Clinical trial NCT03547986: BIO REsponse Adapted Combination Therapy Pilot Study
Official title: Evaluation of Adjunctive Procedural Assessments to Diagnose Post Drug-coated Balloon Flow-limiting Dissection and Residual Stenosis When Angiography is Inconclusive
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Peripheral Arterial Disease
Keywords: flow-limiting dissection
residual stenosis
Lead sponsor: Biotronik AG
Sponsor class: INDUSTRY
First posted: 2018-06-06
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The existing and new diagnostic method are performed on the same patients (paired data)
Primary purpose: DIAGNOSTIC

Brief 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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: diagnostic accuracy of duplex ultrasound
timeFrame: during index procedure
Secondary outcomes:
measure: diagnostic accuracy of intraarterial pressure measurement
timeFrame: during index procedure
measure: diagnostic accuracy of intraarterial pressure measurement with IVUS
timeFrame: during index procedure
measure: Target lesion stenting rate
timeFrame: during index procedure
measure: Number of stents used per target lesion
timeFrame: during index procedure
measure: Average stent length per target lesion
timeFrame: during index procedure
measure: Average target lesion length stented (full, spot)
timeFrame: during index procedure
measure: DCB technical success
timeFrame: during index procedure
measure: Stent technical success
timeFrame: during index procedure
measure: Procedural success
timeFrame: during index procedure
measure: Primary Patency
timeFrame: 1, 6 and 12 months post index procedure
measure: Major Adverse Event (MAE)
timeFrame: 1, 6 and 12 months post index procedure
measure: Major Adverse Cardiac Event (MACE)
timeFrame: 1, 6 and 12 months post index procedure
measure: Major Adverse Limb Event (MALE)
timeFrame: 1, 6 and 12 months post index procedure
measure: Clinically driven Target Lesion Revascularization
timeFrame: 1, 6, 12, 24 and 36 months post index procedure
measure: Major target limb amputation rate
timeFrame: 1, 6, 12, 24 and 36 months post index procedure
measure: all cause of death rate
timeFrame: 1, 6, 12, 24 and 36 months post index procedure
measure: Hemodynamic improvement
timeFrame: 1, 6 and 12 months post index procedure
measure: Rate of primary sustained clinical improvement
timeFrame: 1, 6 and 12 months post index procedure
measure: Rate of secondary sustained clinical improvement
timeFrame: 1, 6 and 12 months post index procedure
measure: Health Related Quality of Life
timeFrame: baseline, 1, 6 and 12 months post index procedure
measure: Walk Impairment
timeFrame: baseline, 1, 6 and 12 months post index procedure
measure: Resource utilisation
timeFrame: during index procedure, 12 month
Other outcomes:
Locations:
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Graz
country: Austria
facility: Medical University Graz
city: Vienna
country: Austria
facility: Medizinische Universität Wien
city: Aalst
country: Belgium
facility: OLV Ziekenhuis
city: Dendermonde
country: Belgium
facility: A.Z. Sint-Blasius
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: Hopital Paris Saint Joseph
city: Arnsberg
country: Germany
facility: Karolinen-Hospital, Klinikum Arnsberg
city: Bad Krozingen
country: Germany
facility: Universitäts-Herzzentrum Freiburg • Bad Krozingen
city: Biederbach Baden-Wurttemberg
country: Germany
facility: SRH Klinikum Karlsbad-Langensteinbach
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Tübingen
country: Germany
facility: Universitätsklinikum
city: Weinheim
country: Germany
facility: GRN Hospital
city: Guadalajara
country: Spain
facility: Hospital General de Guadalajara
Study officials:
affiliation: Sint Blasius Hospital Dendermonde, Belgium
name: Koen Deloose, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Perth Hospital
name: Patrice Bibombe Mwipatayi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinic Arnsberg
name: Michael Lichtenberg, MD
role: PRINCIPAL_INVESTIGATOR
References: