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

Critical Lower Limb Ischemia Clinical Trial

— INPACT-DEEP  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00941733
• Other study ID #: P998
• Status: Completed
• Phase: N/A
• First received: July 16, 2009
• Last updated: January 31, 2018
• Start date: September 2009
• Est. completion date: November 30, 2017

Study information

• Verified date: January 2018
• Source: Medtronic Endovascular
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 358
• Est. completion date: November 30, 2017
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Critical Lower Limb Ischemia
• Ischemia

Intervention

Device:
• IN.PACT Amphirion
Balloon Angioplasty
• Standard PTA
Balloon Angioplasty

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Medtronic Endovascular

Countries where clinical trial is conducted

Austria,  Belgium,  Germany,  Italy,  Netherlands,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Amputation Free Survival	Percentage of participants with a 1 year amputation free survival.	12 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Procedural Success	Percentage of patients with a procedural success defined as combination of technical success, device success and absence of procedural complications	Day 1
Secondary	Days of Hospitalization	Days of hospitalization at 1 year	12 months
Secondary	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

External 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