<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/NCT03757156</url>
  </required_header>
  <id_info>
    <org_study_id>4-2018-0910</org_study_id>
    <nct_id>NCT03757156</nct_id>
  </id_info>
  <brief_title>Aspirin Withdrawal and Clinical Outcome in Patients With Moderate to High Cardiovascular Risk But Without Cardiovascular Disease</brief_title>
  <official_title>Aspirin Withdrawal and Clinical Outcome in Patients With Moderate to High Cardiovascular Risk But Without Cardiovascular Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yonsei University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yonsei University</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>
      While the efficacy of aspirin for the secondary prevention of cardiovascular disease is&#xD;
      evident, the effect of aspirin for primary prevention is unclear. The use of aspirin reduces&#xD;
      cardiovascular mortality and myocardial infarction but increases side effects such as&#xD;
      bleeding. Therefore, the use of aspirin for primary prevention in people without&#xD;
      cardiovascular disease should be determined by individual risk and clinical benefit. The&#xD;
      European guidelines have been changed to not recommend aspirin use in people without&#xD;
      cardiovascular disease, but there are still people taking aspirin for primary prevention. The&#xD;
      purpose of this study is to investigate the effect of aspirin withdrawal on cardiovascular&#xD;
      events in patients without cardiovascular disease.&#xD;
&#xD;
      This is a single center, prospective, randomized clinical study evaluating the safety and&#xD;
      efficacy of withdrawal of aspirin among patients with moderate or high cardiovascular risk.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients taking aspirin will be randomly assigned to a group that maintains taking aspirin&#xD;
      and a group that discontinues to take aspirin by 1:1 manner. The follow-up duration is five&#xD;
      years and clinical outcomes will be investigated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">March 2019</start_date>
  <completion_date type="Anticipated">November 2024</completion_date>
  <primary_completion_date type="Anticipated">November 2024</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>Aspirin maintenance group versus aspirin interruption group</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Major adverse cardiovascular events(MACE)</measure>
    <time_frame>5 years</time_frame>
    <description>Major adverse cardiovascular events is composite endpoint. It includes cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, coronary revascularization (percutaneous coronary intervention or coronary artery bypass graft), nonfatal ischemic stroke, and transient ischemic attack.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>cardiovascular death</measure>
    <time_frame>5 years</time_frame>
    <description>Individual component of primary endpoint</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>nonfatal myocardial infarction</measure>
    <time_frame>5 years</time_frame>
    <description>Individual component of primary endpoint</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>nonfatal ischemic stroke</measure>
    <time_frame>5 years</time_frame>
    <description>Individual component of primary endpoint</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>coronary revascularization</measure>
    <time_frame>5 years</time_frame>
    <description>Individual component of primary endpoint</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>transient ischemic attack</measure>
    <time_frame>5 years</time_frame>
    <description>Individual component of primary endpoint</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bleeding</measure>
    <time_frame>5 years</time_frame>
    <description>Major bleeding is defined with International Society on Thrombosis and Haemostasis (ISTH) criteria: 1) fatal bleeding; 2)Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome; 3) bleeding causing a fall in hemoglobin level of 2 g/dL or more, or leading to transfuction of two or more units of whole blood or red cells. Bleeding that is not classified as major bleeding is minor.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">4118</enrollment>
  <condition>Healthy Participants With Moderate and High Cardiovascular Risk</condition>
  <arm_group>
    <arm_group_label>Aspirin maintenance group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>People who are taking aspirin continue to take aspirin.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aspirin withdrawal group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>People who are taking aspirin stop to taking aspirin.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Withdrawal of aspirin</intervention_name>
    <description>People who are taking aspirin stop to taking aspirin.</description>
    <arm_group_label>Aspirin withdrawal group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults aged 19-80 years old&#xD;
&#xD;
          -  Subjects who are taking for more than 12 months&#xD;
&#xD;
          -  Subjects with moderate or high cardiovascular risk based on cardiovascular risk&#xD;
             classification of 2015 Korea Society of Lipidology And Atherosclerosis guideline or&#xD;
             2004 American Heart Association guideline: 1) moderate risk: people with ≥2 major risk&#xD;
             factors, 2) high risk: people with carotid atherosclerosis, abdominal aortic aneurysm,&#xD;
             or diabetes, who is taking statin&#xD;
&#xD;
          -  Subjects who voluntarily participate in the study and sign informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with a history of major cardiovascular disease confirmed by medical history&#xD;
             and medical history; myocardial infarction, angina pectoris, coronary angioplasty,&#xD;
             coronary artery bypass surgery, peripheral vascular disease, ischemic stroke,&#xD;
             transient ischemic attack&#xD;
&#xD;
          -  Subjects has any contraindication to use of aspirin or hypersensitivity to aspirin&#xD;
&#xD;
          -  Subjects with atrial fibrillation&#xD;
&#xD;
          -  Subjects who are taking anti-platelet agents other than aspirin or anticoagulants&#xD;
&#xD;
          -  Subjects who have been diagnosed with cancer within the last 5 years&#xD;
&#xD;
          -  Pregnant women or those who have pregnancy plan after enrolling in this study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Division of Cardiology, Cardiovascular Center, Severance Hospital, Yonsei University College of Medicine</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <contact>
      <last_name>Sang-Hak Lee, MD</last_name>
      <phone>82-2-2228-8460</phone>
      <email>SHL1106@yuhs.ac</email>
    </contact>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <reference>
    <citation>Antithrombotic Trialists' (ATT) Collaboration; Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, Buring J, Hennekens C, Kearney P, Meade T, Patrono C, Roncaglioni MC, Zanchetti A. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009 May 30;373(9678):1849-60. doi: 10.1016/S0140-6736(09)60503-1.</citation>
    <PMID>19482214</PMID>
  </reference>
  <reference>
    <citation>Bibbins-Domingo K; U.S. Preventive Services Task Force. Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2016 Jun 21;164(12):836-45. doi: 10.7326/M16-0577. Epub 2016 Apr 12.</citation>
    <PMID>27064677</PMID>
  </reference>
  <reference>
    <citation>Saito Y, Okada S, Ogawa H, Soejima H, Sakuma M, Nakayama M, Doi N, Jinnouchi H, Waki M, Masuda I, Morimoto T; JPAD Trial Investigators. Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus: 10-Year Follow-Up of a Randomized Controlled Trial. Circulation. 2017 Feb 14;135(7):659-670. doi: 10.1161/CIRCULATIONAHA.116.025760. Epub 2016 Nov 15.</citation>
    <PMID>27881565</PMID>
  </reference>
  <reference>
    <citation>Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, Cooney MT, Corra U, Cosyns B, Deaton C, Graham I, Hall MS, Hobbs FDR, Lochen ML, Lollgen H, Marques-Vidal P, Perk J, Prescott E, Redon J, Richter DJ, Sattar N, Smulders Y, Tiberi M, van der Worp HB, van Dis I, Verschuren WMM, Binno S; ESC Scientific Document Group. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention &amp; Rehabilitation (EACPR). Eur Heart J. 2016 Aug 1;37(29):2315-2381. doi: 10.1093/eurheartj/ehw106. Epub 2016 May 23. No abstract available.</citation>
    <PMID>27222591</PMID>
  </reference>
  <reference>
    <citation>Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998 May 12;97(18):1837-47. doi: 10.1161/01.cir.97.18.1837.</citation>
    <PMID>9603539</PMID>
  </reference>
  <reference>
    <citation>National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002 Dec 17;106(25):3143-421. No abstract available.</citation>
    <PMID>12485966</PMID>
  </reference>
  <reference>
    <citation>Ikeda Y, Shimada K, Teramoto T, Uchiyama S, Yamazaki T, Oikawa S, Sugawara M, Ando K, Murata M, Yokoyama K, Ishizuka N. Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: a randomized clinical trial. JAMA. 2014 Dec 17;312(23):2510-20. doi: 10.1001/jama.2014.15690.</citation>
    <PMID>25401325</PMID>
  </reference>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>November 23, 2018</study_first_submitted>
  <study_first_submitted_qc>November 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <last_update_submitted>February 7, 2019</last_update_submitted>
  <last_update_submitted_qc>February 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 11, 2019</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>Cardiovascular Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
  </intervention_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/NCT03757156
org study id: 4-2018-0910
nct id: NCT03757156
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
While the efficacy of aspirin for the secondary prevention of cardiovascular disease is
      evident, the effect of aspirin for primary prevention is unclear. The use of aspirin reduces
      cardiovascular mortality and myocardial infarction but increases side effects such as
      bleeding. Therefore, the use of aspirin for primary prevention in people without
      cardiovascular disease should be determined by individual risk and clinical benefit. The
      European guidelines have been changed to not recommend aspirin use in people without
      cardiovascular disease, but there are still people taking aspirin for primary prevention. The
      purpose of this study is to investigate the effect of aspirin withdrawal on cardiovascular
      events in patients without cardiovascular disease.

