BIO REsponse Adapted Combination Therapy Pilot Study

• ClinicalTrials.gov Identifier: NCT03547986
• Recruitment Status: Active, not recruiting
• First Posted: June 6, 2018
• Last Update Posted: August 17, 2020
• Sponsor: Biotronik AG
• Information provided by (Responsible Party): Biotronik AG

Study Description

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

Condition or disease	Intervention/treatment	Phase
Peripheral Arterial Disease	Diagnostic Test: Duplex Ultrasound (DUS); Diagnostic Test: IVUS with Intraarterial pressure measurement (IAP) if needed	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 150 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: The existing and new diagnostic method are performed on the same patients (paired data)
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Evaluation of Adjunctive Procedural Assessments to Diagnose Post Drug-coated Balloon Flow-limiting Dissection and Residual Stenosis When Angiography is Inconclusive
• Actual Study Start Date: November 9, 2018
• Estimated Primary Completion Date: December 2020
• Estimated Study Completion Date: December 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Duplex Ultrasound (DUS); Standard angiography and DUS are performed on the same patients (paired data)	Diagnostic Test: Duplex Ultrasound (DUS); Occurrence of a flow-limiting dissection or residual stenosis will be assessed by standard angiography and Duplex Ultrasound; Other Name: Procedural diagnostic with Duplex Ultrasound (DUS)
Experimental: IVUS with Intraarterial pressure measurement (IAP); Standard angiography and Intra-Vascular Ultrasound (IVUS) with Intraarterial pressure measurement (IAP) are performed on the same patients (paired data)	Diagnostic Test: 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; Other Name: Procedural diagnostic with IVUS and Intraarterial pressure measurement (IAP)

Outcome Measures

Primary Outcome Measures :

1. diagnostic accuracy of duplex ultrasound [ Time Frame: during index procedure ]
   specificity and sensitivity of duplex ultrasound combined to angiography vs angiography alone

Secondary Outcome Measures :

1. diagnostic accuracy of intraarterial pressure measurement [ Time Frame: during index procedure ]
   specificity and sensitivity of intraarterial pressure measurement combined to angiography vs angiography alone
2. diagnostic accuracy of intraarterial pressure measurement with IVUS [ Time Frame: during index procedure ]
   specificity and sensitivity of intraarterial pressure measurement with IVUS combined to angiography vs angiography alone
3. Target lesion stenting rate [ Time Frame: during index procedure ]
4. Number of stents used per target lesion [ Time Frame: during index procedure ]
5. Average stent length per target lesion [ Time Frame: during index procedure ]
6. Average target lesion length stented (full, spot) [ Time Frame: during index procedure ]
7. DCB technical success [ Time Frame: during index procedure ]
   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
8. Stent technical success [ Time Frame: during index procedure ]
   delivery and successful use of Pulsar-18 to the target lesion to achieve a residual stenosis no greater than 30%
9. Procedural success [ Time Frame: during index procedure ]
   technical success and no MAEs before discharge
10. Primary Patency [ Time Frame: 1, 6 and 12 months post index procedure ]
    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).
11. Major Adverse Event (MAE) [ Time Frame: 1, 6 and 12 months post index procedure ]
    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
12. Major Adverse Cardiac Event (MACE) [ Time Frame: 1, 6 and 12 months post index procedure ]
    Major adverse Cardiac event (MACE) is defined as death all causes, myocardial infarction, stroke, death or major amputation
13. Major Adverse Limb Event (MALE) [ Time Frame: 1, 6 and 12 months post index procedure ]
    Major adverse limb event (MALE) is defined as severe limb ischemia leading to an intervention or major vascular amputation
14. Clinically driven Target Lesion Revascularization [ Time Frame: 1, 6 and 12 months post index procedure ]
    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
15. Major target limb amputation rate [ Time Frame: 1, 6 and 12 months post index procedure ]
16. all cause of death rate [ Time Frame: 1, 6 and 12 months post index procedure ]
17. Hemodynamic improvement [ Time Frame: 1, 6 and 12 months post index procedure ]
    change in Ankel Brachial Index at 1, 6 and 12 months post index procedure compared to baseline
18. Rate of primary sustained clinical improvement [ Time Frame: 1, 6 and 12 months post index procedure ]
    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
19. Rate of secondary sustained clinical improvement [ Time Frame: 1, 6 and 12 months post index procedure ]
    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
20. Health Related Quality of Life [ Time Frame: baseline, 1, 6 and 12 months post index procedure ]

    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

21. Walk Impairment [ Time Frame: baseline, 1, 6 and 12 months post index procedure ]
    The Walk Impairment Questionnaire (WIQ) measure measures self-reported walking distance, walking speed, and stair-climbing ability
22. Resource utilisation [ Time Frame: during index procedure, 12 month ]
    Costs will be evaluated using specific information on resource use

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Australia, Western Australia

Royal Perth Hospital

Perth, Western Australia, Australia, 6000

Austria

Medical University Graz

Graz, Austria

Medizinische Universität Wien

Vienna, Austria

Belgium

OLV Ziekenhuis

Aalst, Belgium

A.Z. Sint-Blasius

Dendermonde, Belgium

AZ Groeninge

Kortrijk, Belgium

France

CHU de Nantes

Nantes, France

Hopital Paris Saint Joseph

Paris, France

Germany

Karolinen-Hospital, Klinikum Arnsberg

Arnsberg, Germany

Universitäts-Herzzentrum Freiburg • Bad Krozingen

Bad Krozingen, Germany, 79189

SRH Klinikum Karlsbad-Langensteinbach

Karlsbad, Germany

Universitätsklinikum Leipzig

Leipzig, Germany

Universitätsklinikum

Tübingen, Germany

GRN Hospital

Weinheim, Germany

Spain

Hospital General de Guadalajara

Guadalajara, Spain

Sponsors and Collaborators

Biotronik AG

Investigators

• Principal Investigator: Koen Deloose, MD; Sint Blasius Hospital Dendermonde, Belgium
• Principal Investigator: Patrice Bibombe Mwipatayi, MD; Royal Perth Hospital
• Principal Investigator: Michael Lichtenberg, MD; Clinic Arnsberg

More Information

• Responsible Party: Biotronik AG
• ClinicalTrials.gov Identifier: NCT03547986
• Other Study ID Numbers: C1706
• First Posted: June 6, 2018
• Last Update Posted: August 17, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Biotronik AG:

flow-limiting dissection; residual stenosis

Additional relevant MeSH terms:

Peripheral Arterial Disease; Peripheral Vascular Diseases; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases