<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02211664</url>
  </required_header>
  <id_info>
    <org_study_id>FMRP-120130</org_study_id>
    <nct_id>NCT02211664</nct_id>
  </id_info>
  <brief_title>Physician-Initiated Trial Investigating the Efficacy of Endovascular Treatment of Femoropopliteal Arterial Stenotic Disease With the Biotronik Passeo-18 Lux Drug Releasing Balloon and the Biotronik Pulsar-18 Stent (Comparing With 4EVER Trial Results)</brief_title>
  <acronym>BIOLUX 4EVER</acronym>
  <sponsors>
    <lead_sponsor>
      <agency>Flanders Medical Research Program</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Flanders Medical Research Program</source>
  <brief_summary>
    <textblock>
      The objective of this clinical investigation is to evaluate the short- and long-term (up to&#xD;
      24 months) outcome of treatment by means of dilation with the Passeo-18 Lux drug releasing&#xD;
      balloon and by Pulsar-18 stent implantation in symptomatic (Rutherford 2-4) femoro-popliteal&#xD;
      arterial stenotic or occlusive lesions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Ever since its introduction, one of the major limitations of endovascular therapy is the&#xD;
      occurrence of restenosis after treatment. Factors contributing to loss of primary patency&#xD;
      after percutaneous transluminal angioplasty (PTA) due to balloon injury are negative arterial&#xD;
      remodeling, excessive neointimal proliferation and elastic recoil. In order to increase&#xD;
      sustained vessel patency, systemic medication administration and brachytherapy have been&#xD;
      proposed, but have not led to any success. With the introduction of stents, patency rates&#xD;
      have been optimized also on longer term. However, neointimal hyperplasia after endovascular&#xD;
      stent placement in infra-inguinal arteries remains a major limiting issue. Stents themselves&#xD;
      contribute to this excessive intimal formation because of the vascular response to the&#xD;
      metallic prosthesis. In order to find a solution to overcome this limitation, the&#xD;
      possibilities of drug-eluting technologies are being examined.&#xD;
&#xD;
      Current concepts include drug-eluting stents (DES), which provide sustained release of&#xD;
      anti-proliferative medication into the vessel wall. The application of a drug coating on a&#xD;
      stent surface inhibits the inflammatory response and smooth muscle cell proliferation in the&#xD;
      vessel wall during a certain period and delays the process of intimal hyperplasia. Thus, DES&#xD;
      technology was developed to prevent early restenosis and late luminal loss to potentially&#xD;
      improve long-term patency rates. Because DES with active stent coatings have shown to be&#xD;
      beneficial in the treatment of coronary artery disease, the technique of active stent&#xD;
      coatings (sirolimus or paclitaxel) as commonly used in coronary interventions was transferred&#xD;
      to the infrainguinal vascular bed. However, an active stent coating (sirolimus or paclitaxel)&#xD;
      only inhibits the inflammatory response and smooth muscle cell proliferation in the vessel&#xD;
      wall for a certain period; in fact, it merely delays the process of intimal hyperplasia as&#xD;
      demonstrated by the 2-year results of the SIROCCO study.&#xD;
&#xD;
      Another novel way of inhibiting restenosis after PTA is the use of drug-coated balloons&#xD;
      (DCB), which inhibit restenosis by an immediate local release of medication during the&#xD;
      intervention. The rationale behind the use of DCBs is based on the finding that sustained&#xD;
      drug elution is not a necessary to obtain a sustained inhibition of restenosis. The concept&#xD;
      of using a balloon with medication to treat vascular disease was introduced in 2003 by&#xD;
      Scheller et al.&#xD;
&#xD;
      One of the most commonly used drugs for arterial applications is the anti-proliferative&#xD;
      paclitaxel (Taxol), which impedes cell division in the cell cycle. Paclitaxel has certain&#xD;
      characteristics which make it a promising candidate for treatment of peripheral arterial&#xD;
      disease. Because it is hydrophobic, paclitaxel does not require the use of a polymer to&#xD;
      prevent wash-off during tracking or implantation. Adequate drug delivery to the vessel wall&#xD;
      is possible because of its lipophilic characteristic, which enables paclitaxel to interact&#xD;
      with the high concentrations of lipids present in the vessel wall and avoids the need for a&#xD;
      polymer. Results of preclinical and clinical studies have shown that short-term exposure to&#xD;
      Paclitaxel may suffice to obtain a sustained reduction in late lumen loss and avoid&#xD;
      restenosis in both coronary and peripheral arteries: in contrast to stents, DCBs do not leave&#xD;
      any residual material in the artery lumen that could trigger neointimal proliferation, thus&#xD;
