Cyclosporine in Acute Myocardial Infarction Complicated by Cardiogenic Shock

NCT ID: NCT01901471

Last Updated: 2016-03-16

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2015-10-31

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.

Conditions

Acute Myocardial Infarction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

CsA Group

Group Type: EXPERIMENTAL

Single bolus of cyclosporine A (CicloMulsion®, Neurovive)

Intervention Type: DRUG

The investigational medicinal product is cyclosporine A (CicloMulsion®, Neurovive).

Cyclosporine A is an immunosuppressive treatment usually used in the prevention of acute rejection after organ transplant, including cardiac transplantation. Usual dosages in organ transplantation are about 2.5 mg / kg per day in 2 doses.

CicloMulsion® is ready-to-use lipid emulsions, i.e. do not need any step of preparation or dilution.

Production blinded labelling, packaging and delivering the study drugs in every participating centre of the trial will be performed by a company following European Union's Good Manufacturing Practice.

CicloMulsion® 5mg/ml is provided in colourless glass bottles sealed with a rubber stopper, containing a nominal fill volume of 50 ml.

The study treatment will be directly taken into the vial and injected via a catheter positioned within an antecubital vein. The injection will be performed slowly over 2 to 3 minutes.

Placebo group

Group Type: PLACEBO_COMPARATOR

Single bolus of Placebo of CicloMulsion® (Neurovive).

Intervention Type: DRUG

The matching placebo of CicloMulsion® (Neurovive) is composed with refined Soya-bean oil, medium-chain triglycerides, egg lecithin, water-free glycerol, sodium oleate, sodium hydroxide, water injection. The qualitative composition of CicloMulsion® and its placebo only differ in the presence or absence of Cyclosporine A, so the final emulsions will be visually indistinguishable.

The placebo use here is ready-to-use lipid emulsions, i.e. do not need any step of preparation or dilution.

The placebo is provided in colourless glass bottles sealed with a rubber stopper, containing a nominal fill volume of 50 ml.

The study treatment will be directly taken into the vial and injected via a catheter positioned within an antecubital vein. The injection will be performed slowly over 2 to 3 minutes.

Interventions

Single bolus of Placebo of CicloMulsion® (Neurovive).

The matching placebo of CicloMulsion® (Neurovive) is composed with refined Soya-bean oil, medium-chain triglycerides, egg lecithin, water-free glycerol, sodium oleate, sodium hydroxide, water injection. The qualitative composition of CicloMulsion® and its placebo only differ in the presence or absence of Cyclosporine A, so the final emulsions will be visually indistinguishable.

The placebo use here is ready-to-use lipid emulsions, i.e. do not need any step of preparation or dilution.

The placebo is provided in colourless glass bottles sealed with a rubber stopper, containing a nominal fill volume of 50 ml.

The study treatment will be directly taken into the vial and injected via a catheter positioned within an antecubital vein. The injection will be performed slowly over 2 to 3 minutes.

Intervention Type: DRUG

Single bolus of cyclosporine A (CicloMulsion®, Neurovive)

The investigational medicinal product is cyclosporine A (CicloMulsion®, Neurovive).

Cyclosporine A is an immunosuppressive treatment usually used in the prevention of acute rejection after organ transplant, including cardiac transplantation. Usual dosages in organ transplantation are about 2.5 mg / kg per day in 2 doses.

CicloMulsion® is ready-to-use lipid emulsions, i.e. do not need any step of preparation or dilution.

Production blinded labelling, packaging and delivering the study drugs in every participating centre of the trial will be performed by a company following European Union's Good Manufacturing Practice.

CicloMulsion® 5mg/ml is provided in colourless glass bottles sealed with a rubber stopper, containing a nominal fill volume of 50 ml.

The study treatment will be directly taken into the vial and injected via a catheter positioned within an antecubital vein. The injection will be performed slowly over 2 to 3 minutes.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eric Bonnefoy-Cudraz, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

CHU-Hôpital Cardiologique Louis Pradel BRON

Locations

CH Pays d'Aix

Aix-en-Provence, , France

Clinique de La Fourcade

Bayonne, , France

CHU Hopital Cardiologique Louis Pradel

Bron, , France

Hôpital Gabriel Montpied

Clermont-Ferrand, , France

Chu Hopital Du Bocage

Dijon, , France

Chu Hopital A Michallon

Grenoble, , France

Hopital St Luc St Joseph

Lyon, , France

Chu Arnaud de Villeneuve

Montpellier, , France

Hopital Guillaume Et Rene Laennec

Nantes, , France

Chu de Nimes

Nîmes, , France

Aphp Hopital Bichat

Paris, , France

Centre Hospitalier de Pau

Pau, , France

Chu de Bordeaux

Pessac, , France

Hopital Charles Nicolle

Rouen, , France

Nouvel Hôpital Civil

Strasbourg, , France

Chu de Rangueil

Toulouse, , France

Chru de Tours

Tours, , France

Chu de Nancy Brabois

Vandœuvre-lès-Nancy, , France

Countries

France

Other Identifiers

2012.754

Identifier Type: -

Identifier Source: org_study_id