Early Alirocumab to Reduce LDL-C in Myocardial Infarction (EARLY)

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.

Study Overview

• Status: Withdrawn
• Conditions: Myocardial Infarction; Dyslipidemias
• Intervention / Treatment: Drug: Alirocumab; Drug: Atorvastatin 80mg; Drug: Ezetimibe 10mg

Detailed Description

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).

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Devon
    • Exeter, Devon, United Kingdom, EX2 5DW
      • Royal Devon & Exeter Hospital
  • Dorset
    • Bournemouth, Dorset, United Kingdom, BH7 7DW
      • The Royal Bournemouth General Hospital
  • East Sussex
    • Saint Leonards-on-Sea, East Sussex, United Kingdom, TN37 7PT
      • East Sussex Healthcare Nhs Trust
  • Essex
    • Basildon, Essex, United Kingdom, SS16 5NL
      • Basildon Hospital
  • Greater London
    • London, Greater London, United Kingdom, W2 1NY
      • St Mary's Hospital
  • Hampshire
    • Portsmouth, Hampshire, United Kingdom, PO6 3LY
      • Queen Alexandra Hospital
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Southampton General Hospital
  • Middlesex
    • Harrow, Middlesex, United Kingdom, HA1 3UJ
      • Northwick Park Hospital
  • North Humberside
    • Hull, North Humberside, United Kingdom, HU3 2JZ
      • Hull Royal Infirmary
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
      • Queens Medical Centre
  • Surrey
    • Chertsey, Surrey, United Kingdom, KT16 0PZ
      • St Peters Hospital
    • Redhill, Surrey, United Kingdom, RH1 5RH
      • East Surrey Hospital
  • Tyne And Wear
    • Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NE7 7DN
      • Freeman Hospital
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B15 2TH
      • Queen Elizabeth Medical Centre
    • Birmingham, West Midlands, United Kingdom, B18 7QH
      • City Hospital
  • Worcestershire
    • Worcester, Worcestershire, United Kingdom, WR5 1DD
      • Worchestershire Royal Hospital
  • Yorkshire
    • Sheffield, Yorkshire, United Kingdom, S5 7AU
      • Northern General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males or females aged 18 years or above
• Admitted to hospital for ST-Segment Elevation MI (STEMI) or non-ST-Segment Elevation MI (NSTEMI) (proven by electrocardiogram (ECG) or biomarker evidence of MI)
• Statin naïve prior to MI
• Local LDL-C measurement available within 24 hrs of chest pain with no more than 1 dose of statin
• Ability and willingness to give written informed consent and to comply with the requirements of the study

Exclusion Criteria:

• No ECG or biomarker evidence of MI
• Received more than one dose of statin during the index event prior to randomisation
• Contraindication to atorvastatin 80mg
• Contraindication to ezetimibe
• Contraindication to alirocumab
• Unwillingness or inability to comply with study requirements, particularly with respect to laboratory tests, specifically blood draws 24 and 48 hours after randomisation, and subsequent clinic visits
• New York Heart Association (NYHA) Class IV Heart Failure
• Unstable arrhythmia
• Subjects who in the opinion of investigator have a life expectancy of < 9 weeks
• Women of child bearing age who are not using at least 2 methods of contraception
• Pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Alirocumab (enhanced care); Alirocumab (150 mg) administered by subcutaneous injection, every two weeks for 7 weeks. Atorvastatin (80 mg), oral administration daily.	Drug: Alirocumab; PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) inhibitor antibody; Other Names: Praluent; Drug: Atorvastatin 80mg; 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statin)
Active Comparator: Atorvastatin (standard care); 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.	Drug: Atorvastatin 80mg; 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statin); Drug: Ezetimibe 10mg; Cholesterol absorption inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage change in LDL-C in enhanced care group verses standard of care group at 2 weeks after randomisation	2 weeks from baseline

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage change in LDL-C at 7 weeks in enhanced care verses standard of care.	7 weeks from baseline
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	2, 4 and 7 weeks from baseline
Proportion of patients in standard of care who need ezetimibe 10 mg to be added in the standard of care pathway at week 4	4 weeks from baseline
Proportion of patients with reported adverse events (AEs)	7 and 9 weeks from baseline
Proportion of patients with reported serious adverse events (SAEs)	7 and 9 weeks from baseline
Proportion of patients with reported adverse events of special interest (AESIs)	7 and 9 weeks from baseline

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Regeneron Pharmaceuticals; Baim Institute for Clinical Research
• Investigators: Principal Investigator: Kausik Ray, Professor, Imperial College London

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2020
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: November 19, 2018
• First Submitted That Met QC Criteria: November 20, 2018
• First Posted (Actual): November 23, 2018

Study Record Updates

• Last Update Posted (Actual): June 13, 2019
• Last Update Submitted That Met QC Criteria: June 11, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Lipid Metabolism Disorders; Myocardial Infarction; Infarction; Dyslipidemias; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Ezetimibe
• Other Study ID Numbers: 18HH4627; 2018-002429-49 (Other Grant/Funding Number: R727-CV-17108)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes