Clinical trial NCT03750760: Early Alirocumab to Reduce LDL-C in Myocardial Infarction
Official title: Early Alirocumab to Reduce LDL-C in Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Myocardial Infarction
Dyslipidemias
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Regeneron Pharmaceuticals
name: Baim Institute for Clinical Research
First posted: 2018-11-23
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage change in LDL-C in enhanced care group verses standard of care group at 2 weeks after randomisation
timeFrame: 2 weeks from baseline
Secondary outcomes:
measure: Percentage change in LDL-C at 7 weeks in enhanced care verses standard of care.
timeFrame: 7 weeks from baseline
measure: 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
timeFrame: 2, 4 and 7 weeks from baseline
measure: Proportion of patients in standard of care who need ezetimibe 10 mg to be added in the standard of care pathway at week 4
timeFrame: 4 weeks from baseline
measure: Proportion of patients with reported adverse events (AEs)
timeFrame: 7 and 9 weeks from baseline
measure: Proportion of patients with reported serious adverse events (SAEs)
timeFrame: 7 and 9 weeks from baseline
measure: Proportion of patients with reported adverse events of special interest (AESIs)
timeFrame: 7 and 9 weeks from baseline
Other outcomes:
Locations:
city: Exeter
country: United Kingdom
facility: Royal Devon & Exeter Hospital
state: Devon
city: Bournemouth
country: United Kingdom
facility: The Royal Bournemouth General Hospital
state: Dorset
city: Saint Leonards-on-Sea
country: United Kingdom
facility: East Sussex Healthcare NHS Trust
state: East Sussex
city: Basildon
country: United Kingdom
facility: Basildon Hospital
state: Essex
city: London
country: United Kingdom
facility: St Mary's Hospital
state: Greater London
city: Portsmouth
country: United Kingdom
facility: Queen Alexandra Hospital
state: Hampshire
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: Hampshire
city: Harrow
country: United Kingdom
facility: Northwick Park Hospital
state: Middlesex
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
state: North Humberside
city: Nottingham
country: United Kingdom
facility: Queens Medical Centre
state: Nottinghamshire
city: Chertsey
country: United Kingdom
facility: St Peters Hospital
state: Surrey
city: Redhill
country: United Kingdom
facility: East Surrey Hospital
state: Surrey
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital
state: Tyne And Wear
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Medical Centre
state: West Midlands
city: Birmingham
country: United Kingdom
facility: City Hospital
state: West Midlands
city: Worcester
country: United Kingdom
facility: Worchestershire Royal Hospital
state: Worcestershire
city: Sheffield
country: United Kingdom
facility: Northern General Hospital
state: Yorkshire
Study officials:
affiliation: Imperial College London
name: Kausik Ray, Professor
role: PRINCIPAL_INVESTIGATOR
References: