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

NCT01002859 | Terminated Phase 2 DMC

• 1 other identifier: DCIC 08 04
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Coronary Artery Bypass Surgery; Cardiopulmonary Bypass

Keywords

Coronary artery bypass graft surgery (CABG); Cardiopulmonary Bypass (CPB); Cyclosporine; ischaemia reperfusion

Outcome Measures

Primary Outcomes (1)

• Area under curve and maximal blood level of both troponin-T and Creatine Kinase-MB after cardiopulmonary bypass

  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.

Secondary Outcomes (4)

• Area under curve and maximal blood level of S100β protein

  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

• 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)....)

  until Day 3 after the end of the cardiopulmonary bypass

• Levels of inflammatory cytokines (TNF alpha , IL-1 alpha et IL-1 beta, IL-6, IL-8, IL-10). C-reactive protein (CRP) level

  until day 8 after the end of the cardiopulmonary bypass

• Creatine blood levels

  until 3 months after the end of the cardiopulmonary bypass

Study Arms (2)

cyclosporin

ACTIVE COMPARATOR

Intravenous cyclosporin injection.

Drug: Sandimmum

Pacebo

PLACEBO COMPARATOR

Intravenous injection of NaCl solution.

Drug: Placebo

Interventions

Sandimmum DRUG

Intravenous injection of cyclosporine

cyclosporin

Placebo DRUG

Intravenous Injection of NaCl solution

Pacebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Study Sites (1)

Department of cardiac surgery - University Hospital of Grenoble

Grenoble, 38043, France

Location

Related Publications (5)

• Crompton M. The mitochondrial permeability transition pore and its role in cell death. Biochem J. 1999 Jul 15;341 ( Pt 2)(Pt 2):233-49.

  PMID: 10393078 BACKGROUND

• Halestrap AP, Clarke SJ, Javadov SA. Mitochondrial permeability transition pore opening during myocardial reperfusion--a target for cardioprotection. Cardiovasc Res. 2004 Feb 15;61(3):372-85. doi: 10.1016/S0008-6363(03)00533-9.

  PMID: 14962470 BACKGROUND

• Hausenloy DJ, Duchen MR, Yellon DM. Inhibiting mitochondrial permeability transition pore opening at reperfusion protects against ischaemia-reperfusion injury. Cardiovasc Res. 2003 Dec 1;60(3):617-25. doi: 10.1016/j.cardiores.2003.09.025.

  PMID: 14659807 BACKGROUND

• Shanmuganathan S, Hausenloy DJ, Duchen MR, Yellon DM. Mitochondrial permeability transition pore as a target for cardioprotection in the human heart. Am J Physiol Heart Circ Physiol. 2005 Jul;289(1):H237-42. doi: 10.1152/ajpheart.01192.2004.

  PMID: 15961375 BACKGROUND

• Piot C, Croisille P, Staat P, Thibault H, Rioufol G, Mewton N, Elbelghiti R, Cung TT, Bonnefoy E, Angoulvant D, Macia C, Raczka F, Sportouch C, Gahide G, Finet G, Andre-Fouet X, Revel D, Kirkorian G, Monassier JP, Derumeaux G, Ovize M. Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N Engl J Med. 2008 Jul 31;359(5):473-81. doi: 10.1056/NEJMoa071142.

  PMID: 18669426 BACKGROUND

Study Officials

• Vincent BACH, MD

  Cardiac Surgery Department - University Hospital of Grenoble,

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2009
• First Posted: October 27, 2009
• Study Start: April 1, 2009
• Primary Completion: May 1, 2011
• Study Completion: July 1, 2011
• Last Updated: September 5, 2014

Record last verified: 2014-09

Locations

FR (1)