<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/NCT03750760</url>
  </required_header>
  <id_info>
    <org_study_id>18HH4627</org_study_id>
    <secondary_id>2018-002429-49</secondary_id>
    <nct_id>NCT03750760</nct_id>
  </id_info>
  <brief_title>Early Alirocumab to Reduce LDL-C in Myocardial Infarction</brief_title>
  <acronym>EARLY</acronym>
  <official_title>Early Alirocumab to Reduce LDL-C in Myocardial Infarction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Regeneron Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Baim Institute for Clinical Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Imperial College London</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>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The EARLY trial is a phase IV, investigator initiated, international, multicentre study that&#xD;
      will investigate if early use of alirocumab 150mg plus atorvastatin 80mg (enhanced care) will&#xD;
      have a greater effect than atorvastatin 80mg (standard care) on the reduction of LDL-C at&#xD;
      2-weeks after a myocardial infarction (MI), in patients who start treatment within 24 hours&#xD;
      of symptom onset.&#xD;
&#xD;
      A secondary goal is to assess the effects of enhanced care when compared to standard care&#xD;
      which is either atorvastatin alone or atorvastatin plus ezetimibe, (the latter added at 4&#xD;
      weeks if LDL-C is ≥ 70mg/dL (1.8mmol/L), on the proportion of patients achieving an LDL-C&#xD;
      goal of &lt; 50mg/dL (1.29 mmol/L) at 7 weeks after an MI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with Acute Coronary Syndrome (ACS), which includes myocardial infarction, are at&#xD;
      high risk of recurrent ischaemic events (e.g. heart attacks), and death. The current standard&#xD;
      treatment includes high dose statins to lower low-density lipoprotein cholesterol (LDL-C),&#xD;
      also known as bad cholesterol, soon after admission. In some cases, following assessment&#xD;
      after 1-3 months, administration of a second line cholesterol lowering therapy (ezetimibe)&#xD;
      may be added if LDL-C levels remain high ≥ 70mg/dL (1.8mmol/L). Many guidelines advocate that&#xD;
      following ACS high dose statins should be used as first line therapy. If LDL-C levels remain&#xD;
      greater than 70mg/dL (1.8mmol/L) then additional add on therapy on statins could be&#xD;
      considered for ACS patients.&#xD;
&#xD;
      Consented patients meeting the eligibility criteria for the EARLY trial will be randomised to&#xD;
      enhanced care or standard care within 24hrs of symptom onset for MI. Patients randomised to&#xD;
      enhanced care will receive alirocumab 150 mg on randomisation and then every 2 weeks during a&#xD;
      7-week treatment period. All patients will receive atorvastatin 80 mg. Patients randomised to&#xD;
      standard care with an LDL-C level ≥ 70mg/dL (1.8mmol/L) at week 4 will receive ezetimibe 10&#xD;
      mg, in addition to atorvastatin 80 mg for the remaining duration of the treatment period.&#xD;
&#xD;
      All patients will be followed up for a two-week period after completing the 7-week treatment&#xD;
      period (i.e. a total of 9 weeks to assess safety).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Changes in funding decision&#xD;
  </why_stopped>
  <start_date type="Anticipated">January 2020</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2020</primary_completion_date>
  <phase>Phase 4</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage change in LDL-C in enhanced care group verses standard of care group at 2 weeks after randomisation</measure>
    <time_frame>2 weeks from baseline</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage change in LDL-C at 7 weeks in enhanced care verses standard of care.</measure>
    <time_frame>7 weeks from baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients who achieve a LDL &lt; 50mg/dL (1.29mmol/L) at week 2, 4 and 7 in enhanced care verses standard of care</measure>
    <time_frame>2, 4 and 7 weeks from baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients in standard of care who need ezetimibe 10 mg to be added in the standard of care pathway at week 4</measure>
    <time_frame>4 weeks from baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with reported adverse events (AEs)</measure>
    <time_frame>7 and 9 weeks from baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with reported serious adverse events (SAEs)</measure>
    <time_frame>7 and 9 weeks from baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with reported adverse events of special interest (AESIs)</measure>
    <time_frame>7 and 9 weeks from baseline</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Myocardial Infarction</condition>
  <condition>Dyslipidemias</condition>
  <arm_group>
    <arm_group_label>Alirocumab (enhanced care)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Alirocumab (150 mg) administered by subcutaneous injection, every two weeks for 7 weeks.&#xD;
Atorvastatin (80 mg), oral administration daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Atorvastatin (standard care)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Atorvastatin (80 mg), oral administration daily. Ezetimibe (10 mg), oral administration daily, from week 4 if LDL-C is ≥ 70 mg/dL (1.8mmol/L) at week 4.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alirocumab</intervention_name>
    <description>PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) inhibitor antibody</description>
    <arm_group_label>Alirocumab (enhanced care)</arm_group_label>
    <other_name>Praluent</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atorvastatin 80mg</intervention_name>
    <description>3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statin)</description>
    <arm_group_label>Alirocumab (enhanced care)</arm_group_label>
    <arm_group_label>Atorvastatin (standard care)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ezetimibe 10mg</intervention_name>
    <description>Cholesterol absorption inhibitor</description>
