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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon
ClinicalTrials.gov Identifier:
NCT01502774
First received: December 28, 2011
Last updated: April 22, 2015
Last verified: April 2015
  Purpose

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.


Condition Intervention Phase
ST Elevation Acute Myocardial Infarction
Drug: Injection of Cyclosporin
Drug: Placebo
Procedure: Echocardiography
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Does Cyclosporine ImpRove Clinical oUtcome in ST Elevation Myocardial Infarction Patients

Resource links provided by NLM:


Further study details as provided by Hospices Civils de Lyon:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Ejection fraction [ Time Frame: at 1 year ] [ Designated as safety issue: No ]
    Functional outcome

  • Left-Ventricular End-Diastolic Volume (LVEDV) [ Time Frame: at 1 year ] [ Designated as safety issue: No ]
    Functional outcome

  • Left-Ventricular End-Systolic Volume (LVESV) [ Time Frame: at 1 year ] [ Designated as safety issue: No ]
    Functional outcome

  • Time to first event [total mortality, hospitalization for heart failure] [ Time Frame: until 3 years post-AMI ] [ Designated as safety issue: No ]
    Functional outcome

  • Total mortality [ Time Frame: at 1 year ] [ Designated as safety issue: No ]
  • Total mortality [ Time Frame: at 3 years ] [ Designated as safety issue: No ]
  • Cardiovascular death [ Time Frame: at 1 year ] [ Designated as safety issue: No ]
  • Cardiovascular death [ Time Frame: at 3 years ] [ Designated as safety issue: No ]
  • Heart failure [ Time Frame: at 1 year ] [ Designated as safety issue: No ]
    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

  • Heart failure [ Time Frame: at 3 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Myocardial infarction [ Time Frame: at 3 years ] [ Designated as safety issue: No ]
  • Unstable angina [ Time Frame: at 1 year ] [ Designated as safety issue: No ]
  • Unstable angina [ Time Frame: at 3 years ] [ Designated as safety issue: No ]
  • Stroke [ Time Frame: at 1 year ] [ Designated as safety issue: No ]
  • Stroke [ Time Frame: at 3 years ] [ Designated as safety issue: No ]
  • Infarct size [ Time Frame: at 1 year ] [ Designated as safety issue: No ]
    Measured by cardiac MRI, only for patients included in participating centers where cardiac MRI is part of the usual post-infarct care

  • Infarct size [ Time Frame: at 3 years ] [ Designated as safety issue: No ]
    Measured by cardiac MRI, only for patients included in participating centers where cardiac MRI is part of the usual post-infarct care

  • Quality of life [ Time Frame: at 3 years ] [ Designated as safety issue: No ]
  • Tolerance to medicinal investigational products [ Time Frame: until 3 years ] [ Designated as safety issue: Yes ]
    With adverse events and serious adverse events described by SOC following MedDRA classification

  • Predictive value of LVEDV [ Time Frame: at 3 years ] [ Designated as safety issue: No ]
    Explorative outcome. Major adverse cardiac events in the 2 years follow-up period after the measurement of LVEDV at 1 year months.

  • Infarct size: peak Troponin (T or I) [ Time Frame: At admission and at 4 hours (+/- 30 minutes) after study treatment administration ] [ Designated as safety issue: No ]
    Explorative outcome. Cardiac prognostic factors.

  • Microvascular obstruction (no reflow) [ Time Frame: During hospitalization at admission ] [ Designated as safety issue: No ]
    Explorative outcome. Cardiac prognostic factors.


Estimated Enrollment: 972
Study Start Date: April 2011
Estimated Study Completion Date: February 2017
Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cyclosporin
Injection of Cyclosporin A : 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
Other Name: Cyclosporin A (CicloMulsion, verum)
Procedure: Echocardiography
1 year and 3 years after AMI
Placebo Comparator: Control
one single intravenous bolus injection of Placebo Echocardiography
Drug: Placebo
One single intravenous bolus injection of Placebo
Procedure: Echocardiography
1 year and 3 years after AMI

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01502774

Locations
France
Clinique ESQUIROL - SAINT-HILAIRE
Agen, France, 47000
Centre Hospitalier du Pays D'Aix
Aix En Provence, France, 13616
Centre Hospitalier Universitaire d'Angers
Angers, France, 49033
Centre Hospitalier d'Annecy
Annecy, France, 74011
Hôpital Henri Duffaut
Avignon, France, 84000
Clinique Lafourcade
Bayonne, France, 64100
Centre Hospitalier Universitaire
Brest, France, 29609
Hopital Louis Pradel, Hospices Civils de Lyon
Bron cedex, France, 69677
CHRU- Hôpital de la Côte de Nacre
Caen, France, 14033
Centre Hospitalier General
Chartres, France, 28018
CHU - Hôpital Gabriel Montpied
Clermont Ferrand, France, 63003
CH de Compiègne
Compiegne, France, 60321
CH Henri MONDOR
Creteil, France, 94010
Hôpital du Bocage
Dijon, France, 21034
Hôpital A. MICHALLON - CHU
Grenoble, France, 38043
Centre Hospitalier General
Hagueneau, France, 67504
CHRU - Hôpital Cardiologique Calmette
Lille, France
Centre Hospitalier St Luc St Joseph
Lyon, France, 69365
Clinique de la Sauvegarde
Lyon, France, 69009
Institut Jacques Cartier
Massy, France, 91300
CHU Arnaud de Villeneuve
Montpellier, France, 34295
Clinique du Millénaire
Montpellier, France, 34960
CHU de Mulhouse
Mulhouse, France, 68100
Clinique du Diaconat
Mulhouse, France, 69607
Hôpital Guillaume et René Laennec
Nantes, France, 44093
CHU de Nîmes
Nimes, France, 30029
Polyclinique des Fleurs
Ollioules, France, 83192
APHP Hôpital Bichat
Paris, France, 75018
CH de Pau
PAU, France, 64011
Hôpital Haut Lévêque
Pessac, France, 33604
Hôpital Claude Galien
Quincy Sous Senart, France, 91480
Hôpital Pontchaillou
Rennes, France, 35003
Hôpital Charles NICOLLE
Rouen, France, 76031
Hôpitaux Universitaires, Nouvel Hôpital Civil
Strasbourg, France, 67091
Clinique de l'Ormeau - CCV des Pyrénées
Tarbes, France, 65000
CHU de Rangueil
Toulouse, France, 31043
CHRU de Tours
Tours, France, 37044
Clinique Saint Gatien
Tours, France, 37042
Hôpital Brabois - CHU Nancy
Vandoeuvre Les Nancy, France, 54511
Clinique du Tonkin
Villeurbanne, France, 69100
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
Principal Investigator: Michel OVIZE, MD, Prof Hospices Civils de Lyon
  More Information

No publications provided

Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT01502774     History of Changes
Other Study ID Numbers: 2009.559
Study First Received: December 28, 2011
Last Updated: April 22, 2015
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Hospices Civils de Lyon:
STEMI
cyclosporine
reperfusion injury

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Cardiovascular Diseases
Heart Diseases
Ischemia
Myocardial Ischemia
Necrosis
Pathologic Processes
Vascular Diseases
Cyclosporine
Cyclosporins
Anti-Infective Agents
Antifungal Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on May 03, 2015