment in patients with peripheral arterial disease (PAD). This can be used to identify patients with significant impairment and to monitor effectiveness of therapeutic interventions. The questionnaire was self-administered by the patients and contains three domains measuring three important factors of walking impairment in patients with intermittent claudication: (1) difficulty walking a distance during the past month, (2) difficulty walking at a certain speed during the past month, (3) symptoms associated with walking impairment. For each separate domain, a subscore was calculated. The total WIQ score was defined as the mean of the three subscores. A WIQ score of 42.5 or less identified low performers; while a score of 75.5 or more identified high performers. The WIQ score range is 0 (minimum) - 100 (maximum).	12 months
MAE (Major Adverse Events)	Percentage of participants with a MAE (Major Adverse Events) at 1 year. Major Adverse Events, defined as Death of any Cause, Major Amputation of target limb, Minor Amputation of target limb	12 months
Device Success	Percentage of device success defined as exact deployment of the device according to the instructions for use as documented with suitable imaging modalities	Day 1
Technical Success	Percentage of technical success defined as successful vascular access and completion of the endovascular procedure and immediate morphological success with less or equal to 50% residual diameter reduction of the treated lesion on completion angiography	Day 1
Procedural Success	Percentage of patients with a procedural success defined as combination of technical success, device success and absence of procedural complications	Day 1
Days of Hospitalization	Days of hospitalization at 1 year	12 months
Improvement % Diameter Stenosis (%DS) of the Target Leasion (TL) Assessed by Quantitative Vascular Angiography (QVA)	Percentage of participants with an improvement in percent diameter stenosis (%DS) of the target leasion (TL) assessed by Quantitative Vascular Angiography (QVA)	12 months

Collaborators and Investigators

• Sponsor: Medtronic Endovascular
• Investigators: Principal Investigator: Iris Baumgartner, MD, University Hospital Inselspital, Berne; Principal Investigator: Dierk Scheinert, MD, Heart Center Leipzig - University Hospital; Principal Investigator: Thomas Zeller, MD, University Heart Center Freiburg - Bad Krozingen

Publications and helpful links

General Publications

• Zeller T, Micari A, Scheinert D, Baumgartner I, Bosiers M, Vermassen FEG, Banyai M, Shishehbor MH, Wang H, Brodmann M; IN.PACT DEEP Trial Investigators. The IN.PACT DEEP Clinical Drug-Coated Balloon Trial: 5-Year Outcomes. JACC Cardiovasc Interv. 2020 Feb 24;13(4):431-443. doi: 10.1016/j.jcin.2019.10.059.
• Zeller T, Baumgartner I, Scheinert D, Brodmann M, Bosiers M, Micari A, Peeters P, Vermassen F, Landini M, Snead DB, Kent KC, Rocha-Singh KJ; IN.PACT DEEP Trial Investigators. Drug-eluting balloon versus standard balloon angioplasty for infrapopliteal arterial revascularization in critical limb ischemia: 12-month results from the IN.PACT DEEP randomized trial. J Am Coll Cardiol. 2014 Oct 14;64(15):1568-76. doi: 10.1016/j.jacc.2014.06.1198.
• Zeller T, Baumgartner I, Scheinert D, Brodmann M, Bosiers M, Micari A, Peeters P, Vermassen F, Landini M; IN.PACT DEEP Trial Investigators. IN.PACT Amphirion paclitaxel eluting balloon versus standard percutaneous transluminal angioplasty for infrapopliteal revascularization of critical limb ischemia: rationale and protocol for an ongoing randomized controlled trial. Trials. 2014 Feb 19;15:63. doi: 10.1186/1745-6215-15-63.

Helpful Links

• Zeller et al. Drug-Eluting Balloon Versus Standard Balloon Angioplasty for Infrapoplliteal Arterial Revascularization in CLI - 12-Month Results from the IN.PACT DEEP Randomized trial.Journal of the American College of Cardiology 2014; 64; 15

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): November 30, 2017

Study Registration Dates

• First Submitted: July 16, 2009
• First Submitted That Met QC Criteria: July 17, 2009
• First Posted (Estimate): July 20, 2009

Study Record Updates

• Last Update Posted (Actual): February 28, 2018
• Last Update Submitted That Met QC Criteria: January 31, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: BTK; CLI; PTA
• Additional Relevant MeSH Terms: Pathologic Processes; Ischemia
• Other Study ID Numbers: P998