      making DCBs an attractive alternative to stents, especially in challenging arterial&#xD;
      anatomies. Further investigation is warranted in order to obtain conclusive data.&#xD;
      Furthermore, the benefit of treating in-stent restenosis (ISR) in the peripheral arteries&#xD;
      with DCBs has yet to be investigated, although limited data is already available to date.&#xD;
&#xD;
      The clinical value of these drug-eluting technologies has been proven repeatedly in the&#xD;
      coronary arteries, and evidence of therapeutic applications to peripheral artery disease is&#xD;
      starting to build. It is the intent of this prospective study to evaluate the treatment of a&#xD;
      drug-coated balloon followed by stent implant and comparing this to the results of the 4EVER&#xD;
      trial and results in the literature.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 2014</start_date>
  <completion_date type="Actual">March 2018</completion_date>
  <primary_completion_date type="Actual">February 2017</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Primary patency at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Defined as freedom from &gt;50% restenosis as indicated by an independently verified duplex ultrasound peak systolic velocity ratio (PSVR) &lt;2.5 in the target vessel with no reintervention.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Technical success</measure>
    <time_frame>1 day post-op</time_frame>
    <description>Defined as the ability to cross and stent the lesion to achieve residual angiographic stenosis no greater than 30% and residual stenosis less than 50% by duplex imaging.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Procedural success</measure>
    <time_frame>1 day post-op</time_frame>
    <description>Defined as the ability to perform the procedure as stated in the protocol, with the Biotronik portfolio.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of puncture site complications</measure>
    <time_frame>1 day post-op</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compression time</measure>
    <time_frame>1 day post-op</time_frame>
    <description>In patients when manual compression is applied to close the puncture site (instead of a closure device).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Primary patency rate at 1-month follow-up</measure>
    <time_frame>1 month</time_frame>
    <description>Defined as freedom from &gt;50% restenosis as indicated by an independently verified duplex ultrasound peak systolic velocity ratio (PSVR) &lt;2.5 in the target vessel with no re-intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Primary patency rate at 6- and 24-month follow-up</measure>
    <time_frame>6 and 24 months</time_frame>
    <description>Defined as freedom from &gt;50% restenosis as indicated on a duplex ultrasound with peak systolic velocity ratio (PSVR) &lt;2.5 in the target vessel with no re-intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Freedom from Target Lesion Revascularization (TLR) at at 1-, 6-, 12- and 24-months follow-up</measure>
    <time_frame>1, 6, 12 and 24 months</time_frame>
    <description>Defined as a repeat intervention to maintain or re-establish patency within the region of the treated arterial vessel plus 5mm proximal an distal to the treated lesion edge.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical success at 1-, 6-, 12- and 24-months follow-up</measure>
    <time_frame>1, 6, 12, 24 months</time_frame>
    <description>Defined as an improvement of Rutherford classification at 1-, 6-, 12- and 24-month follow-up of one class or more as compared to the pre-procedure Rutherford classification.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in ABI measurements at 1-, 6-, 12- and 24-months</measure>
    <time_frame>1, 6, 12, 24 months</time_frame>
    <description>Defined as the ankle-brachial index (ABI) measurement difference at 1-, 6-, 12- and 24-months compared to the pre-procedure ABI measurement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serious Adverse Events</measure>
    <time_frame>up to 24 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Peripheral Vascular Disease</condition>
  <arm_group>
    <arm_group_label>Passeo-18-Lux &amp; Pulsar-18</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The interventional procedure sequence consists of the following steps:&#xD;
pre-dilation of the lesion with a Passeo-18 balloon (mandatory)&#xD;
dilation of the lesion with a Passeo-18 Lux drug releasing balloon (mandatory); a maximum of 2 Passeo-18 Lux balloons can be used per lesion (drug load cannot exceed 12µg)&#xD;
stenting of the lesion with a Pulsar-18 stent (mandatory)&#xD;
post-dilation of the lesion with a Passeo-18 balloon (not mandatory)</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Passeo-18 balloon</intervention_name>
    <arm_group_label>Passeo-18-Lux &amp; Pulsar-18</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Passeo-18 Lux drug releasing balloon</intervention_name>
