Acute Coronary SyndromesPhase 1/2CLEVER-ACSNCT01529554
Controlled Level EVERolimus in Acute Coronary Syndromes
A Phase 1/2 study testing Everolimus in people with Acute Coronary Syndromes, run by University of Zurich at 8 sites in 2 countries.
Trial summary
Acute myocardial infarction (AMI) constitutes the major cause of death in most nations and death rates and morbidity remain substantial in the years thereafter. Inflammation is a hallmark throughout the distinct stages of atherosclerotic lesion formation preceding AMI as well as at the time of plaque rupture and… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Acute Coronary Syndromes
- What is being tested?
- Everolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 8 Jan 2015to 29 Nov 2021
- Phase
- Phase 1/2
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Elevation Myocardial Infarction (STEMI) as defined by:
- ST-Elevation > 1mm in > 2 leads OR
- Novel left bundle branch block (LBBB) OR
- Posterior MI with ST-Depression > 1mm in > 2 leads
- Chest pain duration of > 10 minutes
- Primary Coronary Intervention (PCI) with drug-eluting stent (DES) within 24 hours of chest pain onset in the occluded culprit artery
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- First Myocardial Infarction
- Occluded coronary artery at angiography specifically occlusion of one coronary vessel in the proximal third of either LAD, RCX or RCA, the mid segment of right coronary artery (RCA) or mid segment of a large left anterior descending (LAD) coronary artery, i.e. when the latter reaches the apex.
- Male and female patients 18 years to 90 years of age
- Signed informed consent
Who cannot join
- Participation in another drug or stent trial
- Pregnant women or nursing mothers
- Mechanical complication during acute coronary syndrome
- Scheduled PCI for additional lesion within 30 days
- Multivessel disease
- Major elective surgery planned in trial period
Show all 10Show fewer
- Malignancy (unless healed or remission > 5 years)
- Chronic infection (HIV, Tbc, empyema)
- Severely compromised renal function (GFR< 30 ml/min)
- Positive PCR Test for SARS-CoV-2 and/or at least one positive answer to questions regarding symptoms/contact related to COVID-19.
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
Germany4 sites
Kerckhoff-Klinik, Department of Cardiology
Bad Nauheim
University Hospital Chartié
Berlin
University Hospital Duesseldorf
Düsseldorf
University Hospital Mainz
Mainz
Switzerland4 sites
University Hospital Bern
Bern
University Hospital Geneva
Geneva
Cardiocentro Ticino
Lugano
University Hospital Zurich
Zurich
About this study
Official title: Phase I-II Randomized Prospective Double-blind Multi-center Trial on the Effects of a Short Course of Oral Everolimus on Infarct Size, Left Ventricular Remodeling and Inflammation in Patients With Acute ST-Elevation Myocardial Infarction
Acute myocardial infarction (AMI) constitutes the major cause of death in most nations and death rates and morbidity remain substantial in the years thereafter. Inflammation is a hallmark throughout the distinct stages of atherosclerotic lesion formation preceding AMI as well as at the time of plaque rupture and during the post-infarct repair phase. Harnessing its harmful consequences constitutes an attractive therapeutic approach to address this unmet medical need.
The objectives of this study are to evaluate the effects of mTOR inhibition (everolimus) on infarct size, myocardial function and inflammation in patients with ST-Elevation Myocardial Infarction.
Read more
The efficacy objectives are:
- (1° endpoint): To assess the effect of mTOR inhibition (everolimus) on myocardial infarct size as change from baseline (12-72 hours after percutaneous coronary intervention) to 30 days follow-up measured by MRI (Late Gadolinium Enhancement (LGE) for transmurality).
- (2° endpoint): To evaluate microvascular obstruction (MVO) as change from baseline (12-72 hours after percutaneous coronary intervention) to 30 days follow-up evaluated by MRI.
- (3° endpoints):
- Change of left ventricular volume from baseline (12-72 hours after percutaneous coronary intervention) to 30 days follow-up measured by MRI.
- Change of biomarkers from time of coronary angiography to 30 days follow-up including a time-course (AUC). Biomarkers comprise hs-TnT, NT-proBNP, hs-CRP, IL-6 and inflammatory biomarkers OPG, sRANKL, OPN and CCN1.
The safety objectives are:
To explore the effect of mTOR inhibition (everolimus) on several clinical and safety laboratory parameters including plasma lipid levels and blood count. This will be complemented by analysis of inflammatory cell subsets in coronary thrombi and peripheral blood (CD4+ T helper lymphocyte subsets, monocyte subsets).
- Conditions
- Acute Coronary Syndromes
- Being tested
- Everolimus, Placebo
- Keywords
- Acute Coronary Syndromes, ST-Elevation Myocardial Infarction, Infarct size, inflammation, everolimus
- Medical subject headings
- Acute Coronary Syndrome, ST Elevation Myocardial Infarction, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
(d0=7.5 mg, d1=7.5 mg. d2=7.5 mg, d3=5 mg, d4=5mg)
PlaceboDrug
matched placebo tablets manufactured to be identical to verum tablets except content of everolimus
| Study group | Role | What they receive |
|---|---|---|
| Everolimus | Active comparator | Everolimus p.o. for 5 days (d0=7.5 mg, d1=7.5 mg, d2=7.5 mg, d3=5 mg, d4=5mg) Receives: Drug: Everolimus |
| Placebo | Placebo comparator | Placebo comparator with identical composition of tablets except everolimus Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Myocardial infarct size measured by MRI
To assess the effect of mTOR inhibition (everolimus) on myocardial infarct size as measured by MRI (Late Gadolinium Enhancement (LGE) for infarct size (transmurality) at 12-72 h (baseline) and 30 days
Measured: Change from baseline at 30 days
Secondary outcomes (1)
Microvascular obstruction (MVO) measured by MRI
To evaluate microvascular obstruction (MVO) by MRI at 12-72 h (baseline) and 30 days
Measured: Change from baseline at 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2012 (estimated)
- Study start8 Jan 2015
- Primary completion29 Nov 2021
- Study completion29 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acute Coronary SyndromesStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Collaborators
- Swiss National Science Foundation, Novartis
- Responsible party
- Sponsor
- Investigators
- Frank Ruschitzka, Professor, Study director, UniversityHospitalZurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01529554
- Sponsor's protocol ID
- CLEVER-ACS
- Acronym
- CLEVER-ACS
- Status last verified
- Dec 2021
- First submitted
- 3 Feb 2012
- Last updated
- 3 Dec 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Candreva A, Gotschy A MD PhD, Stehli J, Bissig L, Lodi Rizzini M, Chiastra C, Gallo D, Morbiducci U, Klingenberg R, Heg D, Matter CM, Ruschitzka F, Manka R, Stahli BE. Microcirculatory Resistance After Primary Percutaneous Coronary Intervention Predicts Residual Myocardial Damage and Scar Formation. J Am Heart Assoc. 2025 Feb 18;14(4):e036033. doi: 10.1161/JAHA.124.036033. Epub 2025 Feb 8.
PubMed 39921502Stahli BE, Klingenberg R, Heg D, Branca M, Manka R, Kapos I, Muggler O, Denegri A, Kesterke R, Berger F, Stehli J, Candreva A, von Eckardstein A, Carballo D, Hamm C, Landmesser U, Mach F, Moccetti T, Jung C, Kelm M, Munzel T, Pedrazzini G, Raber L, Windecker S, Templin C, Matter CM, Luscher TF, Ruschitzka F. Mammalian Target of Rapamycin Inhibition in Patients With ST-Segment Elevation Myocardial Infarction. J Am Coll Cardiol. 2022 Nov 8;80(19):1802-1814. doi: 10.1016/j.jacc.2022.08.747. Epub 2022 Aug 29.
