<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/NCT03030274</url>
  </required_header>
  <id_info>
    <org_study_id>Occ2016_06</org_study_id>
    <nct_id>NCT03030274</nct_id>
  </id_info>
  <brief_title>The Prelieve Trial - Pilot Study to Assess Safety and Efficacy of a Novel Atrial Flow Regulator (AFR) in Heart Failure Patients</brief_title>
  <acronym>PRELIEVE</acronym>
  <official_title>Prospective, Non-randomized, Pilot Study to Assess Safety and Efficacy of a Novel Atrial Flow Regulator (AFR) in Heart Failure Patients With Reduced Ejection Fraction or in Heart Failure Patients With Preserved Ejection Fraction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Occlutech International AB</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Occlutech International AB</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to investigate safety and efficacy of the Occlutech® AFR device in patients&#xD;
      with HFrEF (Heart failure with reduced ejection fraction) and HFpEF (Heart failure with&#xD;
      preserved ejection fraction)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will enroll subjects with HFrEF or HFpEF, until a maximum of 100 patients have&#xD;
      undergone implantation with the Occlutech® AFR device.&#xD;
&#xD;
      Enrolled patients will be stratified according to their ejection fraction as either HFrEF&#xD;
      (ejection fraction &gt; 15% and &lt;40 %) or HFpEF ( ejection Fraktion &gt; 40 % to 70 %). It is&#xD;
      planned to enroll at least 100 patients per stratification subgroup.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 11, 2017</start_date>
  <completion_date type="Actual">March 2, 2022</completion_date>
  <primary_completion_date type="Actual">May 1, 2021</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>Serious Adverse Device Effects (SADE) within 3 month following implantation.</measure>
    <time_frame>0-3 month</time_frame>
    <description>Incidence of Serious Adverse Device Effects (SADE) following implantation such as:&#xD;
device dislocation / embolization&#xD;
damage to the tricuspid or mitral valve caused by the device&#xD;
intractable arrhythmias caused by the device&#xD;
any circumstances that require device removal.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serious Adverse Device Effects (SADE) between 3-12 month following implantation</measure>
    <time_frame>3-12 month</time_frame>
    <description>Incidence of all Serious Adverse Device Effects (SADE) following implantation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Device placement</measure>
    <time_frame>0-12 month</time_frame>
    <description>Device placement in situ</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left to Right shunt through the AFR device</measure>
    <time_frame>0-12 month</time_frame>
    <description>Evidence of Left to Right shunt through the AFR device</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">106</enrollment>
  <condition>Heart Failure Low Output</condition>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>Occlutech AFR Device</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Prospective, non-randomized, pilot study to assess safety and efficacy of a novel Atrial Flow Regulator in Heart Failure Patients with with reduced Ejection Fraction (HFrEF) and Heart Failure Patients with preserved Ejection Fraction (HFpEF); the AFR-Prelieve Trial</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Occlutech AFR device</intervention_name>
    <description>Catheter-guided placement of an AFR device following balloon atrial septostomy.</description>
    <arm_group_label>Occlutech AFR Device</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria. Each patient must fulfill ALL of the following criteria and details:&#xD;
&#xD;
          1. Age ≥18 years&#xD;
&#xD;
          2. Heart failure resulting in NYHA class III or IV ambulatory&#xD;
&#xD;
          3. Ongoing management of heart failure according to ESC (European Society of Cardiology)&#xD;
             (15) -guidelines during previous ≥6 months&#xD;
&#xD;
          4. Control with Arrhythmia with heart rate &lt;110bpm&#xD;
&#xD;
          5. Life expectancy of at least 1 year&#xD;
&#xD;
          6. The patient should have the ability to fluently speak and understand the language in&#xD;
             which the study is being conducted&#xD;
&#xD;
          7. Written, informed consent by the patient for participation in the study and agreement&#xD;
             to comply with the follow-up schedule&#xD;
