Cyclosporine and Prognosis in Acute Myocardial Infarction (MI) Patients (CIRCUS)

• ClinicalTrials.gov Identifier: NCT01502774
• Recruitment Status: Completed
• First Posted: January 2, 2012
• Last Update Posted: February 26, 2018
• Sponsor: Hospices Civils de Lyon
• Information provided by (Responsible Party): Hospices Civils de Lyon

Tracking Information

• First Submitted Date: December 28, 2011
• First Posted Date: January 2, 2012
• Last Update Posted Date: February 26, 2018
• Study Start Date: April 2011
• Actual Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: April 14, 2015): Combined incidence of [total mortality; hospitalization for heart failure; LV remodeling (increase of LV end-diastolic volume > 15%)] [ Time Frame: at 1 year post-AMI ]
• Original Primary Outcome Measures (submitted: December 29, 2011): Combined incidence of [total mortality; hospitalization for heart failure; LV remodeling (increase of LV end-diastolic volume > 15%)] [ Time Frame: one year post-AMI ]

Current Secondary Outcome Measures (submitted: October 13, 2016)

• Ejection fraction [ Time Frame: at 1 year ]
  Functional outcome
• Left-Ventricular End-Diastolic Volume (LVEDV) [ Time Frame: at 1 year ]
  Functional outcome
• Left-Ventricular End-Systolic Volume (LVESV) [ Time Frame: at 1 year ]
  Functional outcome
• Total mortality [ Time Frame: at 1 year ]
• Cardiovascular death [ Time Frame: at 1 year ]
• Heart failure [ Time Frame: at 1 year ]
  In-hospital worsening of heart failure after reperfusion, or rehospitalization for: a)worsening of a heart failure existing at admission, b)appearance of "new" heart failure
• Myocardial infarction [ Time Frame: at 1 year ]
• Unstable angina [ Time Frame: at 1 year ]
• Stroke [ Time Frame: at 1 year ]
• Infarct size [ Time Frame: at 1 year ]
  Measured by cardiac MRI, only for patients included in participating centers where cardiac MRI is part of the usual post-infarct care
• Infarct size: peak Troponin (T or I) [ Time Frame: At admission and at 4 hours (+/- 30 minutes) after study treatment administration ]
  Explorative outcome. Cardiac prognostic factors.
• Microvascular obstruction (no reflow) [ Time Frame: During hospitalization at admission ]
  Explorative outcome. Cardiac prognostic factors.

Original Secondary Outcome Measures (submitted: December 29, 2011)

• total mortality [ Time Frame: at 1 month and 1 year ]
• cardiovascular death [ Time Frame: at 1 month and 1 year ]
• heart failure [ Time Frame: 12 months after acute MI ]
  in-hospital worsening of heart failure after reperfusion, or re-hospitalization for: 1) worsening of a heart failure existing at admission, 2) appearance of "new" heart failure
• myocardial infarction [ Time Frame: 12 months after acute MI ]
• unstable angina [ Time Frame: 12 months after acute MI ]
• stroke [ Time Frame: 12 months after acute MI ]
• LV remodeling [ Time Frame: 12 months after acute MI ]
• Tolerance to medicinal investigational products [ Time Frame: 12 months after acute MI ]
  Adverse events

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Cyclosporine and Prognosis in Acute Myocardial Infarction (MI) Patients
• Official Title: Does Cyclosporine ImpRove Clinical oUtcome in ST Elevation Myocardial Infarction Patients
• Brief Summary: Infarct size is a major determinant of prognosis after Acute Myocardial Infarction (AMI). The investigators recently reported that cyclosporine A, when administered immediately prior to percutaneous coronary intervention (PCI), can significantly reduce infarct size in STEMI (ST Elevation acute Myocardial Infarction) patients. The objective of the present study is to determine whether cyclosporine can improve STEMI patient clinical outcome. Nine-hundred and seventy two patients with ST elevation MI will be entered into a multicentre, randomized, placebo-controlled, double-blinded study. They will receive one single injection of cyclosporine A (CicloMulsion, verum) or an equivalent volume of placebo prior to reperfusion therapy by PCI. The incidence of the combined endpoint (mortality, hospitalization for heart failure, left ventricular (LV) remodeling) will be assessed at one year and three years after treatment.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: ST Elevation Acute Myocardial Infarction

Intervention

• Drug: Injection of Cyclosporin
  one single intravenous bolus injection of 2.5 mg/Kg
  Other Name: Cyclosporin A (CicloMulsion, verum)
• Drug: Placebo
  One single intravenous bolus injection of Placebo
• Procedure: Echocardiography
  1 year after AMI

Study Arms

• Experimental: Cyclosporin
  Injection of Cyclosporin A : one single intravenous bolus injection of 2.5 mg/Kg Echocardiography
  Interventions:

