Cyclosporine in Acute Myocardial Infarction Complicated by Cardiogenic Shock (CLOTILDE)

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon
ClinicalTrials.gov Identifier:
NCT01901471
First received: July 11, 2013
Last updated: March 15, 2016
Last verified: March 2016
  Purpose
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 Intervention Phase
Acute Myocardial Infarction
Drug: Single bolus of Placebo of CicloMulsion® (Neurovive).
Drug: Single bolus of cyclosporine A (CicloMulsion®, Neurovive)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Cyclosporine in Acute Myocardial Infarction Complicated by Cardiogenic Shock

Resource links provided by NLM:


Further study details as provided by Hospices Civils de Lyon:

Primary Outcome Measures:
  • multiorgan failure evaluated by the SOFA score [ Time Frame: At 24 hours after admission ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: At 48 hours after admission ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: At 24 hours and at 48 hours ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: At 24 hours after inclusion ] [ Designated as safety issue: No ]
    The hemodynamic changes will be estimated by measuring the cardiac output (CO) obtained by echocardiography.

  • Reduction of infarct size [ Time Frame: during the first 72 hours after admission ] [ Designated as safety issue: No ]
    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 [ Time Frame: at 1 month ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: at 1 month ] [ Designated as safety issue: Yes ]
    Left ventricular remodeling will be assessed at 1 month among surviving patients by measurement of left ventricular end-diastolic volume by transthoracic echocardiography


Enrollment: 0
Study Start Date: September 2015
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01901471

Locations
France
CH Pays d'Aix
Aix-en-Provence, France, 13616
Clinique de La Fourcade
Bayonne, France, 64100
CHU Hopital Cardiologique Louis Pradel
Bron, France, 69677
Hôpital Gabriel Montpied
Clermont-ferrand, France, 63003
Chu Hopital Du Bocage
Dijon, France, 21034
Chu Hopital A Michallon
Grenoble, France, 38043
Hopital St Luc St Joseph
Lyon, France
Chu Arnaud de Villeneuve
Montpellier, France, 34295
Hopital Guillaume Et Rene Laennec
Nantes, France, 44093
Chu de Nimes
Nimes, France, 30029
Aphp Hopital Bichat
Paris, France, 75018
Centre Hospitalier de Pau
PAU, France, 64011
Chu de Bordeaux
Pessac, France, 33604
Hopital Charles Nicolle
Rouen, France, 76031
Nouvel Hôpital Civil
Strasbourg, France, 67091
Chu de Rangueil
Toulouse, France, 31403
Chru de Tours
Tours, France, 37044
Chu de Nancy Brabois
Vandoeuvre Les Nancy, France, 54511
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
Principal Investigator: Eric Bonnefoy-Cudraz, MD, PhD CHU-Hôpital Cardiologique Louis Pradel BRON
  More Information

Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT01901471     History of Changes
Other Study ID Numbers: 2012.754 
Study First Received: July 11, 2013
Last Updated: March 15, 2016
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Hospices Civils de Lyon:
Cyclosporine, cardiogenic shock, SOFA score,

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

ClinicalTrials.gov processed this record on July 21, 2016