<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/NCT03239509</url>
  </required_header>
  <id_info>
    <org_study_id>ANDALVALVE STUDY</org_study_id>
    <nct_id>NCT03239509</nct_id>
  </id_info>
  <brief_title>15 Years Outcomes Following Bioprosthetic vs Mechanical Aortic Valve Replacement Between 50-65 Years</brief_title>
  <acronym>ANDALVALVE</acronym>
  <official_title>15 Years Outcomes Following Bioprosthetic vs Mechanical Isolated Aortic Valve Replacement for Aortic Stenosis in Patients Aged 50 to 65 Years in South Spain. The Andalousian Aortic Valve Multicentric Study (ANDALVALVE)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud</source>
  <oversight_info>
    <has_dmc>No</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>
      Currently there is an increase in the use of bioprosthesis worldwide (&gt; 70% according to&#xD;
      national data of the Spanish Society of Thoracic and Cardiovascular Surgery).&#xD;
&#xD;
      There is conflicting evidence regarding the long-term survival of patients aged 50-65 years&#xD;
      with mechanical (M) or biological (B) aortic prostheses. General consensus of greater&#xD;
      complications associated with the use of long-life anticoagulation in M and of reoperation in&#xD;
      B.&#xD;
&#xD;
      Similar survival with lower MACCE complications in bioprosthesis could reconsider their&#xD;
      choice in patients aged 50-65 years, specially in the current TAVI era.&#xD;
&#xD;
      The investigators are going to perform a multicentric retrospective observational study&#xD;
      (Registry) about 15 year-outcomes Following Bioprosthetic vs Mechanical Isolated Aortic Valve&#xD;
      Replacement for Aortic Stenosis in Patients Aged 50 to 65 Years in 5 Cardiovascular Surgery&#xD;
      Centers in Andalousia (south Spain)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives The main objective is to analyze long-term survival (15 years) and major&#xD;
      cardiovascular complications (MACE, (death of any cause, neurological events (TIA / stroke),&#xD;
      any prosthesis reoperation, and major bleeding), in patients aged 50-65 years who underwent&#xD;
      isolated aortic valve replacement (AVR) due to severe aortic stenosis . Secondary objectives&#xD;
      were to analyze the evolution of transprosthetic gradients by echocardiography, type of INR&#xD;
      control, and degree of significant structural degeneration in bioprostheses.&#xD;
&#xD;
      Material and Method: A retrospective analytical study of patients aged 50-65 years who&#xD;
      underwent AVR surgery for stenosis between 2000-2015 in all centers with a Cardiovascular&#xD;
      Surgery Dept. in Andalousia (SPAIN) as an inclusion criterion. As exclusion criteria,&#xD;
      autonomic change of residence, need for concomitant surgery, previous cardiac interventions&#xD;
      and endocarditis. Survival analysis and clinical data will be performed through the Diraya&#xD;
      Health Care medical records (DAE), direct telephone contact with family and / or relatives, A&#xD;
      crude analysis of the data and a posterior analysis by propensity score matching with the&#xD;
      help of the Foundation for Biomedical Research of Malaga (IBIMA) with SPSS software will be&#xD;
      carried out using a 1: 1 &quot;nearest neighbour&quot; matching protocol based on the Number of total&#xD;
      bioprosthesis. A total sample of more than 1200 cases is expected, of which about 380 would&#xD;
      be bioprostheses that would serve as a basis for the pairing. To find a 10% difference in the&#xD;
      primary endpoint, two groups of 325 patients are required for a p = 0.05 and 80% for a&#xD;
      bilateral contrast of two independent proportions. Sub-analysis will be performed by&#xD;
      subgroups of age (50-59 vs. 60-65 years) and another according to the mark of the 2&#xD;
      prostheses of each type most used. All statistical analyzes will be two-tailed with an alpha&#xD;
      error of 0.05 to consider statistically significant data, and will be reviewed by IBIMA&#xD;
      biostatistics.&#xD;
&#xD;
      Conclusions: A positive result (similar survival and prosthetic durability in group B, with&#xD;
      lower complications) could change the current indications of AVS in our environment, allowing&#xD;
      the age of indication of bioprostheses to be reduced below 60 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">April 2018</completion_date>
  <primary_completion_date type="Actual">April 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants alive</measure>
    <time_frame>From date of surgery until the date of death from any cause, assessed up to 17 years</time_frame>
    <description>Survival since surgery</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Late postoperative endpoint of 4 MACE complications</measure>
    <time_frame>From date of surgery until the date of first documented MACE (see description) or date of death from any cause, whichever came first, assessed up to 17 years</time_frame>
