Controlled Level EVERolimus in Acute Coronary Syndromes

Acute Coronary Syndromes Clinical Trial

— CLEVER-ACS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01529554
• Other study ID #: CLEVER-ACS
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 8, 2015
• Est. completion date: November 29, 2021

Study information

• Verified date: December 2021
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: November 29, 2021
• Est. primary completion date: November 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Acute Coronary Syndromes
• ST Elevation Myocardial Infarction
• Syndrome

Intervention

Drug:
• Everolimus
(d0=7.5 mg, d1=7.5 mg. d2=7.5 mg, d3=5 mg, d4=5mg)
• Placebo
matched placebo tablets manufactured to be identical to verum tablets except content of everolimus

Locations

Country	Name	City	State
Germany	Kerckhoff-Klinik, Department of Cardiology	Bad Nauheim
Germany	University Hospital Chartié	Berlin
Germany	University Hospital Duesseldorf	Düsseldorf
Germany	University Hospital Mainz	Mainz
Switzerland	University Hospital Bern	Bern
Switzerland	University Hospital Geneva	Geneva
Switzerland	Cardiocentro Ticino	Lugano
Switzerland	University Hospital Zurich	Zurich

Sponsors (3)

Lead Sponsor	Collaborator
University of Zurich	Novartis, Swiss National Science Foundation

Countries where clinical trial is conducted

Germany,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Left ventricular volume measured by MRI	To evaluate left ventricular volume by MRI at 12-72 h (baseline) and 30 days	Change from baseline at 30 days
Other	Biomarkers	To evaluate the changes of left ventricular volume from baseline	Change from baseline at 30 days including time course
Primary	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	Microvascular obstruction (MVO) measured by MRI	To evaluate microvascular obstruction (MVO) by MRI at 12-72 h (baseline) and 30 days	Change from baseline at 30 days