<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/NCT03243890</url>
  </required_header>
  <id_info>
    <org_study_id>AVADEC</org_study_id>
    <nct_id>NCT03243890</nct_id>
  </id_info>
  <brief_title>The Aortic Valve DECalcification (AVADEC) Trial</brief_title>
  <acronym>AVADEC</acronym>
  <official_title>The Effects of Menaquinone-7 Supplementation in Patients With Aortic Valves Calcification</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Axel Diederichsen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Odense University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Aortic stenosis is a common heart valve disease and due to the growing elderly population the&#xD;
      prevalence is increasing. The disease is progressive with increasing calcification of the&#xD;
      valve cusps. A few attempts with medical preventive treatment have failed, thus presently the&#xD;
      only effective treatment of aortic stenosis is surgery. This study will examine the effect of&#xD;
      menaquinone-7 (MK-7) supplementation on progression of aortic valve calcification (AVC). The&#xD;
      investigators hypothesize that MK-7 supplementation will slow down the calcification process.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 12, 2018</start_date>
  <completion_date type="Actual">May 1, 2021</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>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Subjects will be randomized 1:1 after stratiﬁcation for site, AVC score (300-599 or ≥600) and statin-use. Each site will be provided with sequentially numbered, opaque and sealed envelopes containing randomly generated treatment allocations. Four different types of envelopes are provided; 1) AVC 300-599, no statin-use; 2) AVC 300-599, statin-use; 3) AVC ≥600, no statin-use; and 4) AVC ≥600, statin-use.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>The randomization-list is available to the data and safety monitoring board, but patients, nurses, physicians and other data collectors are kept blinded to the allocation during the study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Aortic valve calcification</measure>
    <time_frame>From baseline to two years of follow-up</time_frame>
    <description>The primary endpoint is the change in aortic valve calcification. The natural history of the aortic valve calcification is not adequately understood, and accordingly the changes are analyzed in two prespecified patient subgroups (AVC score 300-599 and ≥600, respectively).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Arterial calcification</measure>
    <time_frame>From baseline to two years of follow-up</time_frame>
    <description>Change in compiled arterial calcification by non-contrast CT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aortic size</measure>
    <time_frame>From baseline to two years of follow-up</time_frame>
    <description>Change in aortic diameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coronary plaque composition</measure>
    <time_frame>From baseline to two years of follow-up</time_frame>
    <description>Change in total plaque burden in the coronaries and carotid arteries by contrast CT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aortic valve area</measure>
    <time_frame>From baseline to two years of follow-up</time_frame>
    <description>Change in aortic valve area by transthoracic echocardiography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bone mineral density</measure>
    <time_frame>From baseline to two years of follow-up</time_frame>
    <description>Change in bone mineral density as quantitative CT of the columna lumbalis and hip region</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers of calcification</measure>
    <time_frame>From baseline to two years of follow-up</time_frame>
    <description>Change in matrix-Gla proteins and osteocalcin with different phosphorylation (p and dp) and carboxylation forms (c and uc).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
    <time_frame>From baseline to two years of follow-up</time_frame>
    <description>Change in quality of life</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">389</enrollment>
  <condition>Aortic Valve Stenosis</condition>
  <condition>Multidetector Computed Tomography</condition>
  <condition>Vitamin K 2</condition>
  <condition>Randomised Clinical Trial</condition>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Study drug. Supplementation with MK-7 (720 µg/day) including the recommended daily dose of vitamin D (25 µg/day)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo tablet (no active treatment). The placebo tablet is matched to the study drug for taste, color, and size.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Menaquinone-7 720 µg/day including the recommended daily dose of vitamin D (25 µg/day).</intervention_name>
    <description>Half of the patients are randomized to supplementation with MK-7 (720 µg/day) including the recommended daily dose of vitamin D (25 µg/day).</description>
    <arm_group_label>Intervention</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Half of the patients are randomized to placebo treatment (no active treatment).</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Participants in the Danish Cardiovascular Screening Trial (Trials. 2015 Dec 5;16:554) with&#xD;
        an aortic valve calcification score above 300, but without aortic valve stenosis are&#xD;
        eligible.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known aortic valve disease (peak velocity ≥3.0 m/s)&#xD;
&#xD;
          -  History of venous thrombosis or other coagulation disorders or use of vitamin K&#xD;
             antagonists&#xD;
&#xD;
          -  Disorders of calcium and phosphate metabolism&#xD;
&#xD;
          -  A life-expectancy &lt; 5 years&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Axel CP Diederichsen, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Odense University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Cardiology, Odense University Hospital</name>
      <address>
        <city>Odense</city>
        <state>Odense C</state>
        <zip>DK-5000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <link>
    <url>https://bmjopen.bmj.com/content/8/8/e022019.long</url>
    <description>Protocol</description>
  </link>
  <reference>
    <citation>Lindholt JS, Frandsen NE, Fredgart MH, Ovrehus KA, Dahl JS, Moller JE, Folkestad L, Urbonaviciene G, Becker SW, Lambrechtsen J, Auscher S, Hosbond S, Alan DH, Rasmussen LM, Gerke O, Mickley H, Diederichsen A. Effects of menaquinone-7 supplementation in patients with aortic valve calcification: study protocol for a randomised controlled trial. BMJ Open. 2018 Aug 23;8(8):e022019. doi: 10.1136/bmjopen-2018-022019.</citation>
    <PMID>30139903</PMID>
  </reference>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>August 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 9, 2017</study_first_posted>
  <last_update_submitted>September 28, 2022</last_update_submitted>
  <last_update_submitted_qc>September 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Odense University Hospital</investigator_affiliation>
    <investigator_full_name>Axel Diederichsen</investigator_full_name>
    <investigator_title>Associated professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aortic Valve Stenosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D</mesh_term>
    <mesh_term>Vitamin K 2</mesh_term>
    <mesh_term>Vitamin K</mesh_term>
    <mesh_term>Menaquinone 7</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 24, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/90/NCT03243890/SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03243890
org study id: AVADEC
nct id: NCT03243890
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Aortic stenosis is a common heart valve disease and due to the growing elderly population the
      prevalence is increasing. The disease is progressive with increasing calcification of the
      valve cusps. A few attempts with medical preventive treatment have failed, thus presently the
      only effective treatment of aortic stenosis is surgery. This study will examine the effect of
      menaquinone-7 (MK-7) supplementation on progression of aortic valve calcification (AVC). The
      investigators hypothesize that MK-7 supplementation will slow down the calcification process.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Subjects will be randomized 1:1 after stratiﬁcation for site, AVC score (300-599 or ≥600) and statin-use. Each site will be provided with sequentially numbered, opaque and sealed envelopes containing randomly generated treatment allocations. Four different types of envelopes are provided; 1) AVC 300-599, no statin-use; 2) AVC 300-599, statin-use; 3) AVC ≥600, no statin-use; and 4) AVC ≥600, statin-use.
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: The randomization-list is available to the data and safety monitoring board, but patients, nurses, physicians and other data collectors are kept blinded to the allocation during the study.
measure: Aortic valve calcification
time frame: From baseline to two years of follow-up
description: The primary endpoint is the change in aortic valve calcification. The natural history of the aortic valve calcification is not adequately understood, and accordingly the changes are analyzed in two prespecified patient subgroups (AVC score 300-599 and ≥600, respectively).
measure: Arterial calcification
time frame: From baseline to two years of follow-up
description: Change in compiled arterial calcification by non-contrast CT
measure: Aortic size
time frame: From baseline to two years of follow-up
description: Change in aortic diameter
measure: Coronary plaque composition
time frame: From baseline to two years of follow-up
description: Change in total plaque burden in the coronaries and carotid arteries by contrast CT
measure: Aortic valve area
time frame: From baseline to two years of follow-up
description: Change in aortic valve area by transthoracic echocardiography
measure: Bone mineral density
time frame: From baseline to two years of follow-up
description: Change in bone mineral density as quantitative CT of the columna lumbalis and hip region
measure: Biomarkers of calcification
time frame: From baseline to two years of follow-up
description: Change in matrix-Gla proteins and osteocalcin with different phosphorylation (p and dp) and carboxylation forms (c and uc).
measure: Quality of life
time frame: From baseline to two years of follow-up
description: Change in quality of life
arm group label: Intervention
arm group type: Experimental
description: Study drug. Supplementation with MK-7 (720 µg/day) including the recommended daily dose of vitamin D (25 µg/day)
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo tablet (no active treatment). The placebo tablet is matched to the study drug for taste, color, and size.
intervention type: Dietary Supplement
intervention name: Menaquinone-7 720 µg/day including the recommended daily dose of vitamin D (25 µg/day).
description: Half of the patients are randomized to supplementation with MK-7 (720 µg/day) including the recommended daily dose of vitamin D (25 µg/day).
arm group label: Intervention
intervention type: Dietary Supplement
intervention name: Placebo
description: Half of the patients are randomized to placebo treatment (no active treatment).
arm group label: Placebo
criteria: 
gender: Male
minimum age: 65 Years
maximum age: 75 Years
healthy volunteers: No
last name: Axel CP Diederichsen, PhD
role: Principal Investigator
affiliation: Odense University Hospital
facility: 
country: Denmark
url: https://bmjopen.bmj.com/content/8/8/e022019.long
description: Protocol
citation: Lindholt JS, Frandsen NE, Fredgart MH, Ovrehus KA, Dahl JS, Moller JE, Folkestad L, Urbonaviciene G, Becker SW, Lambrechtsen J, Auscher S, Hosbond S, Alan DH, Rasmussen LM, Gerke O, Mickley H, Diederichsen A. Effects of menaquinone-7 supplementation in patients with aortic valve calcification: study protocol for a randomised controlled trial. BMJ Open. 2018 Aug 23;8(8):e022019. doi: 10.1136/bmjopen-2018-022019.
PMID: 30139903
responsible party type: Sponsor-Investigator
investigator affiliation: Odense University Hospital
investigator full name: Axel Diederichsen
investigator title: Associated professor
mesh term: Aortic Valve Stenosis
mesh term: Vitamin D
mesh term: Vitamin K 2
mesh term: Vitamin K
mesh term: Menaquinone 7
provided document: 