  • Drug: Injection of Cyclosporin
  • Procedure: Echocardiography
• Placebo Comparator: Control
  one single intravenous bolus injection of Placebo Echocardiography
  Interventions:

  • Drug: Placebo
  • Procedure: Echocardiography

Publications *

• Cung TT, Morel O, Cayla G, Rioufol G, Garcia-Dorado D, Angoulvant D, Bonnefoy-Cudraz E, Guerin P, Elbaz M, Delarche N, Coste P, Vanzetto G, Metge M, Aupetit JF, Jouve B, Motreff P, Tron C, Labeque JN, Steg PG, Cottin Y, Range G, Clerc J, Claeys MJ, Coussement P, Prunier F, Moulin F, Roth O, Belle L, Dubois P, Barragan P, Gilard M, Piot C, Colin P, De Poli F, Morice MC, Ider O, Dubois-Rande JL, Unterseeh T, Le Breton H, Beard T, Blanchard D, Grollier G, Malquarti V, Staat P, Sudre A, Elmer E, Hansson MJ, Bergerot C, Boussaha I, Jossan C, Derumeaux G, Mewton N, Ovize M. Cyclosporine before PCI in Patients with Acute Myocardial Infarction. N Engl J Med. 2015 Sep 10;373(11):1021-31. doi: 10.1056/NEJMoa1505489. Epub 2015 Aug 30.
• Bochaton T, Claeys MJ, Garcia-Dorado D, Mewton N, Bergerot C, Jossan C, Amaz C, Boussaha I, Thibault H, Ovize M. Importance of infarct size versus other variables for clinical outcomes after PPCI in STEMI patients. Basic Res Cardiol. 2019 Dec 12;115(1):4. doi: 10.1007/s00395-019-0764-8.
• Mewton N, Cung TT, Morel O, Cayla G, Bonnefoy-Cudraz E, Rioufol G, Angoulvant D, Guerin P, Elbaz M, Delarche N, Coste P, Vanzetto G, Metge M, Aupetit JF, Jouve B, Motreff P, Tron C, Labeque JN, Steg PG, Cottin Y, Range G, Clerc J, Coussement P, Prunier F, Moulin F, Roth O, Belle L, Dubois P, Barragan P, Gilard M, Piot C, Colin P, Morice MC, Monassier JP, Ider O, Dubois-Rande JL, Unterseeh T, Lebreton H, Beard T, Blanchard D, Grollier G, Malquarti V, Staat P, Sudre A, Hansson MJ, Elmer E, Boussaha I, Jossan C, Torner A, Claeys M, Garcia-Dorado D, Ovize M; CIRCUS Study Investigators. Rationale and design of the Cyclosporine to ImpRove Clinical oUtcome in ST-elevation myocardial infarction patients (the CIRCUS trial). Am Heart J. 2015 Jun;169(6):758-766.e6. doi: 10.1016/j.ahj.2015.02.020. Epub 2015 Mar 13.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 13, 2016): 970
• Original Estimated Enrollment (submitted: December 29, 2011): 972
• Actual Study Completion Date: February 2015
• Actual Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Eligibility criteria (for screening before hospital admission):

1. All (male and female) patients, aged over 18, without any legal protection measure,
2. Having a health coverage,
3. Presenting within 12 hours of the onset of chest pain,
4. Who have ST segment elevation ≥0.2 mV in two contiguous leads,

5. 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):

6. The culprit coronary artery has to be the LAD
7. The LAD artery has to be occluded (TIMI flow grade 0-1) at the time of admission coronary angiography.
8. 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:

1. Patients with loss of consciousness or confused
2. Patients with cardiogenic shock
3. 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
4. Patients with an opened (TIMI > 1) LAD coronary artery at admission on initial (admission) coronary angiography
5. Patients with 5.2. known hypersensitivity to cyclosporine 5.3. known hypersensitivity to egg, peanut or Soya-bean proteins 5.4. known renal insufficiency (either known creatinin clearance < 30 ml/min/1.73m² or current medical care for severe renal insufficiency) 5.5. known liver insufficiency 5.6. uncontrolled (treated or untreated) hypertension (> 180/110 mmHg)
6. Patients treated with any compound containing Hypericum perforatum (St.-John's-worth) or Stiripentol or Aliskiren or Bosentan or Rosuvastatine
7. Female patients currently pregnant or women of childbearing age who were not using contraception (oral diagnosis).
8. Patients with any disorder associated with immunological dysfunction more recently than 6 months prior to presentation 8.2. cancer, lymphoma 8.3. known positive serology for HIV, or hepatitis

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, France, Spain

Administrative Information

• NCT Number: NCT01502774
• Other Study ID Numbers: 2009.559
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hospices Civils de Lyon
• Original Responsible Party: Same as current
• Current Study Sponsor: Hospices Civils de Lyon
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Michel OVIZE, MD, Prof; Hospices Civils de Lyon

• PRS Account: Hospices Civils de Lyon
• Verification Date: February 2018