BIO REsponse Adapted Combination Therapy Pilot Study

Peripheral Arterial Disease Clinical Trial

Official title:

Evaluation of Adjunctive Procedural Assessments to Diagnose Post Drug-coated Balloon Flow-limiting Dissection and Residual Stenosis When Angiography is Inconclusive

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03547986
• Other study ID #: C1706
• Status: Active, not recruiting
• Phase: N/A
• Start date: November 9, 2018
• Est. completion date: March 2024

Study information

• Verified date: August 2022
• Source: Biotronik AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Both drug-coated balloon and stents have been used for a number of years to treat subjects with Peripheral Artery Disease (PAD) and are recognized as very good treatment methods. However, due to a higher risk of blood clot formation, requiring a longer anticoagulant treatment, and the challenge of treating re growth of tissue extending through the metal mesh of the stent, the physicians try to reserve stent placement to situation where it's really needed, in case of flow-limiting vessel dissection or acute re-narrowing.

The purpose of this study is to evaluate the utility of several procedural diagnostic techniques in helping the physicians to better decide whether a stent is needed or not.

The study will also estimate the safety and efficacy of Passeo-18 Lux drug-coated balloon associated to Pulsar 18 bare metal stent when and where needed to treat PAD

Description:

The REACT treatment concept aims at minimizing the metal burden, combining Passeo-18 Lux Drug-Coated Balloon (DCB) with Pulsar-18 thin struts bare metal stent, as low as reasonably achievable (ALARA), while benefiting from the antirestenotic properties of Paclitaxel. However, in order to optimally apply this selective stenting approach, it is needed to clearly identify when a stent is indicated. Angiographic images, even with additional projections, are sometimes insufficient to clearly determine if a dissection is flow-limiting and the subsequent stent requirement. There is currently no definition nor validated method to define flow-limiting dissection in the peripheral arteries. Even though it has been widely used, the classification developed by the National Heart, Lung, and Blood Institute to grade coronary artery dissection as A to F19, based on angiographic appearance cannot be extrapolated to peripheral arteries.

Therefore, the purpose of the study is to evaluate the incremental value of several adjunctive procedural assessments to standard angiography to identify flow-limiting dissection and residual stenosis, and better inform the operator on the stent requirement. In addition, the study will evaluate the safety and efficacy of the REACT algorithm.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 150
• Est. completion date: March 2024
• Est. primary completion date: January 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subject has provided written informed consent before any study specific test or procedure and is willing and able to comply with the required follow-up visits and procedures

• Subject has a chronic, symptomatic lower limb ischemia defined as Rutherford categories 2 to 4

Angiographic criteria:

• Single lesion or consecutive single lesions with a healthy segment(s) of = 2cm in-between

• De novo, restenotic or (re)occluded lesion(s) post Percutaneous Transluminal Angioplasty in the native superficial femoral artery (SFA) and or the proximal popliteal artery (PPA)

• Lesion(s) must be located at least 1 cm distal to the profunda femoris artery and at least 3 cm above the knee joint (radiographic joint space)

• Degree of stenosis =70% by visual angiographic assessment

• Vessel diameter = 4 and = 7 mm

• Patent inflow artery, free from significant lesion (>50%) as confirmed by angiography. Treatment of the target lesion is acceptable after successful treatment of inflow iliac and/or common femoral artery lesion. The inflow lesion cannot be treated with a DCB or a Drug Eluting Stent

• Patent infrapopliteal and popliteal artery, i.e., single vessel runoff or better with at least one of the three vessels patent (<50% stenosis) to the ankle or foot with no planned intervention

Exclusion Criteria:

• Previously stented target lesion

• Target lesion/ previously treated with drug-coated balloon <12 months prior to enrollment.

• Use of atherectomy, laser or other debulking devices in the target SFA/PPA vessel during the index procedure.

• Failure to cross the target lesion with the guide wire

• Presence of a complication following pre-dilation of target lesion, which in the opinion of the investigator would not allow the procedure to be performed in accordance with the REACT approach

• Presence of aneurysm in the target vessel.

• Prior on planned major amputation (above the ankle) in the target limb

• Acute ischemia and/or acute thrombosis of the target SFA/PPA vessel prior to enrollment.

• Perforation of the target vessel as evidenced by extravasation of contrast media prior to enrollment

• Known hypersensitivity or contraindication to contrast media that, in the opinion of the investigator, cannot be adequately pre-medicated

• Known hypersensitivity/allergy to Paclitaxel or other components of the investigational devices and comparator (e.g., nitinol, amorphous silicon carbide, polymer)

• Known hypersensitivity or contraindication to antiplatelet, anticoagulant, thrombolytic medications that would be administered during the study

• Subject with uncorrected bleeding disorders

• Subject with renal failure

• Life expectancy less than 12 months due to other comorbidities, that in the investigators opinion, could limit subject ability to comply with the study required follow-up visits/procedure and threaten the study scientific integrity

• Pregnant, breast feeding, or plan to become pregnant in the next 12 months.

