Effect of Preliminary Administration of Cyclosporine (Sandimmun ®) on Different Markers of Cardiac Ischaemia Induced by Cardiopulmonary Bypass (Ciclo et CEC)

This study has been terminated.
(difficulties to include patients)
Sponsor:
Information provided by (Responsible Party):
University Hospital, Grenoble
ClinicalTrials.gov Identifier:
NCT01002859
First received: October 26, 2009
Last updated: September 4, 2014
Last verified: September 2014
  Purpose

Observe the effect of preliminary cyclosporine administration on different markers of cardiac ischaemia led by the aortic cross-clamp during coronary artery bypass surgery with Cardiopulmonary bypass.


Condition Intervention Phase
Coronary Artery Bypass Surgery
Cardiopulmonary Bypass
Drug: Sandimmum
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Double-Blind Phase II Pilot Monocentric Randomized Clinical Trial Evaluating the Effect of a Preliminary Administration of Cyclosporine on Different Markers of Cardiac Ischemia Led by the Aortic Cross-clamp During Coronary Artery Bypass Surgery With Cardiopulmonary Bypass.

Resource links provided by NLM:


Further study details as provided by University Hospital, Grenoble:

Primary Outcome Measures:
  • Area under curve and maximal blood level of both troponin-T and Creatine Kinase-MB after cardiopulmonary bypass [ Time Frame: at anaesthesia (ti), at the end of the cardiopulmonary bypass (t0), and 6 h, 12 h, 24 h,48h and 72h after the end of the cardiopulmonary bypass. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Area under curve and maximal blood level of S100β protein [ Time Frame: at anaesthesia (ti), at the end of the cardiopulmonary bypass (t0), and 6 h, 12 h, 24 h,48h and 72h after the end of the cardiopulmonary bypass ] [ Designated as safety issue: Yes ]
  • Spontaneous defibrillation at aorta declamping; Post surgical atrial fibrillation; ECG (new Q wave); Transthoracic Echocardiogram (diastolic and systolic function study, research of paradoxical septal motion, study of cardiac output)....) [ Time Frame: until Day 3 after the end of the cardiopulmonary bypass ] [ Designated as safety issue: Yes ]
  • Levels of inflammatory cytokines (TNF alpha , IL-1 alpha et IL-1 beta, IL-6, IL-8, IL-10). C-reactive protein (CRP) level [ Time Frame: until day 8 after the end of the cardiopulmonary bypass ] [ Designated as safety issue: Yes ]
  • Creatine blood levels [ Time Frame: until 3 months after the end of the cardiopulmonary bypass ] [ Designated as safety issue: Yes ]

Enrollment: 50
Study Start Date: April 2009
Study Completion Date: July 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: cyclosporin
Intravenous cyclosporin injection.
Drug: Sandimmum
Intravenous injection of cyclosporine
Placebo Comparator: Pacebo
Intravenous injection of NaCl solution.
Drug: Placebo
Intravenous Injection of NaCl solution

Detailed Description:

The coronary artery bypass surgery, in spite of substantial improvements during the last years, is still associated to a post-operative mortality and morbidity: myocardial infarction, heart failure, cardiac arrhythmia, renal failure, Stroke.

These complications are often due to ischaemia - reperfusion injury event. Recent studies showed that in case of cellular stress (in particular during the reperfusion after ischaemia) a not specific pore, called Mitochondrial permeability transition Pore (MPTP), could be opened. That caused the loss of ion homeostasis, then cell death as well as by apoptosis as by necrosis.

Prevent the opening of this MPTP during the myocardial reperfusion after coronary bypass, for example, is an important objective to improve the cardioprotection.

The Cyclosporin A, prevents the MPTP from opening. Several studies have shown an cytoprotection led by cyclosporin A, after ischaemia reperfusion in several models as isolated rats heart, in vivo rats heart and ex vivo myocardial ( atrial ) human tissues.

Recently, a multicentric study performed in humans, during the acute phase of myocardial infarction, showed a reduction of infarct size by approximately 40% in the cyclosporine group compared to control group.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient hospitalized for a coronary artery bypass surgery
  • Not urgent surgery
  • Left ventricular ejection fraction (LVEF)> 40 %
  • 18 years and older
  • patient who have sign the informed consent form
  • Affiliation to the French Social Security.

Exclusion Criteria:

  • Beating heart surgery with or without Cardiopulmonary Bypass
  • Patient receiving another surgical gesture combined to the CABG
  • Myocardial infarction or vascular cerebral attack less than 30 days
  • Previous History of cardiac surgery;
  • Renal failure (creatinine > 200 µmol/l)
  • Uncontrolled hypertension
  • hyperkaliemy;
  • hyperuricemy;
  • Acute Coronary Syndrome
  • Malignant tumor
  • Unchecked infection
  • Previous intravenous administration of Sandimmun ®;
  • allergy to ciclosporin, ethyl alcohol, castor oil or nitrogen
  • Pregnant Woman, parturient without contraception, or breast-feeding
  • Age < 18 years
  • Patient who have not signed the form of consent;
  • Patient Under guardianship or being the object of a legal protective measure
  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: NCT01002859

Locations
France
Department of cardiac surgery - University Hospital of Grenoble
Grenoble,, France, 38043
Sponsors and Collaborators
University Hospital, Grenoble
Investigators
Principal Investigator: Vincent BACH, MD Cardiac Surgery Department - University Hospital of Grenoble,
  More Information

Publications:
Responsible Party: University Hospital, Grenoble
ClinicalTrials.gov Identifier: NCT01002859     History of Changes
Other Study ID Numbers: DCIC 08 04
Study First Received: October 26, 2009
Last Updated: September 4, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Grenoble:
Coronary artery bypass graft surgery (CABG)
Cardiopulmonary Bypass (CPB)
Cyclosporine
ischaemia reperfusion

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Pathologic Processes
Cyclosporins
Cyclosporine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 11, 2014