<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/NCT04426084</url>
  </required_header>
  <id_info>
    <org_study_id>4</org_study_id>
    <nct_id>NCT04426084</nct_id>
  </id_info>
  <brief_title>Cardiovascular Risk Factors and Severe COVID-19. A Nationwide Registry-based Case-Control Study</brief_title>
  <official_title>Cardiovascular Disease, Cardiovascular Risk Factors, Treatments and Severe COVID-19 Outcomes. A Nationwide Registry-based Case-Control Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Karolinska Institutet</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Karolinska Institutet</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>
      In this study we cross-reference several nationwide high-quality Swedish registers in order&#xD;
      to study risk factors for severe Covid-19 outcomes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this nationwide, case-control study we cross-reference several detailed, high-quality&#xD;
      Swedish registers in order to study risk factors associated with severe Covid-19 as well as&#xD;
      different disease outcomes, with a focus on cardiovascular disease, chronic kidney disease,&#xD;
      different treatments and socioeconomic factors. Cases are identified through the Swedish&#xD;
      intensive care register (SIR) and controls through the Swedish population register (RTB).&#xD;
      Further information on the study participants is gathered by linkage to registers on:&#xD;
      prescribed drugs; history of in- and outpatient care; income, education and migration.&#xD;
      Follow-up data such as future hospitalization and mortality will be gathered prospectively.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 1, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Actual">June 8, 2021</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Other</time_perspective>
  </study_design_info>
  <target_duration>3 Years</target_duration>
  <primary_outcome>
    <measure>Severe Covid-19</measure>
    <time_frame>2020-03-01 to 2020-05-11</time_frame>
    <description>Admitted to ICU in Sweden with a main diagnosis of Covid-19 confirmed by laboratory testing (ICD 10: U07.1) and requring mechanical ventilation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Severe Covid-19 with pulmonary embolism</measure>
    <time_frame>2020-03-01 to 2020-05-11</time_frame>
    <description>Admitted to ICU in Sweden with a diagnosis of Covid-19 confirmed by laboratory testing (ICD 10: U07.1) and a bidiagnosis of pulmonary embolism (ICD10:I26)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>CRRT(Continuous Renal Replacement Therapy)</measure>
    <time_frame>2020-03-01 to 2020-05-11</time_frame>
    <description>Number of participants admitted to ICU in Sweden with a verified diagnosis of Covid-19 requring CRRT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ECMO (Extracorporeal Membrane Oxygenation )</measure>
    <time_frame>2020-03-01 to 2020-05-11</time_frame>
    <description>Number of participants admitted to ICU in Sweden with a verified diagnosis of Covid-19 requring ECMO</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU Mortality</measure>
    <time_frame>2020-03-01 to 2020-05-11</time_frame>
    <description>Number of participants admitted to ICU in Sweden with a verified diagnosis of Covid-19 with death occurring in ICU after admission</description>
  </secondary_outcome>
  <enrollment type="Actual">22784</enrollment>
  <condition>COVID-19</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Hypertension</intervention_name>
    <description>Exposure : Any registered diagnosis of I10 within 15 years or a registered pick-up of a prescription of antihypertensive treatment (ATC C02CA, C02DB02, C03, C07, C08, C09) within one year before index date in the Swedish prescribed drug register (exluding those with a registered diagnosis of other indications for betablocker (heart failure, atrial fibrillation) or ACE-inhibitor, ARB(heart failure) ) Exposures will be compared between cases and controls and between cases with different outcomes and controls</description>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Diabetes type 2</intervention_name>
    <description>Exposure: Any registered diagnosis of E11 within 15 years or a registered pick-up of a prescription with any antidiabetic treatment (ATC A10) within one year before index date in the Swedish prescribed drug register.&#xD;
Exposures will be compared between cases and controls and between cases with different outcomes and controls</description>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Obesity</intervention_name>
    <description>Exposure: Diagnosis ICD E66 within 15 years before index date Exposures will be compared between cases and controls and between cases with different outcomes and controls</description>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Antihypertensive Agents</intervention_name>
    <description>Pick up of a prescription of C02CA, C02DB02, C03, C07, C08, C09 registered in the Swedish prescribed drug register within 6 month before index date.&#xD;
Exposures will be studied separately for each antihypertensive class and compared between cases and controls and between cases with different outcomes and controls</description>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Statins (Cardiovascular Agents)</intervention_name>
    <description>Pick up of a prescription of C10AA registered in the Swedish prescribed drug register within 6 month before index date.</description>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Chronic kidney disease</intervention_name>
    <description>Exposure: Diagnosis ICD N18 within 15 years before index date Exposures will be compared between cases and controls and between cases with different outcomes (mechanical ventilation, continuous renal replacement therapy mortality) and controls. Exposures will thereafter be compared in subgroups by BMI at ICU-admission and in subgroups matched by history of type 2 diabetes.</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        A total of 1,424 cases and 14,240 control subjects (first analysis june 2020) A total of&#xD;
        4684 cases and 46840 control subjects (july 2022)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Cases: Admitted to intensive care unit in Sweden and registered admission in the&#xD;
             Swedish intensive care register (SIR) with a main diagnosis of Covid-19 confirmed by&#xD;
             laboratory testing (ICD10: U07.1). (cases)&#xD;
&#xD;
          -  Control subjects matched for age, gender,residency: For each case 10 controls matched&#xD;
             for age, gender and district of residence will be identified by Statistics Sweden&#xD;
             (SCB) in the Swedish population register (RTB).&#xD;
&#xD;
          -  Control subjects matched for age and gender: For each case 5 controls matched for age&#xD;
             and gender will be identified by by Statistics Sweden (SCB) in the Swedish population&#xD;
             register (RTB).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No valid Swedish personal identity number (PIN)&#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>Södersjukhuset</name>
      <address>
        <city>Stockholm</city>
        <zip>11883</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>June 9, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>July 27, 2022</last_update_submitted>
  <last_update_submitted_qc>July 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Karolinska Institutet</investigator_affiliation>
    <investigator_full_name>Per Svensson</investigator_full_name>
    <investigator_title>Associate professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antihypertensive Agents</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04426084
org study id: 4
nct id: NCT04426084
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In this study we cross-reference several nationwide high-quality Swedish registers in order
      to study risk factors for severe Covid-19 outcomes.