• Current participation in another investigational drug or device clinical study that has not completed the primary endpoint at the time of enrollment or that upon investigator judgment could clinically interferes with the current study endpoints

Related Conditions & MeSH terms

• Peripheral Arterial Disease
• Peripheral Vascular Diseases

Intervention

Diagnostic Test:
• Duplex Ultrasound (DUS)
Occurrence of a flow-limiting dissection or residual stenosis will be assessed by standard angiography and Duplex Ultrasound
• IVUS with Intraarterial pressure measurement (IAP) if needed
Occurrence of a flow-limiting dissection or residual stenosis will be assessed by standard angiography and Intra-vascular ultrasound associated to Intraarterial pressure measurement if needed

Locations

Country	Name	City	State
Australia	Royal Perth Hospital	Perth	Western Australia
Austria	Medical University Graz	Graz
Austria	Medizinische Universität Wien	Vienna
Belgium	OLV Ziekenhuis	Aalst
Belgium	A.Z. Sint-Blasius	Dendermonde
Belgium	AZ Groeninge	Kortrijk
France	CHU de Nantes	Nantes
France	Hopital Paris Saint Joseph	Paris
Germany	Karolinen-Hospital, Klinikum Arnsberg	Arnsberg
Germany	Universitäts-Herzzentrum Freiburg • Bad Krozingen	Bad Krozingen
Germany	SRH Klinikum Karlsbad-Langensteinbach	Biederbach Baden-Wurttemberg
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Universitätsklinikum	Tübingen
Germany	GRN Hospital	Weinheim
Spain	Hospital General de Guadalajara	Guadalajara

Sponsors (1)

Lead Sponsor	Collaborator
Biotronik AG

Countries where clinical trial is conducted

Australia,  Austria,  Belgium,  France,  Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	diagnostic accuracy of duplex ultrasound	specificity and sensitivity of duplex ultrasound combined to angiography vs angiography alone	during index procedure
Secondary	diagnostic accuracy of intraarterial pressure measurement	specificity and sensitivity of intraarterial pressure measurement combined to angiography vs angiography alone	during index procedure
Secondary	diagnostic accuracy of intraarterial pressure measurement with IVUS	specificity and sensitivity of intraarterial pressure measurement with IVUS combined to angiography vs angiography alone	during index procedure
Secondary	Target lesion stenting rate		during index procedure
Secondary	Number of stents used per target lesion		during index procedure
Secondary	Average stent length per target lesion		during index procedure
Secondary	Average target lesion length stented (full, spot)		during index procedure
Secondary	DCB technical success	Delivery and successful use of Passeo-18 Lux DCB to the target lesion to achieve a residual stenosis no greater than 30% in the absence of flow-limiting dissection	during index procedure
Secondary	Stent technical success	delivery and successful use of Pulsar-18 to the target lesion to achieve a residual stenosis no greater than 30%	during index procedure
Secondary	Procedural success	technical success and no MAEs before discharge	during index procedure
Secondary	Primary Patency	Primary patency is defined as DUS peak systolic velocity ratio (PSVR) =2.5 at the target lesion, in the absence of clinically driven Target Lesion Revascularization (cd TLR).	1, 6 and 12 months post index procedure
Secondary	Major Adverse Event (MAE)	Major adverse event (MAE) is defined as device or procedure related death within 30 days post index procedure, major target limb amputation or cd TLR post index procedure	1, 6 and 12 months post index procedure
Secondary	Major Adverse Cardiac Event (MACE)	Major adverse Cardiac event (MACE) is defined as death all causes, myocardial infarction, stroke, death or major amputation	1, 6 and 12 months post index procedure
Secondary	Major Adverse Limb Event (MALE)	Major adverse limb event (MALE) is defined as severe limb ischemia leading to an intervention or major vascular amputation	1, 6 and 12 months post index procedure
Secondary	Clinically driven Target Lesion Revascularization	Clinical Event Committee adjudicated TLR =Any post index procedure surgical or percutaneous intervention to the target lesion plus 5 mm proximal and distal to the stented lesion edge when a stent is used	1, 6, 12, 24 and 36 months post index procedure
Secondary	Major target limb amputation rate		1, 6, 12, 24 and 36 months post index procedure
Secondary	all cause of death rate		1, 6, 12, 24 and 36 months post index procedure
Secondary	Hemodynamic improvement	change in Ankel Brachial Index at 1, 6 and 12 months post index procedure compared to baseline	1, 6 and 12 months post index procedure
Secondary	Rate of primary sustained clinical improvement	Improvement in Rutherford Classification of at least one category for claudicants and by wound-healing and resting pain resolution for critical limb ischemia as compared to pre-procedure without the need for repeat TLR	1, 6 and 12 months post index procedure
Secondary	Rate of secondary sustained clinical improvement	Improvement in Rutherford Classification of at least one category for claudicants and by wound-healing and resting pain resolution for critical limb ischemia as compared to pre-procedure including the need for repeat TLR	1, 6 and 12 months post index procedure
Secondary	Health Related Quality of Life	The Euroquol Group 5 dimension quality of life questionnaire (EQ-5D) is a descriptive system comprising 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The results in a 1-digit number expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes patient's health state.; The EQ Visual Analogue Scale records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement	baseline, 1, 6 and 12 months post index procedure
Secondary	Walk Impairment	The Walk Impairment Questionnaire (WIQ) measure measures self-reported walking distance, walking speed, and stair-climbing ability	baseline, 1, 6 and 12 months post index procedure
Secondary	Resource utilisation	Costs will be evaluated using specific information on resource use	during index procedure, 12 month