<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/NCT04496648</url>
  </required_header>
  <id_info>
    <org_study_id>H-18009651</org_study_id>
    <nct_id>NCT04496648</nct_id>
  </id_info>
  <brief_title>Percutaneous Coronary Intervention Versus Medical Treatment for Stable Angina Pectoris</brief_title>
  <acronym>DANANGINA</acronym>
  <official_title>The Danish Randomized Sham-Controlled Study of Invasive Versus Medical Treatment for Stable Angina Pectoris</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Herlev and Gentofte Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Herlev and Gentofte 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>
      Patients with ischemic heart disease and symptoms due to lack of oxygen to the heart on&#xD;
      exertion (stable angina pectoris) are usually treated by either percutaneous coronary&#xD;
      intervention (PCI) or optimal medical therapy (OMT) alone. In patients with mild to moderate&#xD;
      coronary artery disease the prognostic impact of PCI is probably limited. Furthermore it is&#xD;
      unclear which treatment is superior in terms of relieving symptoms (PCI or OMT). In this&#xD;
      trial, patients with mild to moderate coronary artery disease will be randomized to PCI or&#xD;
      sham-PCI. All patients will undergo optimal medical therapy. It is hypothesized that PCI is&#xD;
      superior to sham-PCI in patients with stable angina pectoris undergoing optimal medical&#xD;
      therapy in terms of symptom-relief.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Ischemic heart disease (IHD) is a major cause of death and disability worldwide. Patients&#xD;
      with ischemic heart disease and symptoms due to lack of oxygen to the heart on exertion&#xD;
      (stable angina pectoris) are usually treated by either percutaneous coronary intervention&#xD;
      (PCI) or optimal medical therapy (OMT) alone. In patients with mild to moderate coronary&#xD;
      artery disease the prognostic impact of PCI is probably limited. Furthermore it is unclear&#xD;
      which treatment is superior in terms of relieving symptoms (PCI or OMT). Both treatments are&#xD;
      effective in terms of reducing symptoms, but come with potential side effects.&#xD;
&#xD;
      PCI has in previous trials failed to show superiority compared to medical therapy in patients&#xD;
      with stable angina pectoris. However, many visually significant lesions do not limit the&#xD;
      blood flow significantly to the heart, and stenting such a lesion only exposes the patient to&#xD;
      the risk of side effects of intervention. In recent years it has therefore become&#xD;
      guideline-recommended practice to perform physiological test to evaluate a potential&#xD;
      stenosis. During an angiography this is most often done using fractional flow reserve (FFR).&#xD;
&#xD;
      This study tests the optimal strategy for treatment of angina-symptoms in patients with&#xD;
      stable pectoris. PCI is performed with modern stent designs and use of intravascular&#xD;
      functional testing (FFR-guided PCI) and compared to sham-PCI.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 15, 2020</start_date>
  <completion_date type="Anticipated">September 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">May 31, 2022</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>Randomized patient-blind sham-controlled trial</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Combined endpoint of strategy success</measure>
    <time_frame>3 months</time_frame>
    <description>Number of patients without angina (freedom from angina) and without hospital admission for intolerable stable angina pectoris, unstable angina pectoris, or acute myocardial infarction</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of all-cause death, any myocardial infarction, stroke, major bleeding, and severe drug reaction</measure>
    <time_frame>3 months</time_frame>
    <description>see above</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of conversions to PCI for procedural complication (sham-PCI group)</measure>
    <time_frame>3 months</time_frame>
    <description>see above</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with hospital admission for intolerable stable angina, unstable angina pectoris, or acute myocardial infarction</measure>
    <time_frame>3 months</time_frame>
    <description>see above</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients in CCS class 1, 2, and 3, respectively, without hospital admission for intolerable stable angina, unstable angina pectoris, or acute myocardial infarction</measure>
    <time_frame>3 months</time_frame>
    <description>see above</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically driven coronary revascularization</measure>
    <time_frame>3 months</time_frame>
    <description>see above</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in CCS class</measure>
