<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/NCT04408326</url>
  </required_header>
  <id_info>
    <org_study_id>283005</org_study_id>
    <nct_id>NCT04408326</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Angiotensin II Use in Coronavirus Disease(COVID)-19 Patients With Acute Respiratory Distress Syndrome</brief_title>
  <acronym>ACES</acronym>
  <official_title>Efficacy and Safety of Angiotensin II Use in COVID-19 Patients With Acute Respiratory Distress Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Guy's and St Thomas' NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Australian and New Zealand Intensive Care Research Centre</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Monash University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Royal Surrey County Hospital NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Guy's and St Thomas' NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to find out whether the use of angiotensin II, which is a drug to raise blood&#xD;
      pressure has been approved by European Medical Agency in August 2019, as an add-on medication&#xD;
      to increase blood pressure in patients with COVID-19, acute severe lung injury, inflammation&#xD;
      and severe shock, compared with standard medication. In addition, the investigators will&#xD;
      collect the data of Anakinra, another drug which is frequently used in this condition to&#xD;
      reduce inflammation.&#xD;
&#xD;
      The investigators will collect clinical data and outcomes from critical care patients. The&#xD;
      investigators will analyse for whom these drugs are most beneficial and explore whether there&#xD;
      are any patients who don't benefit or have side effects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      COVID-19 is a rapidly evolving pandemic with approximately 5% of all patients requiring&#xD;
      admission to the intensive care unit. In critically ill patients infected with COVID-19, ARDS&#xD;
      is found in 40%, more than 25% require continuous renal replacement therapy, and more than&#xD;
      10% develop vasodilatory shock. Currently, supportive treatment is the mainstay treatment,&#xD;
      with fluid administration and vasopressors for haemodynamic support and lung-protective&#xD;
      ventilation in patients with severe respiratory failure. Targeted drugs, antiviral therapies,&#xD;
      and vaccines are still currently being developed and studied. To date, there is insufficient&#xD;
      evidence to recommend any drug over another.&#xD;
&#xD;
      Angiotensin II is a major product of the renin-angiotensin-aldosterone system (RAAS) system.&#xD;
      Initially, renin is secreted by hypotension, activation of sympathetic nervous system, and&#xD;
      decreased sodium delivery to distal tubules. Renin then stimulates angiotensinogen to be&#xD;
      converted into angiotensin I. Angiotensin I is cleaved to angiotensin II by&#xD;
      angiotensin-converting enzyme (ACE). ACE is an endothelium-bound ectoenzyme produced by&#xD;
      pulmonary endothelium and endothelium from the systemic circulation.&#xD;
&#xD;
      Angiotensin II has a variety of effects, mainly blood pressure elevation via AT-1 receptors,&#xD;
      thereby causing direct vasoconstriction, stimulation of vasopressin release for water&#xD;
      reabsorption, and stimulation of aldosterone release from the adrenal glands. Angiotensin II&#xD;
      is converted to angiotensin(1-7) by angiotensin-converting enzyme 2 (ACE2_. Angiotensin(1-7)&#xD;
      has vasodilatory, anti-inflammatory, and anti-apoptotic properties.&#xD;
&#xD;
      The RAAS system may be over- or under-stimulated during sepsis. Diseases that involve&#xD;
      pulmonary vasculature e.g. acute respiratory distress syndrome (ARDS) or endotoxaemia can&#xD;
      alter ACE function. Studies have shown that patients with lower Ang II and ACE levels were&#xD;
      more likely to die. In addition, AT-1 receptors are downregulated from increased inflammatory&#xD;
      cytokines, hence diminished vasopressor response in sepsis patients. In COVID-19 patients&#xD;
      with ARDS, four mechanisms are proposed in response to deficient functional ACE. First,&#xD;
      inadequate production of angiotensin II leads to decreased AT-1 receptor activation, leading&#xD;
      to vasodilatation and hypotension. Second, the accumulation of its substrate, angiotensin I,&#xD;
      leads to catabolism of angiotensin I into angiotensin(1-7), which causes further&#xD;
      vasodilatation. Third, angiotensin(1-7) activates nitric oxide(NO) synthase, stimulates&#xD;
      production of NO, another potent vasodilator. Lastly, dysfunctional ACE impairs ACE-dependent&#xD;
      hydrolysis of bradykinin, which is another vasodilatory substance. Furthermore, COVID-19 has&#xD;
      been shown to bind to the ACE2 receptor for cell entry and viral replication. Angiotensin II&#xD;
      has been shown in vitro to downregulate ACE2 by internalization and degradation in both mouse&#xD;
      and human models.&#xD;
&#xD;
