CLOTILDE: Cyclosporine in Acute Myocardial Infarction Complicated by Cardiogenic Shock

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01901471

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Days)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myocardial Infarction	Drug: Single bolus of Placebo of CicloMulsion® (Neurovive). Drug: Single bolus of cyclosporine A (CicloMulsion®, Neurovive)	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Cyclosporine in Acute Myocardial Infarction Complicated by Cardiogenic Shock

Study Start Date :

Sep 1, 2015

Anticipated Primary Completion Date :

Oct 1, 2015

Anticipated Study Completion Date :

Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CsA Group	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.
Placebo Comparator: Placebo group	Drug: 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.

Arm

Intervention/Treatment

Experimental: CsA Group

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.

Placebo Comparator: Placebo group

Drug: 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.

Outcome Measures

Primary Outcome Measures

multiorgan failure evaluated by the SOFA score [At 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

multiorgan failure by SOFA score [At 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 scores [At 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 size [during 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 mortality [at 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 remodeling [at 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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CH Pays d'Aix	Aix-en-Provence	France	13616
2	Clinique de La Fourcade	Bayonne	France	64100
3	CHU Hopital Cardiologique Louis Pradel	Bron	France	69677
4	Hôpital Gabriel Montpied	Clermont-ferrand	France	63003
5	Chu Hopital Du Bocage	Dijon	France	21034
6	Chu Hopital A Michallon	Grenoble	France	38043
7	Hopital St Luc St Joseph	Lyon	France
8	Chu Arnaud de Villeneuve	Montpellier	France	34295
9	Hopital Guillaume Et Rene Laennec	Nantes	France	44093
10	Chu de Nimes	Nimes	France	30029
11	Aphp Hopital Bichat	Paris	France	75018
12	Centre Hospitalier de Pau	PAU	France	64011
13	Chu de Bordeaux	Pessac	France	33604
14	Hopital Charles Nicolle	Rouen	France	76031
15	Nouvel Hôpital Civil	Strasbourg	France	67091
16	Chu de Rangueil	Toulouse	France	31403
17	Chru de Tours	Tours	France	37044
18	Chu de Nancy Brabois	Vandoeuvre Les Nancy	France	54511