    <arm_group_label>Passeo-18-Lux &amp; Pulsar-18</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Pulsar-18 stent</intervention_name>
    <arm_group_label>Passeo-18-Lux &amp; Pulsar-18</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. General Inclusion Criteria:&#xD;
&#xD;
               -  De novo lesions located in the femoropopliteal arteries suitable for endovascular&#xD;
                  treatment&#xD;
&#xD;
               -  Patient presenting with a score from 2 to 4 according to the Rutherford&#xD;
                  classification&#xD;
&#xD;
               -  Patient is willing to comply with specified follow-up evaluations at the&#xD;
                  predefined time intervals time&#xD;
&#xD;
               -  Patients is &gt;18 years old&#xD;
&#xD;
               -  Patient understands the nature of the procedure and provides written informed&#xD;
                  consent, prior to enrollment in the study&#xD;
&#xD;
               -  Prior to enrollment, the target lesion was crossed with standard guidewire&#xD;
                  manipulation&#xD;
&#xD;
          2. Angiographic Inclusion Criteria:&#xD;
&#xD;
               -  The target lesions are located within the native SFA: distal point 3 cm above&#xD;
                  knee joint and 1 cm below the origin of the profunda femoralis&#xD;
&#xD;
               -  The target lesion has angiographic evidence of stenosis &gt;50% or occlusion&#xD;
&#xD;
               -  Length of the target lesion is ≤ 19 cm by visual estimation and can be covered&#xD;
                  with one stent&#xD;
&#xD;
               -  Target vessel diameter visually estimated is ≥4 mm and ≤6 mm&#xD;
&#xD;
               -  There is angiographic evidence of at least one-vessel-runoff to the foot&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of another stent in the target vessel that was placed during a previous&#xD;
             procedure&#xD;
&#xD;
          -  Presence of an aortic thrombosis or significant common femoral ipsilateral stenosis&#xD;
&#xD;
          -  Previous bypass surgery in the same limb&#xD;
&#xD;
          -  Patients contraindicated for antiplatelet therapy, anticoagulants or thrombolytics&#xD;
&#xD;
          -  Patients who exhibit persistent acute intraluminal thrombus at the target lesion site&#xD;
&#xD;
          -  Perforation at the angioplasty site evidenced by extravasation of contrast medium&#xD;
&#xD;
          -  Patients with known hypersensitivity to nickel-titanium&#xD;
&#xD;
          -  Patients with uncorrected bleeding disorders&#xD;
&#xD;
          -  Female patient with child bearing potential not taking adequate contraceptives or&#xD;
             currently breastfeeding&#xD;
&#xD;
          -  Life expectancy of less than 12 months&#xD;
&#xD;
          -  Ipsilateral iliac artery treatment before target lesion treatment with a residual&#xD;
             stenosis &gt; 30%&#xD;
&#xD;
          -  Use of thrombectomy, atherectomy or laser devices during procedure&#xD;
&#xD;
          -  Any planned surgical intervention/procedure 30 days after the study procedure&#xD;
&#xD;
          -  Any patient considered to be hemodynamically unstable at onset of procedure&#xD;
&#xD;
          -  Patient is currently participating in another investigational drug or device study&#xD;
             that has not reached the primary endpoint&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University Hospital Antwerp</name>
      <address>
        <city>Edegem</city>
        <state>Antwerp</state>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OLV Hospital</name>
      <address>
        <city>Aalst</city>
        <zip>9300</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imelda Hospital</name>
      <address>
        <city>Bonheiden</city>
        <zip>2820</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Sint-Blasius</name>
      <address>
        <city>Dendermonde</city>
        <zip>9200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>RZ Heilig Hart Hospital</name>
      <address>
        <city>Tienen</city>
        <zip>3300</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>August 6, 2014</study_first_submitted>
  <study_first_submitted_qc>August 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 7, 2014</study_first_posted>
  <last_update_submitted>August 10, 2018</last_update_submitted>
  <last_update_submitted_qc>August 10, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 13, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vascular Diseases</mesh_term>
    <mesh_term>Peripheral Vascular Diseases</mesh_term>
    <mesh_term>Peripheral Arterial Disease</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02211664
org study id: FMRP-120130
nct id: NCT02211664
lead sponsor: 
The objective of this clinical investigation is to evaluate the short- and long-term (up to
      24 months) outcome of treatment by means of dilation with the Passeo-18 Lux drug releasing
      balloon and by Pulsar-18 stent implantation in symptomatic (Rutherford 2-4) femoro-popliteal
      arterial stenotic or occlusive lesions.
Ever since its introduction, one of the major limitations of endovascular therapy is the
      occurrence of restenosis after treatment. Factors contributing to loss of primary patency
      after percutaneous transluminal angioplasty (PTA) due to balloon injury are negative arterial
      remodeling, excessive neointimal proliferation and elastic recoil. In order to increase
      sustained vessel patency, systemic medication administration and brachytherapy have been
      proposed, but have not led to any success. With the introduction of stents, patency rates
      have been optimized also on longer term. However, neointimal hyperplasia after endovascular
      stent placement in infra-inguinal arteries remains a major limiting issue. Stents themselves
      contribute to this excessive intimal formation because of the vascular response to the
      metallic prosthesis. In order to find a solution to overcome this limitation, the
      possibilities of drug-eluting technologies are being examined.

      Current concepts include drug-eluting stents (DES), which provide sustained release of
      anti-proliferative medication into the vessel wall. The application of a drug coating on a
      stent surface inhibits the inflammatory response and smooth muscle cell proliferation in the
      vessel wall during a certain period and delays the process of intimal hyperplasia. Thus, DES
      technology was developed to prevent early restenosis and late luminal loss to potentially
      improve long-term patency rates. Because DES with active stent coatings have shown to be
      beneficial in the treatment of coronary artery disease, the technique of active stent
      coatings (sirolimus or paclitaxel) as commonly used in coronary interventions was transferred
      to the infrainguinal vascular bed. However, an active stent coating (sirolimus or paclitaxel)
      only inhibits the inflammatory response and smooth muscle cell proliferation in the vessel
      wall for a certain period; in fact, it merely delays the process of intimal hyperplasia as
      demonstrated by the 2-year results of the SIROCCO study.

      Another novel way of inhibiting restenosis after PTA is the use of drug-coated balloons
      (DCB), which inhibit restenosis by an immediate local release of medication during the
      intervention. The rationale behind the use of DCBs is based on the finding that sustained
      drug elution is not a necessary to obtain a sustained inhibition of restenosis. The concept
      of using a balloon with medication to treat vascular disease was introduced in 2003 by
      Scheller et al.

      One of the most commonly used drugs for arterial applications is the anti-proliferative
      paclitaxel (Taxol), which impedes cell division in the cell cycle. Paclitaxel has certain
      characteristics which make it a promising candidate for treatment of peripheral arterial
      disease. Because it is hydrophobic, paclitaxel does not require the use of a polymer to
      prevent wash-off during tracking or implantation. Adequate drug delivery to the vessel wall
      is possible because of its lipophilic characteristic, which enables paclitaxel to interact
      with the high concentrations of lipids present in the vessel wall and avoids the need for a
      polymer. Results of preclinical and clinical studies have shown that short-term exposure to
      Paclitaxel may suffice to obtain a sustained reduction in late lumen loss and avoid
      restenosis in both coronary and peripheral arteries: in contrast to stents, DCBs do not leave
      any residual material in the artery lumen that could trigger neointimal proliferation, thus
      making DCBs an attractive alternative to stents, especially in challenging arterial
      anatomies. Further investigation is warranted in order to obtain conclusive data.