In this nationwide, case-control study we cross-reference several detailed, high-quality
      Swedish registers in order to study risk factors associated with severe Covid-19 as well as
      different disease outcomes, with a focus on cardiovascular disease, chronic kidney disease,
      different treatments and socioeconomic factors. Cases are identified through the Swedish
      intensive care register (SIR) and controls through the Swedish population register (RTB).
      Further information on the study participants is gathered by linkage to registers on:
      prescribed drugs; history of in- and outpatient care; income, education and migration.
      Follow-up data such as future hospitalization and mortality will be gathered prospectively.
observational model: Case-Control
time perspective: Other
measure: Severe Covid-19
time frame: 2020-03-01 to 2020-05-11
description: Admitted to ICU in Sweden with a main diagnosis of Covid-19 confirmed by laboratory testing (ICD 10: U07.1) and requring mechanical ventilation
measure: Severe Covid-19 with pulmonary embolism
time frame: 2020-03-01 to 2020-05-11
description: Admitted to ICU in Sweden with a diagnosis of Covid-19 confirmed by laboratory testing (ICD 10: U07.1) and a bidiagnosis of pulmonary embolism (ICD10:I26)
measure: CRRT(Continuous Renal Replacement Therapy)
time frame: 2020-03-01 to 2020-05-11
description: Number of participants admitted to ICU in Sweden with a verified diagnosis of Covid-19 requring CRRT
measure: ECMO (Extracorporeal Membrane Oxygenation )
time frame: 2020-03-01 to 2020-05-11
description: Number of participants admitted to ICU in Sweden with a verified diagnosis of Covid-19 requring ECMO
measure: ICU Mortality
time frame: 2020-03-01 to 2020-05-11
description: Number of participants admitted to ICU in Sweden with a verified diagnosis of Covid-19 with death occurring in ICU after admission
intervention type: Other
intervention name: Hypertension
description: Exposure : Any registered diagnosis of I10 within 15 years or a registered pick-up of a prescription of antihypertensive treatment (ATC C02CA, C02DB02, C03, C07, C08, C09) within one year before index date in the Swedish prescribed drug register (exluding those with a registered diagnosis of other indications for betablocker (heart failure, atrial fibrillation) or ACE-inhibitor, ARB(heart failure) ) Exposures will be compared between cases and controls and between cases with different outcomes and controls
intervention type: Other
intervention name: Diabetes type 2
description: Exposure: Any registered diagnosis of E11 within 15 years or a registered pick-up of a prescription with any antidiabetic treatment (ATC A10) within one year before index date in the Swedish prescribed drug register.
Exposures will be compared between cases and controls and between cases with different outcomes and controls
intervention type: Other
intervention name: Obesity
description: Exposure: Diagnosis ICD E66 within 15 years before index date Exposures will be compared between cases and controls and between cases with different outcomes and controls
intervention type: Drug
intervention name: Antihypertensive Agents
description: Pick up of a prescription of C02CA, C02DB02, C03, C07, C08, C09 registered in the Swedish prescribed drug register within 6 month before index date.
Exposures will be studied separately for each antihypertensive class and compared between cases and controls and between cases with different outcomes and controls
intervention type: Drug
intervention name: Statins (Cardiovascular Agents)
description: Pick up of a prescription of C10AA registered in the Swedish prescribed drug register within 6 month before index date.
intervention type: Other
intervention name: Chronic kidney disease
description: Exposure: Diagnosis ICD N18 within 15 years before index date Exposures will be compared between cases and controls and between cases with different outcomes (mechanical ventilation, continuous renal replacement therapy mortality) and controls. Exposures will thereafter be compared in subgroups by BMI at ICU-admission and in subgroups matched by history of type 2 diabetes.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Sweden
responsible party type: Principal Investigator
investigator affiliation: Karolinska Institutet
investigator full name: Per Svensson
investigator title: Associate professor
mesh term: COVID-19
mesh term: Antihypertensive Agents