      This is a single center, prospective, randomized clinical study evaluating the safety and
      efficacy of withdrawal of aspirin among patients with moderate or high cardiovascular risk.
Patients taking aspirin will be randomly assigned to a group that maintains taking aspirin
      and a group that discontinues to take aspirin by 1:1 manner. The follow-up duration is five
      years and clinical outcomes will be investigated.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Aspirin maintenance group versus aspirin interruption group
primary purpose: Prevention
masking: None (Open Label)
measure: Major adverse cardiovascular events(MACE)
time frame: 5 years
description: Major adverse cardiovascular events is composite endpoint. It includes cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, coronary revascularization (percutaneous coronary intervention or coronary artery bypass graft), nonfatal ischemic stroke, and transient ischemic attack.
measure: cardiovascular death
time frame: 5 years
description: Individual component of primary endpoint
measure: nonfatal myocardial infarction
time frame: 5 years
description: Individual component of primary endpoint
measure: nonfatal ischemic stroke
time frame: 5 years
description: Individual component of primary endpoint
measure: coronary revascularization
time frame: 5 years
description: Individual component of primary endpoint
measure: transient ischemic attack
time frame: 5 years
description: Individual component of primary endpoint
measure: Bleeding
time frame: 5 years
description: Major bleeding is defined with International Society on Thrombosis and Haemostasis (ISTH) criteria: 1) fatal bleeding; 2)Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome; 3) bleeding causing a fall in hemoglobin level of 2 g/dL or more, or leading to transfuction of two or more units of whole blood or red cells. Bleeding that is not classified as major bleeding is minor.
arm group label: Aspirin maintenance group
arm group type: No Intervention
description: People who are taking aspirin continue to take aspirin.
arm group label: Aspirin withdrawal group
arm group type: Experimental
description: People who are taking aspirin stop to taking aspirin.
intervention type: Other
intervention name: Withdrawal of aspirin
description: People who are taking aspirin stop to taking aspirin.
arm group label: Aspirin withdrawal group
criteria: 
gender: All
minimum age: 19 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
contact: 
country: Korea, Republic of
citation: Antithrombotic Trialists' (ATT) Collaboration; Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, Buring J, Hennekens C, Kearney P, Meade T, Patrono C, Roncaglioni MC, Zanchetti A. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009 May 30;373(9678):1849-60. doi: 10.1016/S0140-6736(09)60503-1.
PMID: 19482214
citation: Bibbins-Domingo K; U.S. Preventive Services Task Force. Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2016 Jun 21;164(12):836-45. doi: 10.7326/M16-0577. Epub 2016 Apr 12.
PMID: 27064677
citation: Saito Y, Okada S, Ogawa H, Soejima H, Sakuma M, Nakayama M, Doi N, Jinnouchi H, Waki M, Masuda I, Morimoto T; JPAD Trial Investigators. Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus: 10-Year Follow-Up of a Randomized Controlled Trial. Circulation. 2017 Feb 14;135(7):659-670. doi: 10.1161/CIRCULATIONAHA.116.025760. Epub 2016 Nov 15.
PMID: 27881565
citation: Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, Cooney MT, Corra U, Cosyns B, Deaton C, Graham I, Hall MS, Hobbs FDR, Lochen ML, Lollgen H, Marques-Vidal P, Perk J, Prescott E, Redon J, Richter DJ, Sattar N, Smulders Y, Tiberi M, van der Worp HB, van Dis I, Verschuren WMM, Binno S; ESC Scientific Document Group. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016 Aug 1;37(29):2315-2381. doi: 10.1093/eurheartj/ehw106. Epub 2016 May 23. No abstract available.
PMID: 27222591
citation: Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998 May 12;97(18):1837-47. doi: 10.1161/01.cir.97.18.1837.
PMID: 9603539
citation: National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002 Dec 17;106(25):3143-421. No abstract available.
PMID: 12485966
citation: Ikeda Y, Shimada K, Teramoto T, Uchiyama S, Yamazaki T, Oikawa S, Sugawara M, Ando K, Murata M, Yokoyama K, Ishizuka N. Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: a randomized clinical trial. JAMA. 2014 Dec 17;312(23):2510-20. doi: 10.1001/jama.2014.15690.
PMID: 25401325
responsible party type: Sponsor
mesh term: Cardiovascular Diseases
mesh term: Aspirin
sharing ipd: No