EARLY: Early Alirocumab to Reduce LDL-C in Myocardial Infarction

Sponsor

Imperial College London (Other)

Overall Status

Withdrawn

CT.gov ID

NCT03750760

Collaborator

Regeneron Pharmaceuticals (Industry), Baim Institute for Clinical Research (Other)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myocardial Infarction Dyslipidemias	Drug: Alirocumab Drug: Atorvastatin 80mg Drug: Ezetimibe 10mg	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Early Alirocumab to Reduce LDL-C in Myocardial Infarction

Anticipated Study Start Date :

Jan 1, 2020

Anticipated Primary Completion Date :

Dec 1, 2020

Anticipated Study Completion Date :

Dec 1, 2021

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

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

Sponsors and Collaborators

Imperial College London
Regeneron Pharmaceuticals
Baim Institute for Clinical Research

Investigators

Principal Investigator: Kausik Ray, Professor, Imperial College London

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Imperial College London

ClinicalTrials.gov Identifier:

NCT03750760

Other Study ID Numbers:

18HH4627
2018-002429-49

First Posted:

Nov 23, 2018

Last Update Posted:

Jun 13, 2019

Last Verified:

Jun 1, 2019

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Additional relevant MeSH terms:

Myocardial Infarction

Study Results

No Results Posted as of Jun 13, 2019