Acute Coronary SyndromePhase 3EVOPACSNCT03287609

EVOlocumab for Early Reduction of LDL-cholesterol Levels in Patients With Acute Coronary Syndromes (EVOPACS)

A Phase 3 study testing Evolocumab 140 mg/mL in people with Acute Coronary Syndrome, run by Insel Gruppe AG, University Hospital Bern at 7 sites in Switzerland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Acute Coronary Syndrome
What is being tested?: Evolocumab 140 mg/mL
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 308 participants
Where: 7 sitesSwitzerland
Study dates: 23 Jan 2018to 7 Aug 2019
Phase: Phase 3
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female ≥ 18 years of age;
Hospitalized for a recent ACS;
LDL-C levels defined as follows:
LDL-C ≥70 mg/dL (≥1.8 mmol/L) or non-HDL-C ≥100 mg/dL (≥2.6 mmol/) in patients who have been receiving stable treatment with high-intensity statin within ≥ 4 weeks prior to enrollment (i.e. continuous treatment that has not changed with regard to statin intensity over the past 4 weeks) or, LDL-C ≥90 mg/dL (≥2.3 mmol/L) or non-HDL-C ≥120 mg/dL (≥3.1 mmol/) in patients who have been receiving stable treatment with low- or moderate-intensity statin within ≥ 4 weeks prior to enrollment (i.e. continuous treatment that has not changed with regard to statin intensity over the past 4 weeks), or LDL-C ≥125 mg/dL (≥3.2 mmol/L) or non-HDL-C ≥155 mg/dL (≥4.0 mmol/) in patients who are statin-naïve or have not been on a stable (unchanged) statin regimen for at least 4 weeks prior to enrollment;
Ability to understand the requirements of the study and to provide informed consent.

Who cannot join

Unstable clinical status (hemodynamic or electrical instability;
Uncontrolled cardiac arrhythmia, defined as recurrent and symptomatic ventricular tachycardia or atrial fibrillation with rapid ventricular response not controlled by medications in the past 3 months prior to screening;
Severe renal dysfunction, defined by estimated glomerular filtration rate <30 ml/min/1.73m2;
Active liver disease or hepatic dysfunction, either reported in patient medical record or defined by asparate aminotransferase (AST) or alanine aminotransferase (ALT) levels > 3x the upper limit of normal;
Reported intolerance to atorvastatin (any dose) OR statin intolerance;
Known allergy to contrast medium, heparin, aspirin, ticagrelor or prasugrel;

Show all 15Show fewer

Known sensitivity to any substances to be administered;
Patients who previously received evolocumab or other PCSK9 inhibitor;
Patient who received cholesterol ester transfer protein inhibitors in the past 12 months prior to screening;
Treatment with systemic steroids or systemic cyclosporine in the past 3 months systemic cyclosporine, systemic steroids (eg. intravenous, intramuscular or per os);
Known active infection or major hematologic, metabolic, or endocrine dysfunction in the judgment of the Investigator;
Patients who will not be available for study-required procedures in the judgment of the Investigator;
Current enrollment in another investigational device or drug study;
Active malignancy requiring treatment;
Female of childbearing potential (age <50 years and last menstruation within the last 12 months), who did not undergo tubal ligation, ovariectomy or hysterectomy.

Trial locations and contacts

7 sites in 1 country.

City, postcode or hospital

7 sites in 1 country

Switzerland7 sites

Basel University Hospital
Basel, Canton of Basel-City, 4031
Bern University Hospital
Bern, 3010
HFR Kantonsspital
Fribourg, Canton of Fribourg, 1708
Hopitaux Universitaires Geneve
Geneva, Canton of Geneva, 1211
Centre Hospitalier Universitaire Vaudois
Lausanne, Canton of Vaud
Cardiocentro Ticino
Lugano, Canton Ticino, 6900
University Hospital
Zurich, Canton of Zurich

Other trials in Switzerland

About this study

Official title: EVOlocumab for Early Reduction of LDL-cholesterol Levels in Patients With Acute Coronary Syndromes (EVOPACS) - A Randomized, Double-blind, Placebo-controlled Multicenter Study

