<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/NCT01687075</url>
  </required_header>
  <id_info>
    <org_study_id>Create</org_study_id>
    <nct_id>NCT01687075</nct_id>
  </id_info>
  <brief_title>CRE8 in All Comers Patients</brief_title>
  <official_title>CRE8 in All Comers Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tel-Aviv Sourasky Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tel-Aviv Sourasky Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to evaluate clinical performances of Cre8 in all comer population&#xD;
      in Subjects over 18 years old who are undergoing a clinically indicated coronary angiogram&#xD;
      and angioplasty on de-novo lesion located in native coronary arteries&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The development, clinical validation, and widespread use of drug-eluting stents have&#xD;
      revolutionized the treatment of patients with coronary artery disease. Large scale,&#xD;
      prospective, multicenter double-blind randomized trials have provided strong evidence that&#xD;
      sirolimus-eluting stents, paclitaxel-eluting stents, and zotarolimus-eluting stents&#xD;
      significantly reduce angiographic restenosis and enhance event-free survival compared with&#xD;
      bare-metal stents after implantation in native coronary arteries1. However, higher rates of&#xD;
      late and very late stent thrombosis with SES and PES, likely due to delayed and incomplete&#xD;
      endothelialization compared with BMS, have raised safety concerns with DES as a class.&#xD;
      Therefore, alongside clinical investigations, histopathological evaluations were conducted on&#xD;
      the coronary arteries of patients who died after DES implantation to examine the healing&#xD;
      status of the vessel. The evidence obtained suggested that the polymer components used to&#xD;
      carry the drug in the first generation of DES may be associated with a local inflammatory&#xD;
      response, associated with localized hypersensitivity and eosinophil infiltration, with&#xD;
      consequent alteration of the vessel wall and delay in the formation of the endothelium.&#xD;
      Because specific stent design and/or polymer features may impact DES performance, numerous&#xD;
      studies have focused on the comparative assessment of various DES, with conflicting results.&#xD;
&#xD;
      The clinical need thus exists for enhanced stent designs which offer improved safety and&#xD;
      efficacy profiles compared to the earlier stent platforms.&#xD;
&#xD;
      new technologies have been developed which have led to the creation of devices with delivery&#xD;
      systems based on the use of more biocompatible or bioabsorbable polymers and cytostatic drugs&#xD;
      similar to sirolimus. The clinical data obtained with this second generation have&#xD;
      demonstrated, in all devices tested, no less efficacy than first-generation DES, and a better&#xD;
      safety profile, although not statistically significant.Concerning the most widely used second&#xD;
      generation DES,after a small first-in-man trial, its safety and efficacy was further studied&#xD;
      in larger randomized trials on patients with non-complex lesions in which EES was compared to&#xD;
      PES, proving its angiographic superiority and clinical non-inferiority. A step forward, in&#xD;
      assessing the clinically significant differences among different DES, was done with a new&#xD;
      randomized trial comparing EES versus PES, powered for testing superiority in clinical&#xD;
      outcomes and of sufficient magnitude to provide data on patient subgroups, particularly&#xD;
      patients with diabetes. At present, a third-generation of DES, developed to minimize the&#xD;
      possible side effects related to the presence of the polymer, is being evaluated in humans.&#xD;
      To avoid the presence of the polymer on the surface of the device, different platforms are&#xD;
      being evaluated: those with a porous surface onto which the pure drug is placed and those&#xD;
      with holes closed towards the intraluminal part by a bioabsorbable polymer, onto which the&#xD;
      drug is loaded. A third option to avoid the need of polymers has been used in the new CRE8&#xD;
      DES, featuring a polymer free platform with abluminal reservoirs to release the Amphilimus&#xD;
      formulation. This device has been tested against Taxus Liberté in a randomized clinical&#xD;
      trial, to assess the non-inferiority angiographic efficacy results. The 6month angiographic&#xD;
      analysis, demonstrates that the primary study endpoint has been achieved, showing that CRE8&#xD;
      was not inferior to Taxus Liberté in terms of efficacy performances.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">August 2014</completion_date>
  <primary_completion_date type="Actual">July 2014</primary_completion_date>
  <phase>N/A</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>Incidence of 6-month device-oriented clinical composite endpoint, defined as Cardiac death / Target vessel MI / Clinically indicated TLR</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of clinical composite endpoints at 30 days, 1 year from the index procedure</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">215</enrollment>
  <condition>Consecutive Subjects Who Are Suitable for a Coronary</condition>
  <condition>Angioplasty of de Novo Lesion(s) in Native Coronary</condition>
  <condition>Arteries Should be Screened for Eligibility.</condition>
