Cyclosporine and Prognosis in Acute Myocardial Infarction (MI) Patients

ST Elevation Acute Myocardial Infarction Clinical Trial

— CIRCUS  

Official title:

Does Cyclosporine ImpRove Clinical oUtcome in ST Elevation Myocardial Infarction Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01502774
• Other study ID #: 2009.559
• Status: Completed
• Phase: Phase 3
• First received: December 28, 2011
• Last updated: February 23, 2018
• Start date: April 2011
• Est. completion date: February 2015

Study information

• Verified date: February 2018
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 970
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction
• ST Elevation Acute Myocardial Infarction
• ST Elevation Myocardial Infarction

Intervention

Drug:
• Injection of Cyclosporin
one single intravenous bolus injection of 2.5 mg/Kg
• Placebo
One single intravenous bolus injection of Placebo

Procedure:
• Echocardiography
1 year after AMI

Locations

Country	Name	City	State
Belgium	Algemeen Ziekenhuis Sint-Jan Brugge	Brugge
Belgium	Chu Charleroi	Charleroi
Belgium	Hôpital universitaire d'Anvers (UZA)	Edegem
Belgium	CHU Mont-Godinne	Yvoir
France	Clinique ESQUIROL - SAINT-HILAIRE	Agen
France	Centre Hospitalier du Pays D'Aix	Aix En Provence
France	Centre Hospitalier Universitaire d'Angers	Angers
France	Centre Hospitalier d'Annecy	Annecy
France	Hôpital Henri Duffaut	Avignon
France	Clinique Lafourcade	Bayonne
France	Centre Hospitalier Universitaire	Brest
France	Hopital Louis Pradel, Hospices Civils de Lyon	Bron cedex
France	CHRU- Hôpital de la Côte de Nacre	Caen
France	Centre Hospitalier General	Chartres
France	CHU - Hôpital Gabriel Montpied	Clermont Ferrand
France	CH de Compiègne	Compiegne
France	CH Henri MONDOR	Creteil
France	Hôpital du Bocage	Dijon
France	Hôpital A. MICHALLON - CHU	Grenoble
France	Centre Hospitalier General	Hagueneau
France	CHRU - Hôpital Cardiologique Calmette	Lille
France	Centre Hospitalier St Luc St Joseph	Lyon
France	Clinique de la Sauvegarde	Lyon
France	Institut Jacques Cartier	Massy
France	CHU Arnaud de Villeneuve	Montpellier
France	Clinique du Millénaire	Montpellier
France	CHU de Mulhouse	Mulhouse
France	Clinique du Diaconat	Mulhouse
France	Hôpital Guillaume et René Laennec	Nantes
France	CHU de Nîmes	Nimes
France	Polyclinique des Fleurs	Ollioules
France	APHP Hôpital Bichat	Paris
France	CH de Pau	PAU
France	Hôpital Haut Lévêque	Pessac
France	Hôpital Claude Galien	Quincy Sous Senart
France	Hôpital Pontchaillou	Rennes
France	Hôpital Charles NICOLLE	Rouen
France	Hôpitaux Universitaires, Nouvel Hôpital Civil	Strasbourg
France	Clinique de l'Ormeau - CCV des Pyrénées	Tarbes
France	CHU de Rangueil	Toulouse
France	CHRU de Tours	Tours
France	Clinique Saint Gatien	Tours
France	Hôpital Brabois - CHU Nancy	Vandoeuvre Les Nancy
France	Clinique du Tonkin	Villeurbanne
Spain	Hospital Universitari Vall d'Hebron	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Countries where clinical trial is conducted

Belgium,  France,  Spain, 

References & Publications (1)

Cung TT, Morel O, Cayla G, Rioufol G, Garcia-Dorado D, Angoulvant D, Bonnefoy-Cudraz E, Guérin 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-Randé JL, Unterseeh T, Le Breton H, Béard 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Combined incidence of [total mortality; hospitalization for heart failure; LV remodeling (increase of LV end-diastolic volume > 15%)]		at 1 year post-AMI
Secondary	Ejection fraction	Functional outcome	at 1 year
Secondary	Left-Ventricular End-Diastolic Volume (LVEDV)	Functional outcome	at 1 year
Secondary	Left-Ventricular End-Systolic Volume (LVESV)	Functional outcome	at 1 year
Secondary	Total mortality		at 1 year
Secondary	Cardiovascular death		at 1 year
Secondary	Heart failure	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	at 1 year
Secondary	Myocardial infarction		at 1 year
Secondary	Unstable angina		at 1 year
Secondary	Stroke		at 1 year
Secondary	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 1 year
Secondary	Infarct size: peak Troponin (T or I)	Explorative outcome. Cardiac prognostic factors.	At admission and at 4 hours (+/- 30 minutes) after study treatment administration
Secondary	Microvascular obstruction (no reflow)	Explorative outcome. Cardiac prognostic factors.	During hospitalization at admission