      Therefore, exogenous angiotensin II is proposed as a potent vasoconstrictor in&#xD;
      COVID-19-associated ARDS with vasodilatory shock. Several studies, including a recent&#xD;
      randomised controlled trial, have shown angiotensin II as an effective vasopressor. In the&#xD;
      largest trial to date, 321 patients were randomized to Ang II (n=163) or placebo (n=158).&#xD;
      Most of the included patients had sepsis (80.7%). Patients were included if they were more&#xD;
      than 18 years old with vasodilatory shock, defined as mean arterial pressure (MAP) between 55&#xD;
      and 70 mmHg, requiring norepinephrine equivalent dose ≥ 0.2 mcg/kg/min for at least 6 hours,&#xD;
      had received at least 25 mL/kg crystalloids within the last 24 hours, and met either of the&#xD;
      following criteria; cardiac index more than 2.3 L/min, central venous oxygen saturation&#xD;
      (ScvO2) &gt; 70%, or central venous pressure (CVP) &gt; 8 mmHg. Patients who were randomized to Ang&#xD;
      II had a higher proportion of meeting MAP target of ≥ 75 mmHg or a ≥ 10 mmHg increase in MAP&#xD;
      at 3 hours compared with placebo (69.9% vs 23.4%; p &lt;0.001). Patients who received&#xD;
      angiotensin II also had lower noradrenaline requirement at 3 hours and lower cardiovascular&#xD;
      SOFA score at 48 hours. Subsequent post-hoc analyses have shown that patients who received&#xD;
      Angiotensin II were more likely to be liberated from renal replacement therapy (RRT) within 7&#xD;
      days (38% Ang II versus 15% placebo; p = 0.007). Those who might benefit from Ang II included&#xD;
      patients with acute physiologic and chronic health evaluation (APACHE) II score ≥ 30, those&#xD;
      with elevated renin and lower baseline Ang II levels, and severe ARDS patients with partial&#xD;
      pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio &lt; 100. In 2019, the&#xD;
      European Medical Agency approved angiotensin II as a vasoconstrictor to raise blood pressure&#xD;
      in patients with septic or other distributive shock who remain hypotensive despite adequate&#xD;
      volume restitution and application of catecholamines and other available vasopressor&#xD;
      therapies.&#xD;
&#xD;
      Noradrenaline is currently recommended by the consensus guideline as the first line&#xD;
      vasopressor for COVID-19 patients with vasodilatory shock. There is insufficient evidence to&#xD;
      issue a treatment recommendation on the use of angiotensin II in critically ill adults with&#xD;
      confirmed COVID-19 infection with ARDS and vasodilatory shock. Therefore, this study aims to&#xD;
      compare the efficacy of angiotensin II as an add-on vasopressor with optimised standard of&#xD;
      care.&#xD;
&#xD;
      Critically ill patients with COVID-19 infection also often receive Anakinra to modulate the&#xD;
      inflammatory response. The investigators would also like to collect the data of patients&#xD;
      treated with and without Anakinra.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 1, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Proportions of patients with mean arterial pressure ≥ 65 mmHg or an increase of mean arterial pressure ≥10 mmHg at 3 hours</measure>
    <time_frame>3 hours</time_frame>
    <description>Percentage</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Noradrenaline dose</measure>
    <time_frame>1 hour and 3 hours</time_frame>
    <description>microgram/kg/min</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sequential Organ Failure Assessment (SOFA) score</measure>
    <time_frame>baseline, 24, and 48 hours</time_frame>
    <description>Changes in score, minimum 0, maximum 24, the higher score showing worse prognosis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RRT-free days</measure>
    <time_frame>28 days</time_frame>
    <description>Patients who are alive and do not require renal replacement therapy at 28 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RRT discontinuation</measure>
    <time_frame>7 and 28 days</time_frame>
    <description>Proportions of patients who do not require renal replacement therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum creatinine</measure>
    <time_frame>7 days and 28 days</time_frame>
    <description>micromol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PaO2/FiO2 ratio</measure>
    <time_frame>baseline, 24, and 48 hours</time_frame>
    <description>Changes in value</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>7 days and 28 days</time_frame>
    <description>Mortality rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>28 days</time_frame>
    <description>e.g. arrhythmia, thromboembolism, etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in serum C-reactive protein</measure>
    <time_frame>7 days</time_frame>
    <description>Change in serum C-reactive protein</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in serum ferritin</measure>
    <time_frame>7 days</time_frame>
    <description>Change in serum ferritin</description>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Anticipated">50</enrollment>
  <condition>COVID</condition>
  <condition>Acute Respiratory Distress Syndrome</condition>
  <arm_group>
    <arm_group_label>Angiotensin II</arm_group_label>
    <description>Patients with COVID-19 and acute respiratory distress syndrome who received angiotensin II as an add-on vasopressor will be collected</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anakinra</arm_group_label>
    <description>Patients with COVID-19 and acute respiratory distress syndrome who received Anakinra (interleukin 1 receptor antagonist) will be collected</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Angiotensin II control</arm_group_label>
    <description>Patients with COVID-19 and acute respiratory distress syndrome who also received vasopressor support will be matched to angiotensin II group by date of intensive care unit admission, age, history of hypertension, history of angiotensin converting enzyme inhibitor/angiotensin receptor blocker, respiratory support</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anakinra control</arm_group_label>
    <description>Patients with COVID-19 and acute respiratory distress syndrome will be matched to Anakinra group by matching age and date of intensive unit care admission</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Angiotensin II</intervention_name>
    <description>Exogenous angiotensin II acts on angiotensin II type 1 receptor and raise blood pressure by vasoconstriction, salt and water retention, and stimulation of aldosterone hormone</description>
    <arm_group_label>Angiotensin II</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Interleukin-1 receptor antagonist</intervention_name>
    <description>Interleukin-1 receptor antagonist is an immunomodulating drug aiming to mitigate cytokine storm in COVID-19 patients</description>
    <arm_group_label>Anakinra</arm_group_label>
    <other_name>Anakinra</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Adult patients with confirmed COVID-19 infection and acute respiratory distress syndrome&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult patients (≥ 18 years old) admitted to intensive care units overseen by critical&#xD;
             care consultants&#xD;
&#xD;
          2. Confirmed COVID-19 infection&#xD;
&#xD;
          3. ARDS defined as per the BERLIN ARDS definition1&#xD;
&#xD;
          4. For angiotensin data only: Vasodilatory shock as diagnosed clinically by the treating&#xD;
             physicians and receiving noradrenaline for less than 12 hours from the onset of shock&#xD;
             or arrival to hospital&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pure cardiogenic shock&#xD;
&#xD;
          2. Stage 4 cancer&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marlies Ostermann</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Critical Care, Guy's &amp; St Thomas' Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Marlies Ostermann, MD, PhD</last_name>
    <phone>0044 207 188 3038</phone>
    <email>Marlies.Ostermann@gstt.nhs.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Nuttha Lumlertgul, MD, PhD</last_name>
    <phone>0044 207 188 3038</phone>
    <email>Nuttha.Lumlertgul@gstt.nhs.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Guy's &amp; St Thomas' Hospital</name>
      <address>
        <city>London</city>
        <zip>SE1 7EH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marlies Ostermann, MD, PhD</last_name>
      <phone>020 71883038</phone>
      <email>Marlies.Ostermann@gstt.nhs.uk</email>
    </contact>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>May 27, 2020</study_first_submitted>
  <study_first_submitted_qc>May 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>August 3, 2021</last_update_submitted>
  <last_update_submitted_qc>August 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 4, 2021</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>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Interleukin 1 Receptor Antagonist Protein</mesh_term>
    <mesh_term>Angiotensin II</mesh_term>
    <mesh_term>Giapreza</mesh_term>
    <mesh_term>Angiotensinogen</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04408326
org study id: 283005
nct id: NCT04408326
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This study aims to find out whether the use of angiotensin II, which is a drug to raise blood
      pressure has been approved by European Medical Agency in August 2019, as an add-on medication
      to increase blood pressure in patients with COVID-19, acute severe lung injury, inflammation
      and severe shock, compared with standard medication. In addition, the investigators will
      collect the data of Anakinra, another drug which is frequently used in this condition to
      reduce inflammation.

      The investigators will collect clinical data and outcomes from critical care patients. The
      investigators will analyse for whom these drugs are most beneficial and explore whether there
      are any patients who don't benefit or have side effects.