    <arm_group_label>Atorvastatin (standard care)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males or females aged 18 years or above&#xD;
&#xD;
          -  Admitted to hospital for ST-Segment Elevation MI (STEMI) or non-ST-Segment Elevation&#xD;
             MI (NSTEMI) (proven by electrocardiogram (ECG) or biomarker evidence of MI)&#xD;
&#xD;
          -  Statin naïve prior to MI&#xD;
&#xD;
          -  Local LDL-C measurement available within 24 hrs of chest pain with no more than 1 dose&#xD;
             of statin&#xD;
&#xD;
          -  Ability and willingness to give written informed consent and to comply with the&#xD;
             requirements of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No ECG or biomarker evidence of MI&#xD;
&#xD;
          -  Received more than one dose of statin during the index event prior to randomisation&#xD;
&#xD;
          -  Contraindication to atorvastatin 80mg&#xD;
&#xD;
          -  Contraindication to ezetimibe&#xD;
&#xD;
          -  Contraindication to alirocumab&#xD;
&#xD;
          -  Unwillingness or inability to comply with study requirements, particularly with&#xD;
             respect to laboratory tests, specifically blood draws 24 and 48 hours after&#xD;
             randomisation, and subsequent clinic visits&#xD;
&#xD;
          -  New York Heart Association (NYHA) Class IV Heart Failure&#xD;
&#xD;
          -  Unstable arrhythmia&#xD;
&#xD;
          -  Subjects who in the opinion of investigator have a life expectancy of &lt; 9 weeks&#xD;
&#xD;
          -  Women of child bearing age who are not using at least 2 methods of contraception&#xD;
&#xD;
          -  Pregnant or breastfeeding.&#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>Kausik Ray, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Imperial College London</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Royal Devon &amp; Exeter Hospital</name>
      <address>
        <city>Exeter</city>
        <state>Devon</state>
        <zip>EX2 5DW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Royal Bournemouth General Hospital</name>
      <address>
        <city>Bournemouth</city>
        <state>Dorset</state>
        <zip>BH7 7DW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>East Sussex Healthcare NHS Trust</name>
      <address>
        <city>Saint Leonards-on-Sea</city>
        <state>East Sussex</state>
        <zip>TN37 7PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Basildon Hospital</name>
      <address>
        <city>Basildon</city>
        <state>Essex</state>
        <zip>SS16 5NL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Mary's Hospital</name>
      <address>
        <city>London</city>
        <state>Greater London</state>
        <zip>W2 1NY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Alexandra Hospital</name>
      <address>
        <city>Portsmouth</city>
        <state>Hampshire</state>
        <zip>PO6 3LY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southampton General Hospital</name>
      <address>
        <city>Southampton</city>
        <state>Hampshire</state>
        <zip>SO16 6YD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwick Park Hospital</name>
      <address>
        <city>Harrow</city>
        <state>Middlesex</state>
        <zip>HA1 3UJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hull Royal Infirmary</name>
      <address>
        <city>Hull</city>
        <state>North Humberside</state>
        <zip>HU3 2JZ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queens Medical Centre</name>
      <address>
        <city>Nottingham</city>
        <state>Nottinghamshire</state>
        <zip>NG7 2UH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Peters Hospital</name>
      <address>
        <city>Chertsey</city>
        <state>Surrey</state>
        <zip>KT16 0PZ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>East Surrey Hospital</name>
      <address>
        <city>Redhill</city>
        <state>Surrey</state>
        <zip>RH1 5RH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Freeman Hospital</name>
      <address>
        <city>Newcastle Upon Tyne</city>
        <state>Tyne And Wear</state>
        <zip>NE7 7DN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth Medical Centre</name>
      <address>
        <city>Birmingham</city>
        <state>West Midlands</state>
        <zip>B15 2TH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City Hospital</name>
      <address>
        <city>Birmingham</city>
        <state>West Midlands</state>
        <zip>B18 7QH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Worchestershire Royal Hospital</name>
      <address>
        <city>Worcester</city>
        <state>Worcestershire</state>
        <zip>WR5 1DD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northern General Hospital</name>
      <address>
        <city>Sheffield</city>
        <state>Yorkshire</state>
        <zip>S5 7AU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>November 19, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <last_update_submitted>June 11, 2019</last_update_submitted>
  <last_update_submitted_qc>June 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 13, 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>Myocardial Infarction</mesh_term>
    <mesh_term>Dyslipidemias</mesh_term>
    <mesh_term>Infarction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atorvastatin</mesh_term>
    <mesh_term>Ezetimibe</mesh_term>
    <mesh_term>Alirocumab</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/NCT03750760
org study id: 18HH4627
secondary id: 2018-002429-49
nct id: NCT03750760
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The EARLY trial is a phase IV, investigator initiated, international, multicentre study that
      will investigate if early use of alirocumab 150mg plus atorvastatin 80mg (enhanced care) will
      have a greater effect than atorvastatin 80mg (standard care) on the reduction of LDL-C at
      2-weeks after a myocardial infarction (MI), in patients who start treatment within 24 hours
      of symptom onset.

