Controlled Level EVERolimus in Acute Coronary Syndromes

NCT ID: NCT01529554

Last Updated: 2021-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-01-08

Study Completion Date

2021-11-29

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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. (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. (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. (3° endpoints):

1. Change of left ventricular volume from baseline (12-72 hours after percutaneous coronary intervention) to 30 days follow-up measured by MRI.
2. 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).

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Acute Coronary Syndromes

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Acute Coronary Syndromes ST-Elevation Myocardial Infarction Infarct size inflammation everolimus

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Everolimus

Everolimus p.o. for 5 days (d0=7.5 mg, d1=7.5 mg, d2=7.5 mg, d3=5 mg, d4=5mg)

Group Type ACTIVE_COMPARATOR

Everolimus

Intervention Type DRUG

(d0=7.5 mg, d1=7.5 mg. d2=7.5 mg, d3=5 mg, d4=5mg)

Placebo

Placebo comparator with identical composition of tablets except everolimus

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

matched placebo tablets manufactured to be identical to verum tablets except content of everolimus

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Everolimus

(d0=7.5 mg, d1=7.5 mg. d2=7.5 mg, d3=5 mg, d4=5mg)

Intervention Type DRUG

Placebo

matched placebo tablets manufactured to be identical to verum tablets except content of everolimus

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. 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
2. Chest pain duration of \> 10 minutes
3. Primary Coronary Intervention (PCI) with drug-eluting stent (DES) within 24 hours of chest pain onset in the occluded culprit artery
4. First Myocardial Infarction
5. 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.
6. Male and female patients 18 years to 90 years of age
7. Signed informed consent

Exclusion Criteria

1. Participation in another drug or stent trial
2. Pregnant women or nursing mothers
3. Mechanical complication during acute coronary syndrome
4. Scheduled PCI for additional lesion within 30 days
5. Multivessel disease
6. Major elective surgery planned in trial period
7. Malignancy (unless healed or remission \> 5 years)
8. Chronic infection (HIV, Tbc, empyema)
9. Severely compromised renal function (GFR\< 30 ml/min)
10. Positive PCR Test for SARS-CoV-2 and/or at least one positive answer to questions regarding symptoms/contact related to COVID-19.
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Swiss National Science Foundation

OTHER

Sponsor Role collaborator

Novartis

INDUSTRY

Sponsor Role collaborator

University of Zurich

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Frank Ruschitzka, Professor

Role: STUDY_DIRECTOR

UniversityHospitalZurich

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Kerckhoff-Klinik, Department of Cardiology

Bad Nauheim, , Germany

Site Status

University Hospital Chartié

Berlin, , Germany

Site Status

University Hospital Duesseldorf

Düsseldorf, , Germany

Site Status

University Hospital Mainz

Mainz, , Germany

Site Status

University Hospital Bern

Bern, , Switzerland

Site Status

University Hospital Geneva

Geneva, , Switzerland

Site Status

Cardiocentro Ticino

Lugano, , Switzerland

Site Status

University Hospital Zurich

Zurich, , Switzerland

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Germany Switzerland

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 39921502 (View on PubMed)

Stahli 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.

Reference Type DERIVED
PMID: 36049557 (View on PubMed)

Klingenberg 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.

Reference Type DERIVED
PMID: 35092722 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

CLEVER-ACS

Identifier Type: -

Identifier Source: org_study_id