    <time_frame>3 months</time_frame>
    <description>see above</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Use of antianginal agents</measure>
    <time_frame>3 months</time_frame>
    <description>0, 1, 2, or 3 agents</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life score</measure>
    <time_frame>3 months</time_frame>
    <description>5- level EQ-5D (EQ-5D-5L) questionnaire. Each dimension will be scored from 0-5 where a higher score means a better outcome. .</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in angina-specific quality of life</measure>
    <time_frame>3 months</time_frame>
    <description>Seattle Angina Questionnaire 7. Values will range from 0-100 where higher score means better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Primary composite endpoint in the modified intention-to-treat population</measure>
    <time_frame>3 months</time_frame>
    <description>The modified intention-to-treat population is comprised of patients who underwent the study procedure and follow-up without overt or formal unblinding.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in CCS class in the modified intention-to-treat population</measure>
    <time_frame>3 months</time_frame>
    <description>The modified intention-to-treat population is comprised of patients who underwent the study procedure and follow-up without overt or formal unblinding.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Seattle Angina Questionnaire 7 score in the modified intention-to-treat population</measure>
    <time_frame>3 months</time_frame>
    <description>The modified intention-to-treat population is comprised of patients who underwent the study procedure and follow-up without overt or formal unblinding. Values will range from 0-100 where higher score means better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in generic quality of life (EQ-5D-5L) in the modified intention-to-treat population</measure>
    <time_frame>3 months</time_frame>
    <description>The modified intention-to-treat population is comprised of patients who underwent the study procedure and follow-up without overt or formal unblinding. Each dimension will be scored from 0-5 where a higher score means a better outcome.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">450</enrollment>
  <condition>Coronary Heart Disease</condition>
  <condition>Stable Angina</condition>
  <condition>Ischemic Heart Disease</condition>
  <arm_group>
    <arm_group_label>Percutaneous Coronary Intervention</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Conventional PCI and optimal medical therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham-percutaneous coronary intervention</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Sham-PCI and optimal medical therapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Percutaneous Coronary Intervention</intervention_name>
    <description>Percutaneous coronary intervention with drug-eluting stents and modern techniques</description>
    <arm_group_label>Percutaneous Coronary Intervention</arm_group_label>
    <other_name>PCI</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Sham-percutaneous coronary intervention</intervention_name>
    <description>Sham-PCI procedure for at least 15 minutes that includes shifting the C-arm, reinserting the FFR-wire in the catheter and inflating the device.</description>
    <arm_group_label>Sham-percutaneous coronary intervention</arm_group_label>
    <other_name>sham-PCI</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          -  Age 18-85 years&#xD;
&#xD;
          -  Patients with stable angina pectoris undergoing elective coronary angiography&#xD;
&#xD;
          -  Canadian Cardiovascular Society (CCS) class 2 or 3&#xD;
&#xD;
          -  Informed consent&#xD;
&#xD;
          -  Lesions in one or more coronary vessels with a diameter &gt;2.5 mm with FFR-values ≤0.80,&#xD;
             and suitable for complete revascularization with PCI.&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          -  Contraindication to PCI or dual antiplatelet therapy (DAPT)&#xD;
&#xD;
          -  Use of or indication for oral anticoagulants (OAC) or novel oral anticoagulants (NOAC)&#xD;
&#xD;
          -  Use of clopidogrel&#xD;
&#xD;
          -  Life expectancy of less than 2 years&#xD;
&#xD;
          -  Severe valvular disease&#xD;
&#xD;
          -  Severe comorbidity&#xD;
&#xD;
          -  Acute coronary event within the past 12 months&#xD;
&#xD;
          -  Left ventricular ejection fraction ≤35%.&#xD;
&#xD;
          -  Renal function with estimated glomerular filtration rate (eGFR) &lt;30 mL/min&#xD;
&#xD;
          -  Pregnant or nursing&#xD;
&#xD;
          -  Severe coronary artery disease (left main stenosis, 3-vessel disease, proximal left&#xD;
             anterior descending stenosis, chronic total occlusion of major vessel)&#xD;
&#xD;
          -  Coronary disease where complete revascularization by PCI is considered difficult or&#xD;
             impossible.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ole Havndrup</last_name>
    <role>Principal Investigator</role>
    <affiliation>Zealand Unviersity Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ole Ahlehoff</last_name>
    <role>Principal Investigator</role>
    <affiliation>Odense University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ashkan Eftekhari</last_name>
    <role>Principal Investigator</role>
    <affiliation>Aarhus University Hospital Skejby</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Martin Kirk</last_name>
    <role>Principal Investigator</role>
    <affiliation>Aalborg University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rikke Sørensen</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rigshospitalet, Denmark</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sune Ammentorp Haahr-Pedersen, MD</last_name>
    <phone>+45 38672267</phone>
    <phone_ext>+4530220889</phone_ext>
    <email>sunped01@regionh.dk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Niels Thue Olsen, MD, PhD</last_name>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Gentofte University Hospital</name>
      <address>
        <city>Gentofte</city>
        <state>Copenhagen</state>
        <zip>2900</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Niels Thue Olsen, MD, PhD</last_name>
      <phone>+45 38 67 25 60</phone>
      <email>niels.thue.olsen@regionh.dk</email>
    </contact>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>June 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2020</study_first_posted>
  <last_update_submitted>July 29, 2020</last_update_submitted>
  <last_update_submitted_qc>July 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Herlev and Gentofte Hospital</investigator_affiliation>
    <investigator_full_name>Sune Ammentorp Haahr-Pedersen</investigator_full_name>
    <investigator_title>Primary Investigator</investigator_title>
  </responsible_party>
  <keyword>Atherosclerosis</keyword>
  <keyword>Fractional flow reserve</keyword>
  <keyword>Optimal medical therapy</keyword>
  <keyword>Antianginal</keyword>
  <keyword>Percutaneous Coronary Intervention</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Angina Pectoris</mesh_term>
    <mesh_term>Coronary Disease</mesh_term>
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Angina, Stable</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Data will be shared upon request.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>1 year after publication</ipd_time_frame>
    <ipd_access_criteria>Upon request</ipd_access_criteria>
  </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/NCT04496648
org study id: H-18009651
nct id: NCT04496648
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Patients with ischemic heart disease and symptoms due to lack of oxygen to the heart on
      exertion (stable angina pectoris) are usually treated by either percutaneous coronary
      intervention (PCI) or optimal medical therapy (OMT) alone. In patients with mild to moderate
      coronary artery disease the prognostic impact of PCI is probably limited. Furthermore it is
      unclear which treatment is superior in terms of relieving symptoms (PCI or OMT). In this
      trial, patients with mild to moderate coronary artery disease will be randomized to PCI or
      sham-PCI. All patients will undergo optimal medical therapy. It is hypothesized that PCI is
      superior to sham-PCI in patients with stable angina pectoris undergoing optimal medical
      therapy in terms of symptom-relief.
Ischemic heart disease (IHD) is a major cause of death and disability worldwide. Patients
      with ischemic heart disease and symptoms due to lack of oxygen to the heart on exertion
      (stable angina pectoris) are usually treated by either percutaneous coronary intervention
      (PCI) or optimal medical therapy (OMT) alone. In patients with mild to moderate coronary
      artery disease the prognostic impact of PCI is probably limited. Furthermore it is unclear
      which treatment is superior in terms of relieving symptoms (PCI or OMT). Both treatments are
      effective in terms of reducing symptoms, but come with potential side effects.

      PCI has in previous trials failed to show superiority compared to medical therapy in patients
      with stable angina pectoris. However, many visually significant lesions do not limit the
      blood flow significantly to the heart, and stenting such a lesion only exposes the patient to
      the risk of side effects of intervention. In recent years it has therefore become
      guideline-recommended practice to perform physiological test to evaluate a potential
      stenosis. During an angiography this is most often done using fractional flow reserve (FFR).

      This study tests the optimal strategy for treatment of angina-symptoms in patients with
      stable pectoris. PCI is performed with modern stent designs and use of intravascular
      functional testing (FFR-guided PCI) and compared to sham-PCI.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized patient-blind sham-controlled trial
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Combined endpoint of strategy success
time frame: 3 months
description: Number of patients without angina (freedom from angina) and without hospital admission for intolerable stable angina pectoris, unstable angina pectoris, or acute myocardial infarction
measure: Number of all-cause death, any myocardial infarction, stroke, major bleeding, and severe drug reaction
time frame: 3 months
description: see above
measure: Number of conversions to PCI for procedural complication (sham-PCI group)
time frame: 3 months
description: see above
measure: Number of patients with hospital admission for intolerable stable angina, unstable angina pectoris, or acute myocardial infarction
time frame: 3 months
description: see above
measure: Number of patients in CCS class 1, 2, and 3, respectively, without hospital admission for intolerable stable angina, unstable angina pectoris, or acute myocardial infarction
time frame: 3 months
description: see above
measure: Number of patients with clinically driven coronary revascularization
time frame: 3 months
description: see above
measure: Change in CCS class
time frame: 3 months
description: see above
measure: Use of antianginal agents
time frame: 3 months
description: 0, 1, 2, or 3 agents
measure: Quality of life score
time frame: 3 months
description: 5- level EQ-5D (EQ-5D-5L) questionnaire. Each dimension will be scored from 0-5 where a higher score means a better outcome. .
measure: Change in angina-specific quality of life
time frame: 3 months
description: Seattle Angina Questionnaire 7. Values will range from 0-100 where higher score means better outcome.
measure: Primary composite endpoint in the modified intention-to-treat population
time frame: 3 months
description: The modified intention-to-treat population is comprised of patients who underwent the study procedure and follow-up without overt or formal unblinding.
measure: Change in CCS class in the modified intention-to-treat population
time frame: 3 months
description: The modified intention-to-treat population is comprised of patients who underwent the study procedure and follow-up without overt or formal unblinding.
measure: Change in Seattle Angina Questionnaire 7 score in the modified intention-to-treat population
time frame: 3 months
description: The modified intention-to-treat population is comprised of patients who underwent the study procedure and follow-up without overt or formal unblinding. Values will range from 0-100 where higher score means better outcome.
measure: Change in generic quality of life (EQ-5D-5L) in the modified intention-to-treat population
time frame: 3 months
description: The modified intention-to-treat population is comprised of patients who underwent the study procedure and follow-up without overt or formal unblinding. Each dimension will be scored from 0-5 where a higher score means a better outcome.
arm group label: Percutaneous Coronary Intervention
arm group type: Active Comparator
description: Conventional PCI and optimal medical therapy
arm group label: Sham-percutaneous coronary intervention
arm group type: Placebo Comparator
description: Sham-PCI and optimal medical therapy
intervention type: Procedure
intervention name: Percutaneous Coronary Intervention
description: Percutaneous coronary intervention with drug-eluting stents and modern techniques
arm group label: Percutaneous Coronary Intervention
other name: PCI
intervention type: Procedure
intervention name: Sham-percutaneous coronary intervention
description: Sham-PCI procedure for at least 15 minutes that includes shifting the C-arm, reinserting the FFR-wire in the catheter and inflating the device.
arm group label: Sham-percutaneous coronary intervention
other name: sham-PCI
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Ole Havndrup
role: Principal Investigator
affiliation: Zealand Unviersity Hospital
last name: Ole Ahlehoff
role: Principal Investigator
affiliation: Odense University Hospital
last name: Ashkan Eftekhari
role: Principal Investigator
affiliation: Aarhus University Hospital Skejby
last name: Martin Kirk
role: Principal Investigator
affiliation: Aalborg University Hospital
last name: Rikke Sørensen
role: Principal Investigator
affiliation: Rigshospitalet, Denmark
last name: Sune Ammentorp Haahr-Pedersen, MD
phone: +45 38672267
phone ext: +4530220889
email: sunped01@regionh.dk
last name: Niels Thue Olsen, MD, PhD
facility: 
status: Recruiting
contact: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Herlev and Gentofte Hospital
investigator full name: Sune Ammentorp Haahr-Pedersen
investigator title: Primary Investigator
mesh term: Heart Diseases
mesh term: Angina Pectoris
mesh term: Coronary Disease
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Angina, Stable
sharing ipd: Yes
ipd description: Data will be shared upon request.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: 1 year after publication
ipd access criteria: Upon request