Clinical trial NCT01502774: Cyclosporine and Prognosis in Acute Myocardial Infarction (MI) Patients
Official title: Does Cyclosporine ImpRove Clinical oUtcome in ST Elevation Myocardial Infarction Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: ST Elevation Acute Myocardial Infarction
Keywords: STEMI
cyclosporine
reperfusion injury
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2012-01-02
Enrollment: 970
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Combined incidence of [total mortality; hospitalization for heart failure; LV remodeling (increase of LV end-diastolic volume > 15%)]
timeFrame: at 1 year post-AMI
Secondary outcomes:
measure: Ejection fraction
timeFrame: at 1 year
measure: Left-Ventricular End-Diastolic Volume (LVEDV)
timeFrame: at 1 year
measure: Left-Ventricular End-Systolic Volume (LVESV)
timeFrame: at 1 year
measure: Total mortality
timeFrame: at 1 year
measure: Cardiovascular death
timeFrame: at 1 year
measure: Heart failure
timeFrame: at 1 year
measure: Myocardial infarction
timeFrame: at 1 year
measure: Unstable angina
timeFrame: at 1 year
measure: Stroke
timeFrame: at 1 year
measure: Infarct size
timeFrame: at 1 year
measure: Infarct size: peak Troponin (T or I)
timeFrame: At admission and at 4 hours (+/- 30 minutes) after study treatment administration
measure: Microvascular obstruction (no reflow)
timeFrame: During hospitalization at admission
Other outcomes:
Locations:
city: Brugge
country: Belgium
facility: Algemeen Ziekenhuis Sint-Jan Brugge
city: Charleroi
country: Belgium
facility: Chu Charleroi
city: Edegem
country: Belgium
facility: Hôpital universitaire d'Anvers (UZA)
city: Yvoir
country: Belgium
facility: CHU Mont-Godinne
city: Agen
country: France
facility: Clinique ESQUIROL - SAINT-HILAIRE
city: Aix En Provence
country: France
facility: Centre Hospitalier du Pays D'Aix
city: Angers
country: France
facility: Centre Hospitalier Universitaire d'Angers
city: Annecy
country: France
facility: Centre Hospitalier d'Annecy
city: Avignon
country: France
facility: Hôpital Henri Duffaut
city: Bayonne
country: France
facility: Clinique Lafourcade
city: Brest
country: France
facility: Centre Hospitalier Universitaire
city: Bron cedex
country: France
facility: Hopital Louis Pradel, Hospices Civils de Lyon
city: Caen
country: France
facility: CHRU- Hôpital de la Côte de Nacre
city: Chartres
country: France
facility: Centre Hospitalier General
city: Clermont Ferrand
country: France
facility: CHU - Hôpital Gabriel Montpied
city: Compiegne
country: France
facility: CH de Compiègne
city: Creteil
country: France
facility: CH Henri MONDOR
city: Dijon
country: France
facility: Hôpital du Bocage
city: Grenoble
country: France
facility: Hôpital A. MICHALLON - CHU
city: Hagueneau
country: France
facility: Centre Hospitalier General
city: Lille
country: France
facility: CHRU - Hôpital Cardiologique Calmette
city: Lyon
country: France
facility: Clinique de la Sauvegarde
city: Lyon
country: France
facility: Centre Hospitalier St Luc St Joseph
city: Massy
country: France
facility: Institut Jacques Cartier
city: Montpellier
country: France
facility: CHU Arnaud de Villeneuve
city: Montpellier
country: France
facility: Clinique du Millénaire
city: Mulhouse
country: France
facility: CHU de Mulhouse
city: Mulhouse
country: France
facility: Clinique du Diaconat
city: Nantes
country: France
facility: Hôpital Guillaume et René Laennec
city: Nimes
country: France
facility: CHU de Nîmes
city: Ollioules
country: France
facility: Polyclinique des Fleurs
city: Paris
country: France
facility: APHP Hôpital Bichat
city: PAU
country: France
facility: CH de Pau
city: Pessac
country: France
facility: Hôpital Haut Lévêque
city: Quincy Sous Senart
country: France
facility: Hôpital Claude Galien
city: Rennes
country: France
facility: Hôpital Pontchaillou
city: Rouen
country: France
facility: Hôpital Charles NICOLLE
city: Strasbourg
country: France
facility: Hôpitaux Universitaires, Nouvel Hôpital Civil
city: Tarbes
country: France
facility: Clinique de l'Ormeau - CCV des Pyrénées
city: Toulouse
country: France
facility: CHU de Rangueil
city: Tours
country: France
facility: Clinique Saint Gatien
city: Tours
country: France
facility: CHRU de Tours
city: Vandoeuvre Les Nancy
country: France
facility: Hôpital Brabois - CHU Nancy
city: Villeurbanne
country: France
facility: Clinique du Tonkin
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
Study officials:
affiliation: Hospices Civils de Lyon
name: Michel OVIZE, MD, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.