Cyclosporine and Prognosis in Acute Myocardial Infarction (MI) Patients

NCT01502774 | Completed Phase 3 DMC

• 1 other identifier: 2009.559
• Study Type: interventional
• Target: 970
• Locations: 3 countries
• Sites: 45

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.

Conditions

ST Elevation Acute Myocardial Infarction

Keywords

STEMI; cyclosporine; reperfusion injury

Outcome Measures

Primary Outcomes (1)

• Combined incidence of [total mortality; hospitalization for heart failure; LV remodeling (increase of LV end-diastolic volume > 15%)]

  at 1 year post-AMI

Secondary Outcomes (12)

• Ejection fraction

  at 1 year

• Left-Ventricular End-Diastolic Volume (LVEDV)

  at 1 year

• Left-Ventricular End-Systolic Volume (LVESV)

  at 1 year

• Total mortality

  at 1 year

• Cardiovascular death

  at 1 year

Study Arms (2)

Cyclosporin

EXPERIMENTAL

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

Drug: Injection of Cyclosporin; Procedure: Echocardiography

Control

PLACEBO COMPARATOR

one single intravenous bolus injection of Placebo Echocardiography

Drug: Placebo; Procedure: Echocardiography

Interventions

Injection of Cyclosporin DRUG

one single intravenous bolus injection of 2.5 mg/Kg

Also known as: Cyclosporin A (CicloMulsion, verum)

Cyclosporin

Placebo DRUG

One single intravenous bolus injection of Placebo

Control

Echocardiography PROCEDURE

1 year after AMI

Control; Cyclosporin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligibility criteria (for screening before hospital admission):
• 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).
• 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.

You may not qualify if:

• 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 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)
• 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 8.2. cancer, lymphoma 8.3. known positive serology for HIV, or hepatitis

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (45)

Algemeen Ziekenhuis Sint-Jan Brugge

Bruges, 8000, Belgium

Location

Chu Charleroi

Charleroi, 6000, Belgium

Location

Hôpital universitaire d'Anvers (UZA)

Edegem, 2650, Belgium

Location

CHU Mont-Godinne

Yvoir, 5530, Belgium

Location

Clinique ESQUIROL - SAINT-HILAIRE

Agen, 47000, France

Location

Centre Hospitalier du Pays D'Aix

Aix-en-Provence, 13616, France

Location

Centre Hospitalier Universitaire d'Angers

Angers, 49033, France

Location

Centre Hospitalier d'Annecy

Annecy, 74011, France

Location

Hôpital Henri Duffaut

Avignon, 84000, France

Location

Clinique Lafourcade

Bayonne, 64100, France

Location

Centre Hospitalier Universitaire

Brest, 29609, France

Location

Hopital Louis Pradel, Hospices Civils de Lyon

Bron, 69677, France

Location

CHRU- Hôpital de la Côte de Nacre

Caen, 14033, France

Location

Centre Hospitalier General

Chartres, 28018, France

Location

CHU - Hôpital Gabriel Montpied

Clermont-Ferrand, 63003, France

Location

CH de Compiègne

Compiègne, 60321, France

Location

CH Henri MONDOR

Créteil, 94010, France

Location

Hôpital du Bocage

Dijon, 21034, France

Location

Hôpital A. MICHALLON - CHU

Grenoble, 38043, France

Location

Centre Hospitalier General

Haguenau, 67504, France

Location

CHRU - Hôpital Cardiologique Calmette

Lille, France

Location

Clinique de la Sauvegarde

Lyon, 69009, France

Location

Centre Hospitalier St Luc St Joseph

Lyon, 69365, France

Location

Institut Jacques Cartier

Massy, 91300, France

Location

CHU Arnaud de Villeneuve

Montpellier, 34295, France

Location

Clinique du Millénaire

Montpellier, 34960, France

Location

CHU de Mulhouse

Mulhouse, 68100, France

Location

Clinique du Diaconat

Mulhouse, 69607, France

Location

Hôpital Guillaume et René Laennec

Nantes, 44093, France

Location

CHU de Nîmes

Nîmes, 30029, France

Location

Polyclinique des Fleurs

Ollioules, 83192, France

Location

APHP Hôpital Bichat

Paris, 75018, France

Location

CH de Pau

Pau, 64011, France

Location

Hôpital Haut Lévêque

Pessac, 33604, France

Location

Hôpital Claude Galien

Quincy-sous-Sénart, 91480, France

Location

Hôpital Pontchaillou

Rennes, 35003, France

Location

Hôpital Charles NICOLLE

Rouen, 76031, France

Location

Hôpitaux Universitaires, Nouvel Hôpital Civil

Strasbourg, 67091, France

Location

Clinique de l'Ormeau - CCV des Pyrénées

Tarbes, 65000, France

Location

CHU de Rangueil

Toulouse, 31043, France

Location

Clinique Saint Gatien

Tours, 37042, France

Location

CHRU de Tours

Tours, 37044, France

Location

Hôpital Brabois - CHU Nancy

Vandœuvre-lès-Nancy, 54511, France

Location

Clinique du Tonkin

Villeurbanne, 69100, France

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Related Publications (3)

• 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.

  PMID: 26321103 RESULT

• 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.

  PMID: 31832789 DERIVED

• 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.

  PMID: 26027612 DERIVED

MeSH Terms

Conditions

ST Elevation Myocardial Infarction; Reperfusion Injury

Interventions

Cyclosporine

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Postoperative Complications

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Michel OVIZE, MD, Prof

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2011
• First Posted: January 2, 2012
• Study Start: April 1, 2011
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: September 4, 2025

Record last verified: 2025-08

Locations

BE (4); FR (40); ES (1)