    <description>All cause Mortality, major bleeding, cerebrovascular or transient ischemic accident, and need of any prosthesis reintervention (Major Adverse Cardiovascular Events, MACE)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total in-Hospital and Intensive Care Unit stay (in days)</measure>
    <time_frame>From date of surgery to discharge of the unit and Hospital, up to 6 months</time_frame>
    <description>Total in-Hospital and Intensive Care Unit stay (in days)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiopulmonary bypass time in minutes needed in the surgery</measure>
    <time_frame>day 1 after surgery</time_frame>
    <description>Cardiopulmonary bypass time in minutes needed in the surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cross-clamp ischemic heart time in minutes needed in the surgery</measure>
    <time_frame>day 1 after surgery</time_frame>
    <description>Cross-clamp ischemic heart time in minutes needed in the surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transfusional requirements (number of red packed cells, fresh frozen plasma and platelets)</measure>
    <time_frame>rom date of surgery until the date of first documented transfusional requirement assessed up to 17 years</time_frame>
    <description>transfusional needs in long term follow up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Structural valve deterioration (SVD) in bioprosthesis</measure>
    <time_frame>From date of surgery until the date of first documented SVD assessed up to 17 years</time_frame>
    <description>increase in 20 mmHg in transaortic gradient since discharge echocardiography, any aortic regurgitation greater than moderate or need for bioprosthesis reoperation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiovascular cause of rehospitalization</measure>
    <time_frame>f first documented Cardiovascular cause of rehospitalization assessed up to 17 years</time_frame>
    <description>any cardiovascular cause which need rehospitalization after surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postsurgery Mean transprosthetic gradients in mmHg</measure>
    <time_frame>From date of surgery until the date of Hospital Discharge, documented first Mean transprosthetic gradient in mmHg assessed by echocardiography after surgery.</time_frame>
    <description>measured by the first echocardiography after surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Late Mean transprosthetic gradients in mmHg</measure>
    <time_frame>From date of surgery until the date of last documented echocardiography assessed up to 17 years</time_frame>
    <description>measured by the last echocardiography in follow up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Any prosthetic infective endocarditis</measure>
    <time_frame>From date of surgery until the date of first documented prosthetic infective endocarditis, assessed up to 17 years</time_frame>
    <description>definite diagnosis of early or late infective endocarditis</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">1200</enrollment>
  <condition>Surgery</condition>
  <condition>Survival, Prosthesis</condition>
  <condition>Valve Heart Disease</condition>
  <arm_group>
    <arm_group_label>Bioprosthesis</arm_group_label>
    <description>All patients operated on of isolated AVR with a bioprosthesis implantation between 2000-2015 and age 50-65 years both inclusive.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mechanical prosthesis</arm_group_label>
    <description>All patients operated on of isolated AVR with a Mechanical prosthesis implantation between 2000-2015 and age 50-65 years both inclusive.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>bioprosthesis implantation between 2000-2015</intervention_name>
    <description>Implantation of a bioprosthesis in aortic position with cardiopulmonary bypass</description>
    <arm_group_label>Bioprosthesis</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>mechanical prosthesis implantation between 2000-2015</intervention_name>
    <description>Implantation of a mechanical prosthesis in aortic position with cardiopulmonary bypass</description>
    <arm_group_label>Mechanical prosthesis</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients aged 50-65 years who underwent isolated aortic valve replacement (AVR) for severe&#xD;
        aortic stenosis from years 2000-2015 both inclusive, with bioprosthesis or mechanical&#xD;
        prosthesis&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients aged 50-65 years who underwent isolated aortic valve replacement (AVR) for&#xD;
             severe aortic stenosis from years 2000-2015 both inclusive&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Not reported Residency change (unreachable)&#xD;
&#xD;
          -  Need of concomitant surgery&#xD;
&#xD;
          -  Reoperations&#xD;
&#xD;
