Ciclosporin to Protect Renal Function In Cardiac Surgery

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the potential of ciclosporin in reducing risk and degree of acute kidney injury after cardiac surgery.

Detailed Description
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Acute kidney injury (AKI) is a common complication after cardiac surgery and is associated with decreased long-term survival. The mechanism for inducing acute kidney injury is unknown but ischaemia-reperfusion injury is indicated to be a part of the cause. Animal studies have showed cytoprotective, preconditioning and anti-apoptotic effects of ciclosporin in ischaemia-reperfusion injury in the kidney. The major mechanism is thought to be inhibition of the reperfusion triggered opening of the mitochondrial permeability transition pore (mPTP), responsible for reperfusion-induced necrosis. During cardiac surgery, the period of extracorporeal circulation (ECC) changes the perfusion through the kidney. Return to normal perfusion with a beating heart has similarities with reperfusion following ischemia. Administration of ciclosporin in conjunction with percutaneous coronary intervention (PCI), heart surgery and traumatic brain injury (TBI) in humans has shown to be safe with no direct side-effects. The investigators therefore hypothesize that a preconditioning effect of ciclosporin before coronary artery bypass grafting (CABG) can reduce the level of renal dysfunction after this type of cardiac surgery.

Official Title
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Ciclosporin to Protect Renal Function In Cardiac Surgery: CiPRICS A Phase II Double Blind Randomized Placebo Controlled Study

Conditions
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Acute Kidney Injury

Intervention / Treatment
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* Drug: Ciclosporin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-emergent CABG Written informed consent to participate Preoperative CyC eGFR or MDRD eGFR is 90-15. Exclusion Criteria: Uncontrolled hypertension Hypersensitivity to ciclosporin or any of the excipients of the lipid emulsion, including egg-, soya- or peanut protein Pregnancy or fertile woman Ciclosporin treatment within 4 weeks Ongoing malignancy, ongoing immunosuppressive treatment, severe hepatic dysfunction, dialysis or severe infection Ongoing medication with dabigatran, aliskiren, bosentan, stiripentol, glibenclamid, St John's worth, or Off-pump surgery
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>All components of the CicloMulsion® emulsion except ciclosporin: soybean oil (refined), triglycerides (medium-chain), egg lecithin, glycerol, oleic acid, sodium hydroxide and water for injection (=0.5 ml/kg). | Drug: Placebo<br>* All components of the CicloMulsion® emulsion except ciclosporin: soybean oil (refined), triglycerides (medium-chain), egg lecithin, glycerol, oleic acid, sodium hydroxide and water for injection (=0.5 ml/kg).<br>|
| Active Comparator: Ciclosporin<br>Single dose of CicloMulsion® 5 mg/ml, 2.5 mg/kg (=0.5 ml/kg) as intravenous injection. | Drug: Ciclosporin<br>* Single dose of CicloMulsion® 5 mg/ml, 2.5 mg/kg (=0.5 ml/kg) as intravenous injection preoperatively after anesthesia induction.<br>* Other names: CicloMulsion® ATC-code: CO1EB;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ciclosporin to Protect Renal function In Cardiac Surgery. | Relative P-CyC change from day -1 to day 3. | up to day 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac surgery, Ciclosporin, Acute Kidney injury, Ischemia, Safety, Cystatin C