Early Alirocumab to Reduce LDL-C in Myocardial Infarction

NCT03750760 | Withdrawn Phase 4 FDA Drug

• 2 other identifiers: 18HH46272018-002429-49
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 17

Brief Summary

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.

Conditions

Myocardial Infarction; Dyslipidemias

Outcome Measures

Primary Outcomes (1)

• Percentage change in LDL-C in enhanced care group verses standard of care group at 2 weeks after randomisation

  2 weeks from baseline

Secondary Outcomes (6)

• 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

Study Arms (2)

Alirocumab (enhanced care)

ACTIVE COMPARATOR

Alirocumab (150 mg) administered by subcutaneous injection, every two weeks for 7 weeks. Atorvastatin (80 mg), oral administration daily.

Drug: Alirocumab; Drug: Atorvastatin 80mg

Atorvastatin (standard care)

ACTIVE COMPARATOR

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; Drug: Ezetimibe 10mg

Interventions

Alirocumab DRUG

PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) inhibitor antibody

Also known as: Praluent

Alirocumab (enhanced care)

Atorvastatin 80mg DRUG

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statin)

Alirocumab (enhanced care); Atorvastatin (standard care)

Ezetimibe 10mg DRUG

Cholesterol absorption inhibitor

Atorvastatin (standard care)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Imperial College London: lead
• Regeneron Pharmaceuticals: collaborator
• Baim Institute for Clinical Research: collaborator

Study Sites (17)

Royal Devon & Exeter Hospital

Exeter, Devon, EX2 5DW, United Kingdom

Location

The Royal Bournemouth General Hospital

Bournemouth, Dorset, BH7 7DW, United Kingdom

Location

East Sussex Healthcare NHS Trust

Saint Leonards-on-Sea, East Sussex, TN37 7PT, United Kingdom

Location

Basildon Hospital

Basildon, Essex, SS16 5NL, United Kingdom

Location

St Mary's Hospital

London, Greater London, W2 1NY, United Kingdom

Location

Queen Alexandra Hospital

Portsmouth, Hampshire, PO6 3LY, United Kingdom

Location

Southampton General Hospital

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Northwick Park Hospital

Harrow, Middlesex, HA1 3UJ, United Kingdom

Location

Hull Royal Infirmary

Hull, North Humberside, HU3 2JZ, United Kingdom

Location

Queens Medical Centre

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

Location

St Peters Hospital

Chertsey, Surrey, KT16 0PZ, United Kingdom

Location

East Surrey Hospital

Redhill, Surrey, RH1 5RH, United Kingdom

Location

Freeman Hospital

Newcastle upon Tyne, Tyne and Wear, NE7 7DN, United Kingdom

Location

Queen Elizabeth Medical Centre

Birmingham, West Midlands, B15 2TH, United Kingdom

Location

City Hospital

Birmingham, West Midlands, B18 7QH, United Kingdom

Location

Worchestershire Royal Hospital

Worcester, Worcestershire, WR5 1DD, United Kingdom

Location

Northern General Hospital

Sheffield, Yorkshire, S5 7AU, United Kingdom

Location

MeSH Terms

Conditions

Myocardial Infarction; Dyslipidemias

Interventions

alirocumab; Atorvastatin; Ezetimibe

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Azetidines; Azetines

Study Officials

• Kausik Ray, Professor

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2018
• First Posted: November 23, 2018
• Study Start: January 1, 2020
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2021
• Last Updated: June 13, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (17)