&#xD;
          8. Patient has had a successful Balloon Atrial Septostomy (BAS) procedure and is in a&#xD;
             stable hemodynamic state, as assessed by the investigator&#xD;
&#xD;
          9. LVEF ≥15% and ≤ 70% , EF measured via Echocardiography 9.1.9.1. And for LVEF ≥ 40%&#xD;
             (HFpEF): elevated NT-pro-BNP of ≥ 125 pg/ml&#xD;
&#xD;
         10. Elevated left ventricular filling pressure documented by 10.1. Either Pulmonary&#xD;
             capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure at rest ≥&#xD;
             15 mmHg and greater then central venous preassure (CVP) 10.2. 10.2. Or: End-expiratory&#xD;
             PCWP ≥25 mmHg at exercise and CVP &lt;20 mm Hg&#xD;
&#xD;
         11. Transseptal catheterization and femoral vein access is determined to be feasible&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Local or generalized sepsis or other acute infection(s)&#xD;
&#xD;
          2. Any coagulation disorder, if clinically relevant in the opinion of the operator.&#xD;
&#xD;
          3. Allergy to nickel and/or titanium and/or nickel/titanium-based materials, if not&#xD;
             medically manageable&#xD;
&#xD;
          4. Allergy to anti-platelet, -coagulant, or -thrombotic therapy, if not medically&#xD;
             manageable&#xD;
&#xD;
          5. Intolerance to contrast agents, if not medically manageable&#xD;
&#xD;
          6. Participation in another medical trial testing a therapy less than 30 days before the&#xD;
             intended AFR implantation procedure&#xD;
&#xD;
          7. Trans-oesophageal echocardiography and / or use of general anaesthetic is&#xD;
             contraindicated&#xD;
&#xD;
          8. Breast feeding women&#xD;
&#xD;
          9. Pregnancy&#xD;
&#xD;
             Processes which would technically disturb the safe intervention as planned:&#xD;
&#xD;
         10. Occluded inferior vena cava access&#xD;
&#xD;
         11. History of ASD and/or atrial septal repair or closure device in place&#xD;
&#xD;
         12. Intracardiac thrombus&#xD;
&#xD;
             Clinical conditions:&#xD;
&#xD;
         13. Moderate valvular diseases requiring therapy according to current ESC guidelines.&#xD;
             Patients are eligible in case therapy is formally indicated but cannot be performed&#xD;
             due to technical or medial reasons if the latter is confirmed in writing by the PI in&#xD;
             mutual agreement with the heart team and Severe aortic stenosis with valve area &lt;&#xD;
             1.5cm² and Severe AR, TR or MR. Classification of severity of regurgitation should&#xD;
             follow the definition provided in Lancelotti et al, Eur Heart J Cardiovasc Imaging&#xD;
             2013 [22]&#xD;
&#xD;
         14. Patients who has unstable and intractable angina pectoris&#xD;
&#xD;
         15. Evidence of right heart failure defined as (by ECHO)&#xD;
&#xD;
               1. Severe Right Ventricular Dysfunction (TAPSE &lt; 14 mm)&#xD;
&#xD;
               2. Severe Right Ventricular Dilatation (RV volume ≥ LV volume)&#xD;
&#xD;
               3. Severe pulmonary hypertension (PASP &gt; 60 mm Hg)&#xD;
&#xD;
         16. Active malignancy&#xD;
&#xD;
         17. Severe valve disease, or implanted mechanical valve prosthesis&#xD;
&#xD;
         18. Congenital heart defect&#xD;
&#xD;
         19. Large PFO with significant atrial septal aneurysm (bubble test shows more than 20&#xD;
             bubbles)&#xD;
&#xD;
         20. Inability to perform 6-minutes walking test&#xD;
&#xD;
         21. Clinically relevant thrombocytopenia, thrombocytosis, leukopenia, or anemia&#xD;
&#xD;
         22. Symptomatic carotid artery disease&#xD;
&#xD;
         23. Mitral valve stenosis&#xD;
&#xD;
         24. Has any condition that, in the opinion of the Investigator, might interfere with the&#xD;
             Implantation, might affect the patients well-being thereafter or might interfere with&#xD;
             the conduct of the study&#xD;
&#xD;
         25. Systolic blood pressure of &gt;170 mmHg, despite medical therapy&#xD;
&#xD;
         26. Severe lung disease (causing PHT with systolic PAP &gt;60mmHg)&#xD;
&#xD;
         27. Pulmonary Hypertension (Systolic PAP &gt;60mmHg)&#xD;
&#xD;
         28. TIA or stroke within the last 6 months&#xD;
&#xD;
         29. Scheduled for heart transplantation&#xD;
&#xD;
         30. Bleeding disorders (INR &gt; 2.0, Thrombocytes &lt; 100.000, Hemoglobin &lt;8.0 gr/dl)&#xD;
&#xD;
