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Cyclosporine in Acute Myocardial Infarction Complicated by Cardiogenic Shock

Phase 2
Withdrawn
Conditions
Acute Myocardial Infarction
Interventions
Drug: Single bolus of cyclosporine A (CicloMulsion®, Neurovive)
Drug: Single bolus of Placebo of CicloMulsion® (Neurovive).
Registration Number
NCT01901471
Lead Sponsor
Hospices Civils de Lyon
Brief Summary

The size of the acute myocardial infarction (AMI) is related to ischemia and injury induced by tissue reperfusion. These reperfusion's injuries can be reduced by injection of cyclosporin A (CsA) at the time of reperfusion. This post-conditioning reduces the final infarct size 20 to 40%. This has been demonstrated in STEMI patients non-complicated by cardiogenic shock. Early revascularization in the AMI complicated by cardiogenic shock improves short-term and long term survival by reducing the size of the myocardial infarction. The hypothesis of this study is that the administration of Cyclosporin A to these patients, in addition to mechanical reperfusion, is likely to reduce the severity of the multi-organ failure associated with the cardiogenic shock and improve clinical outcome.

Detailed Description

Not available

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
Inclusion Criteria
  • Patients ( male or female), aged over 18, without any legal protection measure
  • Having a health coverage
  • Presenting within 12 hours of the onset of chest pain, with a ST segment elevation or non ST elevation and for whom the clinical decision was made to treat with percutaneous coronary intervention (PCI) primary or rescue
  • Occlusion of culprit coronary artery (TIMI flow grade = 0 or 1) at the time of admission in the catheterism laboratory
  • Patient presenting a cardiogenic shock defined by a SBP<90mmhg for a period over 30 minutes and do not answering to a test of vascular charge associated with signs peripheral hypoperfusion (cold extremities, cyanosis, oliguria with urine output <50 ml/h or alteration of higher mental functions).
  • Clear information is delivered to the patient or a legal representative if present and preliminary oral consent obtained, followed by obtaining written consent signed as soon as possible, in accordance with ICH.

NB: 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
  • TIMI flow grade >1
  • Patients in cardiac arrest
  • Patients with mechanical complication of myocardial infarction at admission (septal, broken pillar cracking or myocardial rupture, tamponade).
  • Patients with other causes of hemodynamic shock: hemorrhagic, septic or anaphylactic.
  • Patients with known hypersensitivity to cyclosporine, hypersensitivity to egg, peanut or Soya-bean proteins
  • Renal insufficiency (either known creatinine clearance < 30 ml/min/1.73m² or current medical care for severe renal insufficiency)
  • Patients treated with any compound containing Hypericum perforatum (St. John's Wort) 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, cancer, lymphoma, known positive serology for HIV, or hepatitis
  • Participation to another clinical trial

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CsA GroupSingle bolus of cyclosporine A (CicloMulsion®, Neurovive)-
Placebo groupSingle bolus of Placebo of CicloMulsion® (Neurovive).-
Primary Outcome Measures
NameTimeMethod
multiorgan failure evaluated by the SOFA scoreAt 24 hours after admission

The SOFA clinico-biological score takes into account the respiratory status, cardiac, hepatic, renal, neurological and the biological parameters of coagulation of the patient. This score is spread from 0 to 24 points.

Secondary Outcome Measures
NameTimeMethod
multiorgan failure by SOFA scoreAt 48 hours after admission

The SOFA clinico-biological score takes into account the respiratory status, cardiac, hepatic, renal,neurological and the biological parameters of coagulation of the patient. This score is spread from 0 to 24 points.

multiorgan failure by SAPSII scoresAt 24 hours and at 48 hours

The SAPSII score takes into account the hemodynamic, clinical, biological status of the patient. The parameters are : history of patient (type of admission, chronic disease, age), clinical parameters as systolic pressure measurement, heart rate, temperature, urine output of 24 hours and biological parameters as measurement of blood count white, serum total bilirubin, serum urea, serum sodium, serum potassium and bicarbonate level serum. pressure measurement arterial oxygen in arterial blood gases. This score is spread from 0 to 163 points.

Cardiac output (CO)At 24 hours after inclusion

The hemodynamic changes will be estimated by measuring the cardiac output (CO) obtained by echocardiography.

Reduction of infarct sizeduring the first 72 hours after admission

evaluation of the under curve area of serum creatinin kinase (CK) measured during the 72 first hours after admission (12 blood sampling).

Reduction of cardiovascular morbidity and mortalityat 1 month

The incidence that occurred in one month (D30) of the following clinical criteria will be collected: death, ventricular fibrillation or ventricular tachycardia requiring electrical cardioversion, placed under mechanical cardiac support (other than against drive-by intra-aortic balloon) , reinfarction, hospitalization for heart failure.

Reduction of Left ventricular remodelingat 1 month

Left ventricular remodeling will be assessed at 1 month among surviving patients by measurement of left ventricular end-diastolic volume by transthoracic echocardiography

Trial Locations

Locations (18)

Hopital Guillaume Et Rene Laennec

🇫🇷

Nantes, France

CH Pays d'Aix

🇫🇷

Aix-en-Provence, France

Chu de Nimes

🇫🇷

Nimes, France

Chu de Rangueil

🇫🇷

Toulouse, France

Chu de Bordeaux

🇫🇷

Pessac, France

CHU Hopital Cardiologique Louis Pradel

🇫🇷

Bron, France

Chu de Nancy Brabois

🇫🇷

Vandoeuvre Les Nancy, France

Hôpital Gabriel Montpied

🇫🇷

Clermont-ferrand, France

Chu Hopital A Michallon

🇫🇷

Grenoble, France

Nouvel Hôpital Civil

🇫🇷

Strasbourg, France

Clinique de La Fourcade

🇫🇷

Bayonne, France

Centre Hospitalier de Pau

🇫🇷

PAU, France

Chu Arnaud de Villeneuve

🇫🇷

Montpellier, France

Hopital St Luc St Joseph

🇫🇷

Lyon, France

Chu Hopital Du Bocage

🇫🇷

Dijon, France

Hopital Charles Nicolle

🇫🇷

Rouen, France

Aphp Hopital Bichat

🇫🇷

Paris, France

Chru de Tours

🇫🇷

Tours, France

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