Reduction of low-density lipoprotein cholesterol (LDL-C) levels effectively reduces the risk of adverse events in patients with established atherosclerotic cardiovascular disease. The clinical benefit of statins in improving clinical outcomes is proportional to the magnitude of LDL-C reduction, is more pronounced in patients with acute coronary syndromes (ACS) compared with stable coronary artery disease, and emerges at very early stages (as early as 4 weeks) after ACS when statins are administered in the acute phase of the event. On the basis of this evidence, early initiation of statin therapy is currently recommended in patients presenting with ACS. Because many patients cannot achieve adequate reduction of LDL-C levels despite treatment with high doses of statins or non-statin lipid-modifying medications, substantial residual risk remains. Moreover, the time of onset of LDL-C reduction takes 2 weeks following initiation of statin therapy. Proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors represent a novel class of lipid-lowering drugs leading to rapid, profound, and consistent reductions in LDL-C levels. While the effectiveness of PCSK9 monoclonal antibodies for LDL-C lowering has been established across patient populations without atherosclerotic cardiovascular disease or with stable ischemic heart disease, reduction and attainment of LDL-C target levels has not been explored in the acute setting of ACS - a clinical setting with highest risk of early event recurrence (within the first month). In this study the investigators want to evaluate the safety and effectiveness of the PCSK9 inhibitor evolocumab as compared with placebo, administered in the acute phase of ACS, for reduction of LDL-C levels within 8 weeks in patients receiving guideline-recommended high-intensity statin treatment (atorvastatin 40mg QD).

Conditions: Acute Coronary Syndrome
Being tested: Evolocumab 140 mg/mL, Placebo
Medical subject headings: Acute Coronary Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Evolocumab 140 mg/mLDrug
Three injections with pre-filled auto-injector pen at day 1 and at week 4.
PlaceboDrug
Three injections with pre-filled auto-injector pen at day 1 and at week 4.

Study groups in NCT03287609
Study group	Role	What they receive
Evolocumab	Active comparator	Evolocumab 140 mg/mL, pre-filled auto-injector pen, 3 injections at day 1 and week 4 Receives: Drug: Evolocumab 140 mg/mL
Placebo	Placebo comparator	Placebo, pre-filled auto-injector pen, 3 injections at day 1 and week 4 Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Percent change in calculated LDL-C in the intent to treat (ITT) population
Measured: Baseline to week 8

Secondary outcomes (1)

Number of patients with adverse events and serious adverse events
Measured: Baseline to week 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Jan 20187 Aug 2019

First posted19 Sep 2017
Study start23 Jan 2018
Primary completion20 May 2019
Study completion7 Aug 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (6)Papers the sponsor has linked to this study.
Other trials for Acute Coronary SyndromeStudies of the same condition, open and under way.
More trials run by Insel Gruppe AG, University Hospital BernThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 308 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03287609
Sponsor's protocol ID: 2017-01753
Other IDs: 2017
Acronym: EVOPACS
Status last verified: Aug 2019
First submitted: 7 Sep 2017
Last updated: 14 Aug 2019
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: No plan to make individual participant data available to other researchers

Publications

Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM, Sever PS, Pedersen TR; FOURIER Steering Committee and Investigators. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017 May 4;376(18):1713-1722. doi: 10.1056/NEJMoa1615664. Epub 2017 Mar 17.
PubMed 28304224
Lipinski MJ, Benedetto U, Escarcega RO, Biondi-Zoccai G, Lhermusier T, Baker NC, Torguson R, Brewer HB Jr, Waksman R. The impact of proprotein convertase subtilisin-kexin type 9 serine protease inhibitors on lipid levels and outcomes in patients with primary hypercholesterolaemia: a network meta-analysis. Eur Heart J. 2016 Feb 7;37(6):536-45. doi: 10.1093/eurheartj/ehv563. Epub 2015 Nov 17.
PubMed 26578202
Ray KK, Cannon CP, McCabe CH, Cairns R, Tonkin AM, Sacks FM, Jackson G, Braunwald E; PROVE IT-TIMI 22 Investigators. Early and late benefits of high-dose atorvastatin in patients with acute coronary syndromes: results from the PROVE IT-TIMI 22 trial. J Am Coll Cardiol. 2005 Oct 18;46(8):1405-10. doi: 10.1016/j.jacc.2005.03.077.
PubMed 16226162
Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, Zeiher A, Chaitman BR, Leslie S, Stern T; Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001 Apr 4;285(13):1711-8. doi: 10.1001/jama.285.13.1711.
PubMed 11277825
Navarese EP, Kolodziejczak M, Kereiakes DJ, Tantry US, O'Connor C, Gurbel PA. Proprotein Convertase Subtilisin/Kexin Type 9 Monoclonal Antibodies for Acute Coronary Syndrome: A Narrative Review. Ann Intern Med. 2016 May 3;164(9):600-7. doi: 10.7326/M15-2994. Epub 2016 Mar 22.
PubMed 26999484
Koskinas KC, Windecker S, Pedrazzini G, Mueller C, Cook S, Matter CM, Muller O, Haner J, Gencer B, Crljenica C, Amini P, Deckarm O, Iglesias JF, Raber L, Heg D, Mach F. Evolocumab for Early Reduction of LDL Cholesterol Levels in Patients With Acute Coronary Syndromes (EVOPACS). J Am Coll Cardiol. 2019 Nov 19;74(20):2452-2462. doi: 10.1016/j.jacc.2019.08.010. Epub 2019 Aug 31.
PubMed 31479722

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Acute Coronary Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: EVOlocumab for Early Reduction of LDL-cholesterol Levels in Patients With Acute Coronary Syndromes (EVOPACS) - A Randomized, Double-blind, Placebo-controlled Multicenter Study
ClinicalTrials.gov ID: NCT03287609
Acronym / sponsor ID: EVOPACS / 2017-01753
Conditions: Acute Coronary Syndrome
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 308 participants (actual)
Lead sponsor: Insel Gruppe AG, University Hospital BernUniversity, hospital or other
Collaborators: Amgen, University of Bern
Study start: 23 Jan 2018 (actual)
Primary completion: 20 May 2019 (actual)
Study completion: 7 Aug 2019 (actual)
First posted: 19 Sep 2017 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Evolocumab	Active comparator	Drug: Evolocumab 140 mg/mLEvolocumab 140 mg/mL, pre-filled auto-injector pen, 3 injections at day 1 and week 4
Placebo	Placebo comparator	Drug: PlaceboPlacebo, pre-filled auto-injector pen, 3 injections at day 1 and week 4

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Male or female ≥ 18 years of age;
Hospitalized for a recent ACS;
LDL-C levels defined as follows:
LDL-C ≥70 mg/dL (≥1.8 mmol/L) or non-HDL-C ≥100 mg/dL (≥2.6 mmol/) in patients who have been receiving stable treatment with high-intensity statin within ≥ 4 weeks prior to enrollment (i.e. continuous treatment that has not changed with regard to statin intensity over the past 4 weeks) or, LDL-C ≥90 mg/dL (≥2.3 mmol/L) or non-HDL-C ≥120 mg/dL (≥3.1 mmol/) in patients who have been receiving stable treatment with low- or moderate-intensity statin within ≥ 4 weeks prior to enrollment (i.e. continuous treatment that has not changed with regard to statin intensity over the past 4 weeks), or LDL-C ≥125 mg/dL (≥3.2 mmol/L) or non-HDL-C ≥155 mg/dL (≥4.0 mmol/) in patients who are statin-naïve or have not been on a stable (unchanged) statin regimen for at least 4 weeks prior to enrollment;
Ability to understand the requirements of the study and to provide informed consent.

Key exclusion criteria (15 listed)

Unstable clinical status (hemodynamic or electrical instability;
Uncontrolled cardiac arrhythmia, defined as recurrent and symptomatic ventricular tachycardia or atrial fibrillation with rapid ventricular response not controlled by medications in the past 3 months prior to screening;
Severe renal dysfunction, defined by estimated glomerular filtration rate <30 ml/min/1.73m2;
Active liver disease or hepatic dysfunction, either reported in patient medical record or defined by asparate aminotransferase (AST) or alanine aminotransferase (ALT) levels > 3x the upper limit of normal;
Reported intolerance to atorvastatin (any dose) OR statin intolerance;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Evolocumab 140 mg/mLThree injections with pre-filled auto-injector pen at day 1 and at week 4.	Drug	Evolocumab
PlaceboThree injections with pre-filled auto-injector pen at day 1 and at week 4.	Drug	Placebo

Primary outcome

Percent change in calculated LDL-C in the intent to treat (ITT) population
Time frame: Baseline to week 8

1 secondary outcome

Number of patients with adverse events and serious adverse events
Time frame: Baseline to week 8

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2019.
Results publication: PubMed 28304224Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM, Sever PS, Pedersen TR; FOURIER Steering Committee and Investigators. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017 May 4;376(18):1713-1722. doi: 10.1056/NEJMoa1615664. Epub 2017 Mar 17.
Results publication: PubMed 26578202Lipinski MJ, Benedetto U, Escarcega RO, Biondi-Zoccai G, Lhermusier T, Baker NC, Torguson R, Brewer HB Jr, Waksman R. The impact of proprotein convertase subtilisin-kexin type 9 serine protease inhibitors on lipid levels and outcomes in patients with primary hypercholesterolaemia: a network meta-analysis. Eur Heart J. 2016 Feb 7;37(6):536-45. doi: 10.1093/eurheartj/ehv563. Epub 2015 Nov 17.
Results publication: PubMed 16226162Ray KK, Cannon CP, McCabe CH, Cairns R, Tonkin AM, Sacks FM, Jackson G, Braunwald E; PROVE IT-TIMI 22 Investigators. Early and late benefits of high-dose atorvastatin in patients with acute coronary syndromes: results from the PROVE IT-TIMI 22 trial. J Am Coll Cardiol. 2005 Oct 18;46(8):1405-10. doi: 10.1016/j.jacc.2005.03.077.
Results publication: PubMed 11277825Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, Zeiher A, Chaitman BR, Leslie S, Stern T; Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001 Apr 4;285(13):1711-8. doi: 10.1001/jama.285.13.1711.
Results publication: PubMed 26999484Navarese EP, Kolodziejczak M, Kereiakes DJ, Tantry US, O'Connor C, Gurbel PA. Proprotein Convertase Subtilisin/Kexin Type 9 Monoclonal Antibodies for Acute Coronary Syndrome: A Narrative Review. Ann Intern Med. 2016 May 3;164(9):600-7. doi: 10.7326/M15-2994. Epub 2016 Mar 22.
Derived from this study: PubMed 31479722Koskinas KC, Windecker S, Pedrazzini G, Mueller C, Cook S, Matter CM, Muller O, Haner J, Gencer B, Crljenica C, Amini P, Deckarm O, Iglesias JF, Raber L, Heg D, Mach F. Evolocumab for Early Reduction of LDL Cholesterol Levels in Patients With Acute Coronary Syndromes (EVOPACS). J Am Coll Cardiol. 2019 Nov 19;74(20):2452-2462. doi: 10.1016/j.jacc.2019.08.010. Epub 2019 Aug 31.
Individual participant dataSharing planned: No. No plan to make individual participant data available to other researchers

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Stephan Windecker, Prof., MD study chair

Bern University Hospital

Konstantinos Koskinas, MD principal investigator

Bern University Hospital

7 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Evolocumab 140 mg/mL in people with Acute Coronary Syndrome, run by Insel Gruppe AG, University Hospital Bern at 7 sites in Switzerland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent change in calculated LDL-C in the intent to treat (ITT) population (time frame: Baseline to week 8). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03287609, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2019.