PubMed 36049557Klingenberg R, Stahli BE, Heg D, Denegri A, Manka R, Kapos I, von Eckardstein A, Carballo D, Hamm CW, Vietheer J, Rolf A, Landmesser U, Mach F, Moccetti T, Jung C, Kelm M, Munzel T, Pedrazzini G, Raber L, Windecker S, Matter CM, Ruschitzka F, Luscher TF. Controlled-Level EVERolimus in Acute Coronary Syndrome (CLEVER-ACS) - A phase II, randomized, double-blind, multi-center, placebo-controlled trial. Am Heart J. 2022 May;247:33-41. doi: 10.1016/j.ahj.2022.01.010. Epub 2022 Jan 28.
PubMed 35092722
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I-II Randomized Prospective Double-blind Multi-center Trial on the Effects of a Short Course of Oral Everolimus on Infarct Size, Left Ventricular Remodeling and Inflammation in Patients With Acute ST-Elevation Myocardial Infarction
- ClinicalTrials.gov ID
- NCT01529554
- Acronym / sponsor ID
- CLEVER-ACS / CLEVER-ACS
- Conditions
- Acute Coronary Syndromes
- Keywords
- Acute Coronary Syndromes, ST-Elevation Myocardial Infarction, Infarct size, inflammation, everolimus
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Collaborators
- Swiss National Science Foundation, Novartis
- Study start
- 8 Jan 2015 (actual)
- Primary completion
- 29 Nov 2021 (actual)
- Study completion
- 29 Nov 2021 (actual)
- First posted
- 9 Feb 2012 (estimated)
- 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.
Acute myocardial infarction (AMI) constitutes the major cause of death in most nations and death rates and morbidity remain substantial in the years thereafter. Inflammation is a hallmark throughout the distinct stages of atherosclerotic lesion formation preceding AMI as well as at the time of plaque rupture and during the post-infarct repair phase. Harnessing its harmful consequences constitutes an attractive therapeutic approach to address this unmet medical need.
The objectives of this study are to evaluate the effects of mTOR inhibition (everolimus) on infarct size, myocardial function and inflammation in patients with ST-Elevation Myocardial Infarction.
The efficacy objectives are:
- (1° endpoint): To assess the effect of mTOR inhibition (everolimus) on myocardial infarct size as change from baseline (12-72 hours after percutaneous coronary intervention) to 30 days follow-up measured by MRI (Late Gadolinium Enhancement (LGE) for transmurality).
- (2° endpoint): To evaluate microvascular obstruction (MVO) as change from baseline (12-72 hours after percutaneous coronary intervention) to 30 days follow-up evaluated by MRI.
- (3° endpoints):
- Change of left ventricular volume from baseline (12-72 hours after percutaneous coronary intervention) to 30 days follow-up measured by MRI.
- Change of biomarkers from time of coronary angiography to 30 days follow-up including a time-course (AUC). Biomarkers comprise hs-TnT, NT-proBNP, hs-CRP, IL-6 and inflammatory biomarkers OPG, sRANKL, OPN and CCN1.
The safety objectives are:
To explore the effect of mTOR inhibition (everolimus) on several clinical and safety laboratory parameters including plasma lipid levels and blood count. This will be complemented by analysis of inflammatory cell subsets in coronary thrombi and peripheral blood (CD4+ T helper lymphocyte subsets, monocyte subsets).
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 |
|---|---|---|
| Everolimus | Active comparator | Drug: EverolimusEverolimus p.o. for 5 days (d0=7.5 mg, d1=7.5 mg, d2=7.5 mg, d3=5 mg, d4=5mg) |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo comparator with identical composition of tablets except everolimus |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Elevation Myocardial Infarction (STEMI) as defined by:
- Chest pain duration of > 10 minutes
- Primary Coronary Intervention (PCI) with drug-eluting stent (DES) within 24 hours of chest pain onset in the occluded culprit artery
- First Myocardial Infarction
- Occluded coronary artery at angiography specifically occlusion of one coronary vessel in the proximal third of either LAD, RCX or RCA, the mid segment of right coronary artery (RCA) or mid segment of a large left anterior descending (LAD) coronary artery, i.e. when the latter reaches the apex.
Key exclusion criteria (10 listed)
- Participation in another drug or stent trial
- Pregnant women or nursing mothers
- Mechanical complication during acute coronary syndrome
- Scheduled PCI for additional lesion within 30 days
- Multivessel disease
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 |
|---|---|---|
| Everolimus(d0=7.5 mg, d1=7.5 mg. d2=7.5 mg, d3=5 mg, d4=5mg) | Drug | Everolimus |
| Placebomatched placebo tablets manufactured to be identical to verum tablets except content of everolimus | Drug | Placebo |
Primary outcome
Myocardial infarct size measured by MRI
Time frame: Change from baseline at 30 days
To assess the effect of mTOR inhibition (everolimus) on myocardial infarct size as measured by MRI (Late Gadolinium Enhancement (LGE) for infarct size (transmurality) at 12-72 h (baseline) and 30 days
1 secondary outcome
Microvascular obstruction (MVO) measured by MRI
Time frame: Change from baseline at 30 days
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 3 Dec 2021.
- Derived from this study: PubMed 39921502Candreva A, Gotschy A MD PhD, Stehli J, Bissig L, Lodi Rizzini M, Chiastra C, Gallo D, Morbiducci U, Klingenberg R, Heg D, Matter CM, Ruschitzka F, Manka R, Stahli BE. Microcirculatory Resistance After Primary Percutaneous Coronary Intervention Predicts Residual Myocardial Damage and Scar Formation. J Am Heart Assoc. 2025 Feb 18;14(4):e036033. doi: 10.1161/JAHA.124.036033. Epub 2025 Feb 8.
- Derived from this study: PubMed 36049557Stahli BE, Klingenberg R, Heg D, Branca M, Manka R, Kapos I, Muggler O, Denegri A, Kesterke R, Berger F, Stehli J, Candreva A, von Eckardstein A, Carballo D, Hamm C, Landmesser U, Mach F, Moccetti T, Jung C, Kelm M, Munzel T, Pedrazzini G, Raber L, Windecker S, Templin C, Matter CM, Luscher TF, Ruschitzka F. Mammalian Target of Rapamycin Inhibition in Patients With ST-Segment Elevation Myocardial Infarction. J Am Coll Cardiol. 2022 Nov 8;80(19):1802-1814. doi: 10.1016/j.jacc.2022.08.747. Epub 2022 Aug 29.
- Derived from this study: PubMed 35092722Klingenberg R, Stahli BE, Heg D, Denegri A, Manka R, Kapos I, von Eckardstein A, Carballo D, Hamm CW, Vietheer J, Rolf A, Landmesser U, Mach F, Moccetti T, Jung C, Kelm M, Munzel T, Pedrazzini G, Raber L, Windecker S, Matter CM, Ruschitzka F, Luscher TF. Controlled-Level EVERolimus in Acute Coronary Syndrome (CLEVER-ACS) - A phase II, randomized, double-blind, multi-center, placebo-controlled trial. Am Heart J. 2022 May;247:33-41. doi: 10.1016/j.ahj.2022.01.010. Epub 2022 Jan 28.
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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.
Frank Ruschitzka, Professor study director
UniversityHospitalZurich
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Everolimus in people with Acute Coronary Syndromes, run by University of Zurich at 8 sites in 2 countries.
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 10 inclusion and 10 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 3 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Germany, 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Myocardial infarct size measured by MRI (time frame: Change from baseline at 30 days). 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 NCT01529554, which also lists 3 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 3 Dec 2021.