  <condition>A Total Number of 200 Patients Fulfilling the Selection</condition>
  <condition>Criteria and Willing to Sign the Informed Consent Should</condition>
  <condition>be Enrolled in the Trial.</condition>
  <arm_group>
    <arm_group_label>CR8</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>a drug eluting coronary device, made of Cobalt-Chromium alloy and integrally coated with i-Carbofilm™, loaded with formulated Sirolimus</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>CR8 a drug eluting coronary stent</intervention_name>
    <description>a drug eluting coronary device, made of Cobalt-Chromium alloy and integrally coated with i-Carbofilm™, loaded with formulated Sirolimus</description>
    <arm_group_label>CR8</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age over 18 years&#xD;
&#xD;
          -  Patients with symptoms of stable angina or documented silent ischemia&#xD;
&#xD;
          -  Patient with coronary artery disease ranging between 0 and 22 according to the Syntax&#xD;
             score&#xD;
&#xD;
          -  Patients with acute coronary syndrome, including unstable angina, NSTEMI and STEMI&#xD;
&#xD;
          -  Patient is eligible for percutaneous coronary intervention and is an acceptable&#xD;
             candidate for surgical revascularization&#xD;
&#xD;
          -  Left ventricular ejection fraction &gt; 30%;&#xD;
&#xD;
          -  Target de-novo lesions with diameter stenosis &gt; 50% (including total occlusion)&#xD;
&#xD;
          -  Target lesion located in a target vessel with a diameter ranging from 2.5 to 4.0 mm;&#xD;
&#xD;
          -  patient has been informed of the nature of the study and agrees to its provisions and&#xD;
             has provided written informed consent as approved by the Ethical Committee of the&#xD;
             respective clinical site.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female with childbearing potential or lactating;&#xD;
&#xD;
          -  Known allergies to antiplatelets, anticoagulants, contrast media, sirolimus or cobalt&#xD;
             chromium;&#xD;
&#xD;
          -  Acute or chronic renal dysfunction (defined as creatinine greater than 2.5 mg/dl or on&#xD;
             dialysis);&#xD;
&#xD;
          -  Thrombocytopenia (platelet count less than 100,000/mm³) or hypercoagulable disorder;&#xD;
&#xD;
          -  Known significant gastro-intestinal or urinary bleeding within the past 6 months;&#xD;
&#xD;
          -  Patient refusing blood transfusion;&#xD;
&#xD;
          -  Patient currently under immunosuppressant therapy;&#xD;
&#xD;
          -  Patient with planned surgery within 6 months from the index procedure unless dual&#xD;
             antiplatelet therapy is maintained throughout the peri-surgical period;&#xD;
&#xD;
          -  Co-morbidities that could interfere with completion of study procedures, or life&#xD;
             expectancy less than 1 year;&#xD;
&#xD;
          -  Participating in another investigational drug or device trial that has not completed&#xD;
             the primary endpoint or would interfere with the endpoints of this study;&#xD;
&#xD;
          -  Patient underwent target vessel revascularization, with a DES, within 3 months prior&#xD;
             to the index procedure;&#xD;
&#xD;
          -  Target lesion is located or supplied by an arterial or venous bypass graft&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shmuel Banai, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tel Aviv Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tel Aviv Sourasky Medical Center</name>
      <address>
        <city>Tel Aviv</city>
        <zip>64329</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>June 2016</verification_date>
  <study_first_submitted>September 13, 2012</study_first_submitted>
  <study_first_submitted_qc>September 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 18, 2012</study_first_posted>
  <last_update_submitted>June 27, 2016</last_update_submitted>
  <last_update_submitted_qc>June 27, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 28, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Tel-Aviv Sourasky Medical Center</investigator_affiliation>
    <investigator_full_name>michal roll</investigator_full_name>
    <investigator_title>Prof. Shmuel Banai</investigator_title>
  </responsible_party>
  <keyword>coronary angioplasty</keyword>
  <keyword>de novo lesion</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT01687075
org study id: Create
nct id: NCT01687075
lead sponsor: 
has dmc: No
The purpose of the study is to evaluate clinical performances of Cre8 in all comer population
      in Subjects over 18 years old who are undergoing a clinically indicated coronary angiogram
      and angioplasty on de-novo lesion located in native coronary arteries
The development, clinical validation, and widespread use of drug-eluting stents have
      revolutionized the treatment of patients with coronary artery disease. Large scale,
      prospective, multicenter double-blind randomized trials have provided strong evidence that
      sirolimus-eluting stents, paclitaxel-eluting stents, and zotarolimus-eluting stents
      significantly reduce angiographic restenosis and enhance event-free survival compared with
      bare-metal stents after implantation in native coronary arteries1. However, higher rates of
      late and very late stent thrombosis with SES and PES, likely due to delayed and incomplete
      endothelialization compared with BMS, have raised safety concerns with DES as a class.
