Early Alirocumab to Reduce LDL-C in Myocardial Infarction

Myocardial Infarction Clinical Trial

— EARLY  

Official title:

Early Alirocumab to Reduce LDL-C in Myocardial Infarction

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03750760
• Other study ID #: 18HH4627
• Secondary ID: 2018-002429-49
• Status: Withdrawn
• Phase: Phase 4
• Start date: January 2020
• Est. completion date: December 2021

Study information

• Verified date: June 2019
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Dyslipidemias
• Infarction
• Myocardial Infarction

Intervention

Drug:
• Alirocumab
PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) inhibitor antibody
• Atorvastatin 80mg
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statin)
• Ezetimibe 10mg
Cholesterol absorption inhibitor

Locations

Country	Name	City	State
United Kingdom	Basildon Hospital	Basildon	Essex
United Kingdom	City Hospital	Birmingham	West Midlands
United Kingdom	Queen Elizabeth Medical Centre	Birmingham	West Midlands
United Kingdom	The Royal Bournemouth General Hospital	Bournemouth	Dorset
United Kingdom	St Peters Hospital	Chertsey	Surrey
United Kingdom	Royal Devon & Exeter Hospital	Exeter	Devon
United Kingdom	Northwick Park Hospital	Harrow	Middlesex
United Kingdom	Hull Royal Infirmary	Hull	North Humberside
United Kingdom	St Mary's Hospital	London	Greater London
United Kingdom	Freeman Hospital	Newcastle Upon Tyne	Tyne And Wear
United Kingdom	Queens Medical Centre	Nottingham	Nottinghamshire
United Kingdom	Queen Alexandra Hospital	Portsmouth	Hampshire
United Kingdom	East Surrey Hospital	Redhill	Surrey
United Kingdom	East Sussex Healthcare NHS Trust	Saint Leonards-on-Sea	East Sussex
United Kingdom	Northern General Hospital	Sheffield	Yorkshire
United Kingdom	Southampton General Hospital	Southampton	Hampshire
United Kingdom	Worchestershire Royal Hospital	Worcester	Worcestershire

Sponsors (3)

Lead Sponsor	Collaborator
Imperial College London	Baim Institute for Clinical Research, Regeneron Pharmaceuticals

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage change in LDL-C in enhanced care group verses standard of care group at 2 weeks after randomisation		2 weeks from baseline
Secondary	Percentage change in LDL-C at 7 weeks in enhanced care verses standard of care.		7 weeks from baseline
Secondary	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
Secondary	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
Secondary	Proportion of patients with reported adverse events (AEs)		7 and 9 weeks from baseline
Secondary	Proportion of patients with reported serious adverse events (SAEs)		7 and 9 weeks from baseline
Secondary	Proportion of patients with reported adverse events of special interest (AESIs)		7 and 9 weeks from baseline