          -  Infective endocarditis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>EMILIANO A RODRIGUEZ-CAULO, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>FIMABIS, HOSPITAL VIRGEN DE LA VICTORIA DE MÁLAGA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Regional Universitario de Malaga</name>
      <address>
        <city>Malaga</city>
        <state>Málaga</state>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Puerta Del Mar</name>
      <address>
        <city>Cadiz</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Reina Sofia</name>
      <address>
        <city>Cordoba</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de Las Nieves</name>
      <address>
        <city>Granada</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de La Victoria</name>
      <address>
        <city>Malaga</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen Del Rocio</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen Macarena</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>July 12, 2017</study_first_submitted>
  <study_first_submitted_qc>August 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2017</study_first_posted>
  <last_update_submitted>July 24, 2018</last_update_submitted>
  <last_update_submitted_qc>July 24, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 26, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>long-term survival</keyword>
  <keyword>bioprosthesis</keyword>
  <keyword>complications</keyword>
  <keyword>anticoagulation</keyword>
  <keyword>mechanichal prosthesis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Heart Valve Diseases</mesh_term>
    <mesh_term>Prosthesis Failure</mesh_term>
  </condition_browse>
  <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/NCT03239509
org study id: ANDALVALVE STUDY
nct id: NCT03239509
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Currently there is an increase in the use of bioprosthesis worldwide (> 70% according to
      national data of the Spanish Society of Thoracic and Cardiovascular Surgery).

      There is conflicting evidence regarding the long-term survival of patients aged 50-65 years
      with mechanical (M) or biological (B) aortic prostheses. General consensus of greater
      complications associated with the use of long-life anticoagulation in M and of reoperation in
      B.

      Similar survival with lower MACCE complications in bioprosthesis could reconsider their
      choice in patients aged 50-65 years, specially in the current TAVI era.

      The investigators are going to perform a multicentric retrospective observational study
      (Registry) about 15 year-outcomes Following Bioprosthetic vs Mechanical Isolated Aortic Valve
      Replacement for Aortic Stenosis in Patients Aged 50 to 65 Years in 5 Cardiovascular Surgery
      Centers in Andalousia (south Spain)
Objectives The main objective is to analyze long-term survival (15 years) and major
      cardiovascular complications (MACE, (death of any cause, neurological events (TIA / stroke),
      any prosthesis reoperation, and major bleeding), in patients aged 50-65 years who underwent
      isolated aortic valve replacement (AVR) due to severe aortic stenosis . Secondary objectives
      were to analyze the evolution of transprosthetic gradients by echocardiography, type of INR
      control, and degree of significant structural degeneration in bioprostheses.

      Material and Method: A retrospective analytical study of patients aged 50-65 years who
      underwent AVR surgery for stenosis between 2000-2015 in all centers with a Cardiovascular
      Surgery Dept. in Andalousia (SPAIN) as an inclusion criterion. As exclusion criteria,
      autonomic change of residence, need for concomitant surgery, previous cardiac interventions
      and endocarditis. Survival analysis and clinical data will be performed through the Diraya
      Health Care medical records (DAE), direct telephone contact with family and / or relatives, A
      crude analysis of the data and a posterior analysis by propensity score matching with the
      help of the Foundation for Biomedical Research of Malaga (IBIMA) with SPSS software will be
      carried out using a 1: 1 "nearest neighbour" matching protocol based on the Number of total
      bioprosthesis. A total sample of more than 1200 cases is expected, of which about 380 would
      be bioprostheses that would serve as a basis for the pairing. To find a 10% difference in the
      primary endpoint, two groups of 325 patients are required for a p = 0.05 and 80% for a
      bilateral contrast of two independent proportions. Sub-analysis will be performed by
      subgroups of age (50-59 vs. 60-65 years) and another according to the mark of the 2
      prostheses of each type most used. All statistical analyzes will be two-tailed with an alpha
      error of 0.05 to consider statistically significant data, and will be reviewed by IBIMA
      biostatistics.