      Therefore, alongside clinical investigations, histopathological evaluations were conducted on
      the coronary arteries of patients who died after DES implantation to examine the healing
      status of the vessel. The evidence obtained suggested that the polymer components used to
      carry the drug in the first generation of DES may be associated with a local inflammatory
      response, associated with localized hypersensitivity and eosinophil infiltration, with
      consequent alteration of the vessel wall and delay in the formation of the endothelium.
      Because specific stent design and/or polymer features may impact DES performance, numerous
      studies have focused on the comparative assessment of various DES, with conflicting results.

      The clinical need thus exists for enhanced stent designs which offer improved safety and
      efficacy profiles compared to the earlier stent platforms.

      new technologies have been developed which have led to the creation of devices with delivery
      systems based on the use of more biocompatible or bioabsorbable polymers and cytostatic drugs
      similar to sirolimus. The clinical data obtained with this second generation have
      demonstrated, in all devices tested, no less efficacy than first-generation DES, and a better
      safety profile, although not statistically significant.Concerning the most widely used second
      generation DES,after a small first-in-man trial, its safety and efficacy was further studied
      in larger randomized trials on patients with non-complex lesions in which EES was compared to
      PES, proving its angiographic superiority and clinical non-inferiority. A step forward, in
      assessing the clinically significant differences among different DES, was done with a new
      randomized trial comparing EES versus PES, powered for testing superiority in clinical
      outcomes and of sufficient magnitude to provide data on patient subgroups, particularly
      patients with diabetes. At present, a third-generation of DES, developed to minimize the
      possible side effects related to the presence of the polymer, is being evaluated in humans.
      To avoid the presence of the polymer on the surface of the device, different platforms are
      being evaluated: those with a porous surface onto which the pure drug is placed and those
      with holes closed towards the intraluminal part by a bioabsorbable polymer, onto which the
      drug is loaded. A third option to avoid the need of polymers has been used in the new CRE8
      DES, featuring a polymer free platform with abluminal reservoirs to release the Amphilimus
      formulation. This device has been tested against Taxus Liberté in a randomized clinical
      trial, to assess the non-inferiority angiographic efficacy results. The 6month angiographic
      analysis, demonstrates that the primary study endpoint has been achieved, showing that CRE8
      was not inferior to Taxus Liberté in terms of efficacy performances.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of 6-month device-oriented clinical composite endpoint, defined as Cardiac death / Target vessel MI / Clinically indicated TLR
time frame: 6 months
measure: Incidence of clinical composite endpoints at 30 days, 1 year from the index procedure
time frame: 1 year
arm group label: CR8
arm group type: Experimental
description: a drug eluting coronary device, made of Cobalt-Chromium alloy and integrally coated with i-Carbofilm™, loaded with formulated Sirolimus
intervention type: Device
intervention name: CR8 a drug eluting coronary stent
description: a drug eluting coronary device, made of Cobalt-Chromium alloy and integrally coated with i-Carbofilm™, loaded with formulated Sirolimus
arm group label: CR8
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Shmuel Banai, Prof
role: Principal Investigator
affiliation: Tel Aviv Medical Center
facility: 
country: Israel
responsible party type: Principal Investigator
investigator affiliation: Tel-Aviv Sourasky Medical Center
investigator full name: michal roll
investigator title: Prof. Shmuel Banai
sharing ipd: No