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

Primary Purpose

Acute Myocardial Infarction

Status
Withdrawn
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Single bolus of Placebo of CicloMulsion® (Neurovive).
Single bolus of cyclosporine A (CicloMulsion®, Neurovive)
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myocardial Infarction focused on measuring Cyclosporine, cardiogenic shock, SOFA score,

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • CH Pays d'Aix
  • Clinique de La Fourcade
  • CHU Hopital Cardiologique Louis Pradel
  • Hôpital Gabriel Montpied
  • Chu Hopital Du Bocage
  • Chu Hopital A Michallon
  • Hopital St Luc St Joseph
  • Chu Arnaud de Villeneuve
  • Hopital Guillaume Et Rene Laennec
  • Chu de Nimes
  • Aphp Hopital Bichat
  • Centre Hospitalier de Pau
  • Chu de Bordeaux
  • Hopital Charles Nicolle
  • Nouvel Hôpital Civil
  • Chu de Rangueil
  • Chru de Tours
  • Chu de Nancy Brabois

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

CsA Group

Placebo group

Arm Description

Outcomes

Primary Outcome Measures

multiorgan failure evaluated by the SOFA score
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
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
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)
The hemodynamic changes will be estimated by measuring the cardiac output (CO) obtained by echocardiography.
Reduction of infarct size
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
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
Left ventricular remodeling will be assessed at 1 month among surviving patients by measurement of left ventricular end-diastolic volume by transthoracic echocardiography

Full Information

First Posted
July 11, 2013
Last Updated
March 15, 2016
Sponsor
Hospices Civils de Lyon
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1. Study Identification

Unique Protocol Identification Number
NCT01901471
Brief Title
Cyclosporine in Acute Myocardial Infarction Complicated by Cardiogenic Shock
Acronym
CLOTILDE
Official Title
Cyclosporine in Acute Myocardial Infarction Complicated by Cardiogenic Shock
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Withdrawn
Study Start Date
September 2015 (undefined)
Primary Completion Date
October 2015 (Anticipated)
Study Completion Date
October 2015 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon

4. Oversight

Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myocardial Infarction
Keywords
Cyclosporine, cardiogenic shock, SOFA score,

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CsA Group
Arm Type
Experimental
Arm Title
Placebo group
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Single bolus of Placebo of CicloMulsion® (Neurovive).
Intervention Description
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
Intervention Name(s)
Single bolus of cyclosporine A (CicloMulsion®, Neurovive)
Intervention Description
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.
Primary Outcome Measure Information:
Title
multiorgan failure evaluated by the SOFA score
Description
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.
Time Frame
At 24 hours after admission
Secondary Outcome Measure Information:
Title
multiorgan failure by SOFA score
Description
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.
Time Frame
At 48 hours after admission
Title
multiorgan failure by SAPSII scores
Description
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.
Time Frame
At 24 hours and at 48 hours
Title
Cardiac output (CO)
Description
The hemodynamic changes will be estimated by measuring the cardiac output (CO) obtained by echocardiography.
Time Frame
At 24 hours after inclusion
Title
Reduction of infarct size
Description
evaluation of the under curve area of serum creatinin kinase (CK) measured during the 72 first hours after admission (12 blood sampling).
Time Frame
during the first 72 hours after admission
Title
Reduction of cardiovascular morbidity and mortality
Description
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.
Time Frame
at 1 month
Title
Reduction of Left ventricular remodeling
Description
Left ventricular remodeling will be assessed at 1 month among surviving patients by measurement of left ventricular end-diastolic volume by transthoracic echocardiography
Time Frame
at 1 month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric Bonnefoy-Cudraz, MD, PhD
Organizational Affiliation
CHU-Hôpital Cardiologique Louis Pradel BRON
Official's Role
Principal Investigator
Facility Information:
Facility Name
CH Pays d'Aix
City
Aix-en-Provence
ZIP/Postal Code
13616
Country
France
Facility Name
Clinique de La Fourcade
City
Bayonne
ZIP/Postal Code
64100
Country
France
Facility Name
CHU Hopital Cardiologique Louis Pradel
City
Bron
ZIP/Postal Code
69677
Country
France
Facility Name
Hôpital Gabriel Montpied
City
Clermont-ferrand
ZIP/Postal Code
63003
Country
France
Facility Name
Chu Hopital Du Bocage
City
Dijon
ZIP/Postal Code
21034
Country
France
Facility Name
Chu Hopital A Michallon
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Hopital St Luc St Joseph
City
Lyon
Country
France
Facility Name
Chu Arnaud de Villeneuve
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
Hopital Guillaume Et Rene Laennec
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Chu de Nimes
City
Nimes
ZIP/Postal Code
30029
Country
France
Facility Name
Aphp Hopital Bichat
City
Paris
ZIP/Postal Code
75018
Country
France
Facility Name
Centre Hospitalier de Pau
City
PAU
ZIP/Postal Code
64011
Country
France
Facility Name
Chu de Bordeaux
City
Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
Hopital Charles Nicolle
City
Rouen
ZIP/Postal Code
76031
Country
France
Facility Name
Nouvel Hôpital Civil
City
Strasbourg
ZIP/Postal Code
67091
Country
France
Facility Name
Chu de Rangueil
City
Toulouse
ZIP/Postal Code
31403
Country
France
Facility Name
Chru de Tours
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
Chu de Nancy Brabois
City
Vandoeuvre Les Nancy
ZIP/Postal Code
54511
Country
France

12. IPD Sharing Statement

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Cyclosporine in Acute Myocardial Infarction Complicated by Cardiogenic Shock

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