      Conclusions: A positive result (similar survival and prosthetic durability in group B, with
      lower complications) could change the current indications of AVS in our environment, allowing
      the age of indication of bioprostheses to be reduced below 60 years.
observational model: Cohort
time perspective: Retrospective
measure: Number of participants alive
time frame: From date of surgery until the date of death from any cause, assessed up to 17 years
description: Survival since surgery
measure: Late postoperative endpoint of 4 MACE complications
time frame: From date of surgery until the date of first documented MACE (see description) or date of death from any cause, whichever came first, assessed up to 17 years
description: All cause Mortality, major bleeding, cerebrovascular or transient ischemic accident, and need of any prosthesis reintervention (Major Adverse Cardiovascular Events, MACE)
measure: Total in-Hospital and Intensive Care Unit stay (in days)
time frame: From date of surgery to discharge of the unit and Hospital, up to 6 months
description: Total in-Hospital and Intensive Care Unit stay (in days)
measure: Cardiopulmonary bypass time in minutes needed in the surgery
time frame: day 1 after surgery
description: Cardiopulmonary bypass time in minutes needed in the surgery
measure: Cross-clamp ischemic heart time in minutes needed in the surgery
time frame: day 1 after surgery
description: Cross-clamp ischemic heart time in minutes needed in the surgery
measure: Transfusional requirements (number of red packed cells, fresh frozen plasma and platelets)
time frame: rom date of surgery until the date of first documented transfusional requirement assessed up to 17 years
description: transfusional needs in long term follow up
measure: Structural valve deterioration (SVD) in bioprosthesis
time frame: From date of surgery until the date of first documented SVD assessed up to 17 years
description: increase in 20 mmHg in transaortic gradient since discharge echocardiography, any aortic regurgitation greater than moderate or need for bioprosthesis reoperation
measure: Cardiovascular cause of rehospitalization
time frame: f first documented Cardiovascular cause of rehospitalization assessed up to 17 years
description: any cardiovascular cause which need rehospitalization after surgery
measure: Postsurgery Mean transprosthetic gradients in mmHg
time frame: From date of surgery until the date of Hospital Discharge, documented first Mean transprosthetic gradient in mmHg assessed by echocardiography after surgery.
description: measured by the first echocardiography after surgery
measure: Late Mean transprosthetic gradients in mmHg
time frame: From date of surgery until the date of last documented echocardiography assessed up to 17 years
description: measured by the last echocardiography in follow up
measure: Any prosthetic infective endocarditis
time frame: From date of surgery until the date of first documented prosthetic infective endocarditis, assessed up to 17 years
description: definite diagnosis of early or late infective endocarditis
arm group label: Bioprosthesis
description: All patients operated on of isolated AVR with a bioprosthesis implantation between 2000-2015 and age 50-65 years both inclusive.
arm group label: Mechanical prosthesis
description: All patients operated on of isolated AVR with a Mechanical prosthesis implantation between 2000-2015 and age 50-65 years both inclusive.
intervention type: Procedure
intervention name: bioprosthesis implantation between 2000-2015
description: Implantation of a bioprosthesis in aortic position with cardiopulmonary bypass
arm group label: Bioprosthesis
intervention type: Procedure
intervention name: mechanical prosthesis implantation between 2000-2015
description: Implantation of a mechanical prosthesis in aortic position with cardiopulmonary bypass
arm group label: Mechanical prosthesis
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 50 Years
maximum age: 65 Years
healthy volunteers: No
last name: EMILIANO A RODRIGUEZ-CAULO, MD, PhD
role: Principal Investigator
affiliation: FIMABIS, HOSPITAL VIRGEN DE LA VICTORIA DE MÁLAGA
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Spain
responsible party type: Sponsor
mesh term: Heart Diseases
mesh term: Heart Valve Diseases
mesh term: Prosthesis Failure
sharing ipd: No