      Furthermore, the benefit of treating in-stent restenosis (ISR) in the peripheral arteries
      with DCBs has yet to be investigated, although limited data is already available to date.

      The clinical value of these drug-eluting technologies has been proven repeatedly in the
      coronary arteries, and evidence of therapeutic applications to peripheral artery disease is
      starting to build. It is the intent of this prospective study to evaluate the treatment of a
      drug-coated balloon followed by stent implant and comparing this to the results of the 4EVER
      trial and results in the literature.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Primary patency at 12 months
time frame: 12 months
description: Defined as freedom from >50% restenosis as indicated by an independently verified duplex ultrasound peak systolic velocity ratio (PSVR) <2.5 in the target vessel with no reintervention.
measure: Technical success
time frame: 1 day post-op
description: Defined as the ability to cross and stent the lesion to achieve residual angiographic stenosis no greater than 30% and residual stenosis less than 50% by duplex imaging.
measure: Procedural success
time frame: 1 day post-op
description: Defined as the ability to perform the procedure as stated in the protocol, with the Biotronik portfolio.
measure: Number of puncture site complications
time frame: 1 day post-op
measure: Compression time
time frame: 1 day post-op
description: In patients when manual compression is applied to close the puncture site (instead of a closure device).
measure: Primary patency rate at 1-month follow-up
time frame: 1 month
description: Defined as freedom from >50% restenosis as indicated by an independently verified duplex ultrasound peak systolic velocity ratio (PSVR) <2.5 in the target vessel with no re-intervention.
measure: Primary patency rate at 6- and 24-month follow-up
time frame: 6 and 24 months
description: Defined as freedom from >50% restenosis as indicated on a duplex ultrasound with peak systolic velocity ratio (PSVR) <2.5 in the target vessel with no re-intervention.
measure: Freedom from Target Lesion Revascularization (TLR) at at 1-, 6-, 12- and 24-months follow-up
time frame: 1, 6, 12 and 24 months
description: Defined as a repeat intervention to maintain or re-establish patency within the region of the treated arterial vessel plus 5mm proximal an distal to the treated lesion edge.
measure: Clinical success at 1-, 6-, 12- and 24-months follow-up
time frame: 1, 6, 12, 24 months
description: Defined as an improvement of Rutherford classification at 1-, 6-, 12- and 24-month follow-up of one class or more as compared to the pre-procedure Rutherford classification.
measure: Changes in ABI measurements at 1-, 6-, 12- and 24-months
time frame: 1, 6, 12, 24 months
description: Defined as the ankle-brachial index (ABI) measurement difference at 1-, 6-, 12- and 24-months compared to the pre-procedure ABI measurement.
measure: Serious Adverse Events
time frame: up to 24 months
arm group label: Passeo-18-Lux & Pulsar-18
arm group type: Experimental
description: The interventional procedure sequence consists of the following steps:
pre-dilation of the lesion with a Passeo-18 balloon (mandatory)
dilation of the lesion with a Passeo-18 Lux drug releasing balloon (mandatory); a maximum of 2 Passeo-18 Lux balloons can be used per lesion (drug load cannot exceed 12µg)
stenting of the lesion with a Pulsar-18 stent (mandatory)
post-dilation of the lesion with a Passeo-18 balloon (not mandatory)
intervention type: Device
intervention name: Passeo-18 balloon
arm group label: Passeo-18-Lux & Pulsar-18
intervention type: Device
intervention name: Passeo-18 Lux drug releasing balloon
arm group label: Passeo-18-Lux & Pulsar-18
intervention type: Device
intervention name: Pulsar-18 stent
arm group label: Passeo-18-Lux & Pulsar-18
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
responsible party type: Sponsor
mesh term: Vascular Diseases
mesh term: Peripheral Vascular Diseases
mesh term: Peripheral Arterial Disease