COVID-19 is a rapidly evolving pandemic with approximately 5% of all patients requiring
      admission to the intensive care unit. In critically ill patients infected with COVID-19, ARDS
      is found in 40%, more than 25% require continuous renal replacement therapy, and more than
      10% develop vasodilatory shock. Currently, supportive treatment is the mainstay treatment,
      with fluid administration and vasopressors for haemodynamic support and lung-protective
      ventilation in patients with severe respiratory failure. Targeted drugs, antiviral therapies,
      and vaccines are still currently being developed and studied. To date, there is insufficient
      evidence to recommend any drug over another.

      Angiotensin II is a major product of the renin-angiotensin-aldosterone system (RAAS) system.
      Initially, renin is secreted by hypotension, activation of sympathetic nervous system, and
      decreased sodium delivery to distal tubules. Renin then stimulates angiotensinogen to be
      converted into angiotensin I. Angiotensin I is cleaved to angiotensin II by
      angiotensin-converting enzyme (ACE). ACE is an endothelium-bound ectoenzyme produced by
      pulmonary endothelium and endothelium from the systemic circulation.

      Angiotensin II has a variety of effects, mainly blood pressure elevation via AT-1 receptors,
      thereby causing direct vasoconstriction, stimulation of vasopressin release for water
      reabsorption, and stimulation of aldosterone release from the adrenal glands. Angiotensin II
      is converted to angiotensin(1-7) by angiotensin-converting enzyme 2 (ACE2_. Angiotensin(1-7)
      has vasodilatory, anti-inflammatory, and anti-apoptotic properties.

      The RAAS system may be over- or under-stimulated during sepsis. Diseases that involve
      pulmonary vasculature e.g. acute respiratory distress syndrome (ARDS) or endotoxaemia can
      alter ACE function. Studies have shown that patients with lower Ang II and ACE levels were
      more likely to die. In addition, AT-1 receptors are downregulated from increased inflammatory
      cytokines, hence diminished vasopressor response in sepsis patients. In COVID-19 patients
      with ARDS, four mechanisms are proposed in response to deficient functional ACE. First,
      inadequate production of angiotensin II leads to decreased AT-1 receptor activation, leading
      to vasodilatation and hypotension. Second, the accumulation of its substrate, angiotensin I,
      leads to catabolism of angiotensin I into angiotensin(1-7), which causes further
      vasodilatation. Third, angiotensin(1-7) activates nitric oxide(NO) synthase, stimulates
      production of NO, another potent vasodilator. Lastly, dysfunctional ACE impairs ACE-dependent
      hydrolysis of bradykinin, which is another vasodilatory substance. Furthermore, COVID-19 has
      been shown to bind to the ACE2 receptor for cell entry and viral replication. Angiotensin II
      has been shown in vitro to downregulate ACE2 by internalization and degradation in both mouse
      and human models.

      Therefore, exogenous angiotensin II is proposed as a potent vasoconstrictor in
      COVID-19-associated ARDS with vasodilatory shock. Several studies, including a recent
      randomised controlled trial, have shown angiotensin II as an effective vasopressor. In the
      largest trial to date, 321 patients were randomized to Ang II (n=163) or placebo (n=158).
      Most of the included patients had sepsis (80.7%). Patients were included if they were more
      than 18 years old with vasodilatory shock, defined as mean arterial pressure (MAP) between 55
      and 70 mmHg, requiring norepinephrine equivalent dose ≥ 0.2 mcg/kg/min for at least 6 hours,
      had received at least 25 mL/kg crystalloids within the last 24 hours, and met either of the
      following criteria; cardiac index more than 2.3 L/min, central venous oxygen saturation
      (ScvO2) > 70%, or central venous pressure (CVP) > 8 mmHg. Patients who were randomized to Ang
      II had a higher proportion of meeting MAP target of ≥ 75 mmHg or a ≥ 10 mmHg increase in MAP
      at 3 hours compared with placebo (69.9% vs 23.4%; p <0.001). Patients who received
      angiotensin II also had lower noradrenaline requirement at 3 hours and lower cardiovascular
      SOFA score at 48 hours. Subsequent post-hoc analyses have shown that patients who received
      Angiotensin II were more likely to be liberated from renal replacement therapy (RRT) within 7
      days (38% Ang II versus 15% placebo; p = 0.007). Those who might benefit from Ang II included
      patients with acute physiologic and chronic health evaluation (APACHE) II score ≥ 30, those
      with elevated renin and lower baseline Ang II levels, and severe ARDS patients with partial
      pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio < 100. In 2019, the
      European Medical Agency approved angiotensin II as a vasoconstrictor to raise blood pressure
      in patients with septic or other distributive shock who remain hypotensive despite adequate
      volume restitution and application of catecholamines and other available vasopressor
      therapies.

      Noradrenaline is currently recommended by the consensus guideline as the first line
      vasopressor for COVID-19 patients with vasodilatory shock. There is insufficient evidence to
      issue a treatment recommendation on the use of angiotensin II in critically ill adults with
      confirmed COVID-19 infection with ARDS and vasodilatory shock. Therefore, this study aims to
      compare the efficacy of angiotensin II as an add-on vasopressor with optimised standard of
      care.

      Critically ill patients with COVID-19 infection also often receive Anakinra to modulate the
      inflammatory response. The investigators would also like to collect the data of patients
      treated with and without Anakinra.
observational model: Case-Control
time perspective: Retrospective
measure: Proportions of patients with mean arterial pressure ≥ 65 mmHg or an increase of mean arterial pressure ≥10 mmHg at 3 hours
time frame: 3 hours
description: Percentage
measure: Noradrenaline dose
time frame: 1 hour and 3 hours
description: microgram/kg/min
measure: Sequential Organ Failure Assessment (SOFA) score
time frame: baseline, 24, and 48 hours
description: Changes in score, minimum 0, maximum 24, the higher score showing worse prognosis
measure: RRT-free days
time frame: 28 days
description: Patients who are alive and do not require renal replacement therapy at 28 days
measure: RRT discontinuation
time frame: 7 and 28 days
description: Proportions of patients who do not require renal replacement therapy
measure: Serum creatinine
time frame: 7 days and 28 days
description: micromol/L
measure: PaO2/FiO2 ratio
time frame: baseline, 24, and 48 hours
description: Changes in value
measure: Mortality
time frame: 7 days and 28 days
description: Mortality rate
measure: Adverse events
time frame: 28 days
description: e.g. arrhythmia, thromboembolism, etc.
measure: Change in serum C-reactive protein
time frame: 7 days
description: Change in serum C-reactive protein
measure: Change in serum ferritin
time frame: 7 days
description: Change in serum ferritin
arm group label: Angiotensin II
description: Patients with COVID-19 and acute respiratory distress syndrome who received angiotensin II as an add-on vasopressor will be collected
arm group label: Anakinra
description: Patients with COVID-19 and acute respiratory distress syndrome who received Anakinra (interleukin 1 receptor antagonist) will be collected
arm group label: Angiotensin II control
description: Patients with COVID-19 and acute respiratory distress syndrome who also received vasopressor support will be matched to angiotensin II group by date of intensive care unit admission, age, history of hypertension, history of angiotensin converting enzyme inhibitor/angiotensin receptor blocker, respiratory support
arm group label: Anakinra control
description: Patients with COVID-19 and acute respiratory distress syndrome will be matched to Anakinra group by matching age and date of intensive unit care admission
intervention type: Drug
intervention name: Angiotensin II
description: Exogenous angiotensin II acts on angiotensin II type 1 receptor and raise blood pressure by vasoconstriction, salt and water retention, and stimulation of aldosterone hormone
arm group label: Angiotensin II
intervention type: Drug
intervention name: Interleukin-1 receptor antagonist
description: Interleukin-1 receptor antagonist is an immunomodulating drug aiming to mitigate cytokine storm in COVID-19 patients
arm group label: Anakinra
other name: Anakinra
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marlies Ostermann
role: Principal Investigator
affiliation: Department of Critical Care, Guy's & St Thomas' Hospital
last name: Marlies Ostermann, MD, PhD
phone: 0044 207 188 3038
email: Marlies.Ostermann@gstt.nhs.uk
last name: Nuttha Lumlertgul, MD, PhD
phone: 0044 207 188 3038
email: Nuttha.Lumlertgul@gstt.nhs.uk
facility: 
status: Recruiting
contact: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Acute Lung Injury
mesh term: Syndrome
mesh term: Interleukin 1 Receptor Antagonist Protein
mesh term: Angiotensin II
mesh term: Giapreza
mesh term: Angiotensinogen
sharing ipd: Undecided