Early Alirocumab to Reduce LDL-C in Myocardial Infarction

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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Early Alirocumab to Reduce LDL-C in Myocardial Infarction

Conditions
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Myocardial Infarction, Dyslipidemias

Intervention / Treatment
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* Drug: Alirocumab
* Drug: Atorvastatin 80mg
* Drug: Ezetimibe 10mg


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |