NCT01529554

Brief 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 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.(1° endpoint):
  2. 2.(2° endpoint):
  3. 3.(3° endpoints):
  4. 4.Change of left ventricular volume from baseline (12-72 hours after percutaneous coronary intervention) to 30 days follow-up measured by MRI.
  5. 5.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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
150

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jan 2015

Longer than P75 for phase_1

Geographic Reach
2 countries

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 3, 2012

Completed
6 days until next milestone

First Posted

Study publicly available on registry

February 9, 2012

Completed
2.9 years until next milestone

Study Start

First participant enrolled

January 8, 2015

Completed
6.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 29, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 29, 2021

Completed
Last Updated

December 3, 2021

Status Verified

December 1, 2021

Enrollment Period

6.9 years

First QC Date

February 3, 2012

Last Update Submit

December 2, 2021

Conditions

Acute Coronary Syndromes

Keywords

Acute Coronary SyndromesST-Elevation Myocardial InfarctionInfarct sizeinflammationeverolimus

Outcome Measures

Primary Outcomes (1)

  • 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

    Change from baseline at 30 days

Secondary Outcomes (1)

  • Microvascular obstruction (MVO) measured by MRI

    Change from baseline at 30 days

Other Outcomes (2)

  • Left ventricular volume measured by MRI

    Change from baseline at 30 days

  • Biomarkers

    Change from baseline at 30 days including time course

Study Arms (2)

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)

Drug: Everolimus

Placebo

PLACEBO COMPARATOR

Placebo comparator with identical composition of tablets except everolimus

Drug: Placebo

Interventions

EverolimusDRUG

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

Everolimus
PlaceboDRUG

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

Placebo

Eligibility Criteria

Age18 Years - 90 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • 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

You may not qualify if:

  • 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
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Kerckhoff-Klinik, Department of Cardiology

Bad Nauheim, Germany

Location

University Hospital Chartié

Berlin, Germany

Location

University Hospital Duesseldorf

Düsseldorf, Germany

Location

University Hospital Mainz

Mainz, Germany

Location

University Hospital Bern

Bern, Switzerland

Location

University Hospital Geneva

Geneva, Switzerland

Location

Cardiocentro Ticino

Lugano, Switzerland

Location

University Hospital Zurich

Zurich, Switzerland

Location

Related Publications (3)

  • 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.

    PMID: 39921502DERIVED

  • 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.

    PMID: 36049557DERIVED

  • 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.

    PMID: 35092722DERIVED

MeSH Terms

Conditions

Acute Coronary SyndromeST Elevation Myocardial InfarctionInflammation

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Myocardial IschemiaHeart DiseasesCardiovascular DiseasesVascular DiseasesMyocardial InfarctionInfarctionIschemiaPathologic ProcessesPathological Conditions, Signs and SymptomsNecrosis

Intervention Hierarchy (Ancestors)

SirolimusMacrolidesLactonesOrganic Chemicals

Study Officials

  • Frank Ruschitzka, Professor

    UniversityHospitalZurich

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 3, 2012

First Posted

February 9, 2012

Study Start

January 8, 2015

Primary Completion

November 29, 2021

Study Completion

November 29, 2021

Last Updated

December 3, 2021

Record last verified: 2021-12

Locations

CH(4)DE(4)