         31. Myocardial infarction or percutaneous intervention or CABG (all within the last 3&#xD;
             month) or indication for a coronary intervention&#xD;
&#xD;
         32. Resyncronization therapy started within the last 6 months&#xD;
&#xD;
         33. Aneurysm of the septum&#xD;
&#xD;
         34. Hypertrophied Inter Atrial Septum (IAS) &gt; 10mm depth&#xD;
&#xD;
         35. Hypertrophic Obstructive Cardiomyopathy (HOCM) or infiltrative CM as cause of HF&#xD;
&#xD;
         36. Thromboembolic events within the last 6 months&#xD;
&#xD;
         37. Dialysis and renal insufficiency requiring dialysis&#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>AZ Maria Middelares</name>
      <address>
        <city>Gent</city>
        <state>Buitenring Sint-Denijs 30</state>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <state>Herestraat 49</state>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Brussels</name>
      <address>
        <city>Brussels</city>
        <state>Laarbeeklaan 101</state>
        <zip>1090</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Algemeen Stedelijk Ziekenhuis (Asz)</name>
      <address>
        <city>Aalst</city>
        <state>Merestraat 80</state>
        <zip>9300</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OLV (Onze-Lieve-Vrouwziekenhuis) Hospital Aalst</name>
      <address>
        <city>Aalst</city>
        <state>Moorselbaan 164</state>
        <zip>9300</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charité - Universitätsmedizin Berlin</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vivantes Klinikum im Friedrichshain</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Herzzentrum Uniklinik Köln</name>
      <address>
        <city>Cologne</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CardioVasculäres Centrum Frankfurt</name>
      <address>
        <city>Frankfurt</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cardiologicum Hamburg</name>
      <address>
        <city>Hamburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Hochschule Hannover</name>
      <address>
        <city>Hannover</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Homburg</name>
      <address>
        <city>Homburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Herzzentrum Leipzig</name>
      <address>
        <city>Leipzig</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniklinikum Magdeburg A. ö. R.</name>
      <address>
        <city>Magdeburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsmedizin Rostock</name>
      <address>
        <city>Rostock</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Würzburg</name>
      <address>
        <city>Würzburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi</name>
      <address>
        <city>Ankara</city>
        <state>Altındağ</state>
        <zip>06110</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hacettepe Üni Hastanesi</name>
      <address>
        <city>Ankara</city>
        <state>Altındağ</state>
        <zip>06230</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ege Üniversitesi Hastanesi</name>
      <address>
        <city>İzmir</city>
        <state>Bornova</state>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>İstanbul Üniversitesi</name>
      <address>
        <city>Istanbul</city>
        <state>Fatih</state>
        <zip>34452</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kartal Koşuyolu Yüksek İhtisas Eğitim ve Araştırma Hastanesi</name>
      <address>
        <city>Istanbul</city>
        <state>Kartal</state>
        <zip>34865</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tepecik Eğitim Ve Araştırma Hastanesi</name>
      <address>
        <city>İzmir</city>
        <state>Konak</state>
        <zip>35020</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sivas Cumhuriyet Üniversitesi Tıp Fakültesi Araştırma ve Uygulama Hastanesi</name>
      <address>
        <city>Sivas</city>
        <state>Merkez</state>
        <zip>58140</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bezmialem University</name>
      <address>
        <city>Istanbul</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kocaeli Üniversitesi Hastanesi</name>
      <address>
        <city>Kocaeli</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>İzmir Kâtip Çelebi Üniversitesi</name>
      <address>
        <city>İzmir</city>
        <state>Çiğli</state>
        <zip>35620</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Germany</country>
    <country>Turkey</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>January 17, 2017</study_first_submitted>
  <study_first_submitted_qc>January 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 24, 2017</study_first_posted>
  <last_update_submitted>September 13, 2022</last_update_submitted>
  <last_update_submitted_qc>September 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 15, 2022</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>Heart Failure</mesh_term>
  </condition_browse>
  <study_docs>
    <study_doc>
      <doc_id>NCT03030274</doc_id>
      <doc_type>Publications</doc_type>
      <doc_url>http://pubmed.ncbi.nlm.nih.gov/31130524/</doc_url>
      <doc_comment>Christina Paitazoglou 1, Ramazan Özdemir, Roman Pfister, Martin W Bergmann, Jozef Bartunek, Teoman Kilic, Alexander Lauten, Alexander Schmeisser, Mehdi Zoghi, Stefan Anker, Horst Sievert, Felix Mahfoud_The AFR-PRELIEVE trial: a prospective, non-randomised, pilot study to assess the Atrial Flow Regulator (AFR) in heart failure patients with either preserved or reduced ejection fraction</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>NCT03030274</doc_id>
      <doc_type>Publications</doc_type>
      <doc_url>http://pubmed.ncbi.nlm.nih.gov/33555114/</doc_url>
      <doc_comment>Christina Paitazoglou 1, Martin W Bergmann 1, Ramazan Özdemir 2, Roman Pfister 3, Jozef Bartunek 4, Teoman Kilic 5, Alexander Lauten 6, Alexander Schmeisser 7, Mehdi Zoghi 8, Stefan D Anker 6, Horst Sievert 9, Felix Mahfoud 10, AFR-PRELIEVE Investigators_One-year results of the first-in-man study investigating the Atrial Flow Regulator for left atrial shunting in symptomatic heart failure patients: the PRELIEVE study</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>NCT03030274</doc_id>
      <doc_type>Publiactions</doc_type>
      <doc_url>http://pubmed.ncbi.nlm.nih.gov/34763641/</doc_url>
      <doc_comment>Nijad Bakhshaliyev 1, Ramazan Ozdemir 1_The impact of atrial flow regulator implantation on hemodynamic parameters in patients with heart failure</doc_comment>
    </study_doc>
  </study_docs>
  <!-- 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/NCT03030274
org study id: Occ2016_06
nct id: NCT03030274
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This study aims to investigate safety and efficacy of the Occlutech® AFR device in patients
      with HFrEF (Heart failure with reduced ejection fraction) and HFpEF (Heart failure with
      preserved ejection fraction)
This study will enroll subjects with HFrEF or HFpEF, until a maximum of 100 patients have
      undergone implantation with the Occlutech® AFR device.

      Enrolled patients will be stratified according to their ejection fraction as either HFrEF
      (ejection fraction > 15% and <40 %) or HFpEF ( ejection Fraktion > 40 % to 70 %). It is
      planned to enroll at least 100 patients per stratification subgroup.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Serious Adverse Device Effects (SADE) within 3 month following implantation.
time frame: 0-3 month
description: Incidence of Serious Adverse Device Effects (SADE) following implantation such as:
device dislocation / embolization
damage to the tricuspid or mitral valve caused by the device
intractable arrhythmias caused by the device
any circumstances that require device removal.
measure: Serious Adverse Device Effects (SADE) between 3-12 month following implantation
time frame: 3-12 month
description: Incidence of all Serious Adverse Device Effects (SADE) following implantation
measure: Device placement
time frame: 0-12 month
description: Device placement in situ
measure: Left to Right shunt through the AFR device
time frame: 0-12 month
description: Evidence of Left to Right shunt through the AFR device
arm group label: Occlutech AFR Device
arm group type: Experimental
description: Prospective, non-randomized, pilot study to assess safety and efficacy of a novel Atrial Flow Regulator in Heart Failure Patients with with reduced Ejection Fraction (HFrEF) and Heart Failure Patients with preserved Ejection Fraction (HFpEF); the AFR-Prelieve Trial
intervention type: Device
intervention name: Occlutech AFR device
description: Catheter-guided placement of an AFR device following balloon atrial septostomy.
arm group label: Occlutech AFR Device
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: Belgium
country: Germany
country: Turkey
responsible party type: Sponsor
mesh term: Heart Failure
study doc: 
study doc: 
study doc: 