Does Cyclosporine ImpRove Clinical oUtcome in ST Elevation Myocardial Infarction Patients at 3 Years of Follow-up. CIRCUS II Study (CIRCUS II)

Infarct size is a major determinant of vital prognosis after AMI. We recently reported that cyclosporine A, when administered immediately prior to PCI reperfusion, can significantly reduce infarct size in STEMI patients. The CIRCUS study aimed at determining the impact of cyclosporine on the combined incidence of (death, hospitalization for heart failure, LV remodelling) at one year after AMI. However, many patients may display increased adverse LV remodelling beyond year 1 and develop heart failure thereafter. The present CIRCUS II trial aims at examining the 3-year clinical outcome of all patients recruited in the CIRCUS study.

Study Overview

• Status: Completed
• Conditions: ST Elevation Acute Myocardial Infarction
• Intervention / Treatment: Drug: Injection of Cyclosporin; Procedure: Echocardiography; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 868
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Bron, France
    • Hopital Louis Pradel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All (male and female) patients, aged over 18, without any legal protection measure,
• Having a health coverage,
• Presenting within 12 hours of the onset of chest pain,
• Who have ST segment elevation ≥0.2 mV in two contiguous leads,
• For whom the clinical decision was made to treat with percutaneous coronary intervention (PCI).

And (further inclusion criteria to be confirmed by the admission coronary-angiography):

• The culprit coronary artery has to be the LAD
• The LAD artery has to be occluded (TIMI flow grade 0-1) at the time of admission coronary angiography.
• Preliminary oral informed consent followed by signed informed consent as soon as possible.

Patients undergoing either primary PCI or rescue PCI are eligible for the study. Patients with previous AMI, PCI or coronary artery bypass surgery (CABG) are eligible for the study.

Exclusion Criteria:

• Patients with loss of consciousness or confused
• Patients with cardiogenic shock
• Patients with the left circumflex or the right coronary artery (RCA) as the culprit artery, or with evidence of coronary collaterals to the risk region
• Patients with an opened (TIMI > 1) LAD coronary artery at admission on initial (admission) coronary angiography
• Patients with 1. known hypersensitivity to cyclosporine 2. known hypersensitivity to egg, peanut or Soya-bean proteins 3. known renal insufficiency (either known creatinin clearance < 30 ml/min/1.73m² or current medical care for severe renal insufficiency) 4. known liver insufficiency 5. uncontrolled (treated or untreated) hypertension (> 180/110 mmHg)
• Patients treated with any compound containing Hypericum perforatum (St.-John's-worth) or Stiripentol or Aliskiren or Bosentan or Rosuvastatine
• Female patients currently pregnant or women of childbearing age who were not using contraception (oral diagnosis).
• Patients with any disorder associated with immunological dysfunction more recently than 6 months prior to presentation 1. cancer, lymphoma 2. known positive serology for HIV, or hepatitis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cyclosporin; one single intravenous bolus injection of 2.5 mg/Kg Echocardiography	Drug: Injection of Cyclosporin; one single intravenous bolus injection of 2.5 mg/Kg; Procedure: Echocardiography; 3 years after AMI
Placebo Comparator: Control; one single intravenous bolus injection of Placebo Echocardiography	Procedure: Echocardiography; 3 years after AMI; Drug: Placebo; One single intravenous bolus injection of Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Combined incidence of [total mortality; hospitalization for heart failure; LV remodeling (increase of LV end-diastolic volume > 15%)]	at 12 months post-AMI.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first event [total mortality, hospitalization for heart failure]	Functional outcome	until 3 years post-AMI
Total mortality		at 12 months post-AMI.
Total mortality		at 3 years post-AMI.
Cardiovascular death		at 3 years post-AMI.
Cardiovascular death		at 12 months post-AMI.
Heart failure		at 12 months post-AMI.
Heart failure		at 3 years post-AMI.
Myocardial infarction		at 12 months post-AMI.
Myocardial infarction		at 3 years post-AMI.
Unstable angina		at 12 months post-AMI.
Unstable angina		at 3 years post-AMI.
Stroke		at 12 months post-AMI.
Stroke		at 3 years post-AMI.
Infarct size	Measured by cardiac MRI, only for patients included in participating centers where cardiac MRI is part of the usual post-infarct care	at 12 months post-AMI.
Infarct size	Measured by cardiac MRI, only for patients included in participating centers where cardiac MRI is part of the usual post-infarct care	at 3 years post-AMI.
Quality of life	Assessed by the EQ-5D-3L	at 3 years post-AMI.
Adverse events		at 3 years post-AMI.
Ejection fraction		at 12 months post-AMI
Left-ventricular End-Diastolic Volume (LVEDV)		at 12 months post-AMI
Left-ventricular End-Systolic Volume (LVESV)		at 12 months post-AMI
Infarct size: peak Troponin (T or I)		at 4 hours (+/- 30 minutes) after study treatment administration
Microvascular obstruction	assessed by Magnetic resonance imaging	at 48 hours post-AMI

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Michel OVIZE, Prof, Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2014
• Primary Completion (Actual): June 28, 2017
• Study Completion (Actual): June 28, 2017

Study Registration Dates

• First Submitted: October 13, 2016
• First Submitted That Met QC Criteria: October 13, 2016
• First Posted (Estimate): October 14, 2016

Study Record Updates

• Last Update Posted (Actual): May 22, 2018
• Last Update Submitted That Met QC Criteria: May 17, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: 2013-830

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No