      A secondary goal is to assess the effects of enhanced care when compared to standard care
      which is either atorvastatin alone or atorvastatin plus ezetimibe, (the latter added at 4
      weeks if LDL-C is ≥ 70mg/dL (1.8mmol/L), on the proportion of patients achieving an LDL-C
      goal of < 50mg/dL (1.29 mmol/L) at 7 weeks after an MI.
Patients with Acute Coronary Syndrome (ACS), which includes myocardial infarction, are at
      high risk of recurrent ischaemic events (e.g. heart attacks), and death. The current standard
      treatment includes high dose statins to lower low-density lipoprotein cholesterol (LDL-C),
      also known as bad cholesterol, soon after admission. In some cases, following assessment
      after 1-3 months, administration of a second line cholesterol lowering therapy (ezetimibe)
      may be added if LDL-C levels remain high ≥ 70mg/dL (1.8mmol/L). Many guidelines advocate that
      following ACS high dose statins should be used as first line therapy. If LDL-C levels remain
      greater than 70mg/dL (1.8mmol/L) then additional add on therapy on statins could be
      considered for ACS patients.

      Consented patients meeting the eligibility criteria for the EARLY trial will be randomised to
      enhanced care or standard care within 24hrs of symptom onset for MI. Patients randomised to
      enhanced care will receive alirocumab 150 mg on randomisation and then every 2 weeks during a
      7-week treatment period. All patients will receive atorvastatin 80 mg. Patients randomised to
      standard care with an LDL-C level ≥ 70mg/dL (1.8mmol/L) at week 4 will receive ezetimibe 10
      mg, in addition to atorvastatin 80 mg for the remaining duration of the treatment period.

      All patients will be followed up for a two-week period after completing the 7-week treatment
      period (i.e. a total of 9 weeks to assess safety).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage change in LDL-C in enhanced care group verses standard of care group at 2 weeks after randomisation
time frame: 2 weeks from baseline
measure: Percentage change in LDL-C at 7 weeks in enhanced care verses standard of care.
time frame: 7 weeks from baseline
measure: Proportion of patients who achieve a LDL < 50mg/dL (1.29mmol/L) at week 2, 4 and 7 in enhanced care verses standard of care
time frame: 2, 4 and 7 weeks from baseline
measure: Proportion of patients in standard of care who need ezetimibe 10 mg to be added in the standard of care pathway at week 4
time frame: 4 weeks from baseline
measure: Proportion of patients with reported adverse events (AEs)
time frame: 7 and 9 weeks from baseline
measure: Proportion of patients with reported serious adverse events (SAEs)
time frame: 7 and 9 weeks from baseline
measure: Proportion of patients with reported adverse events of special interest (AESIs)
time frame: 7 and 9 weeks from baseline
arm group label: Alirocumab (enhanced care)
arm group type: Active Comparator
description: Alirocumab (150 mg) administered by subcutaneous injection, every two weeks for 7 weeks.
Atorvastatin (80 mg), oral administration daily.
arm group label: Atorvastatin (standard care)
arm group type: Active Comparator
description: Atorvastatin (80 mg), oral administration daily. Ezetimibe (10 mg), oral administration daily, from week 4 if LDL-C is ≥ 70 mg/dL (1.8mmol/L) at week 4.
intervention type: Drug
intervention name: Alirocumab
description: PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) inhibitor antibody
arm group label: Alirocumab (enhanced care)
other name: Praluent
intervention type: Drug
intervention name: Atorvastatin 80mg
description: 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statin)
arm group label: Alirocumab (enhanced care)
arm group label: Atorvastatin (standard care)
intervention type: Drug
intervention name: Ezetimibe 10mg
description: Cholesterol absorption inhibitor
arm group label: Atorvastatin (standard care)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kausik Ray, Professor
role: Principal Investigator
affiliation: Imperial College London
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Myocardial Infarction
mesh term: Dyslipidemias
mesh term: Infarction
mesh term: Atorvastatin
mesh term: Ezetimibe
mesh term: Alirocumab
sharing ipd: No