title: Ciclosporin to Protect Renal function In Cardiac Surgery (CiPRICS): a study protocol for a double-blind, randomised, placebo-controlled, proof-of-concept study.
abstract: Acute kidney injury (AKI) after cardiac surgery is common and results in increased morbidity and mortality. One possible mechanism for AKI is ischaemia-reperfusion injury caused by the extracorporeal circulation (ECC), resulting in an opening of the mitochondrial permeability transition pore (mPTP) in the kidneys, which can lead to cell injury or cell death. Ciclosporin may block the opening of mPTP if administered before the ischaemia-reperfusion injury. We hypothesised that ciclosporin given before the start of ECC in cardiac surgery can decrease the degree of AKI.
  
  
  
  Ciclosporin to Protect Renal function In Cardiac Surgery (CiPRICS) study is an investigator-initiated double-blind, randomised, placebo-controlled, parallel design, single-centre study performed at a tertiary university hospital. The primary objective is to assess the safety and efficacy of ciclosporin to limit the degree of AKI in patients undergoing coronary artery bypass grafting surgery. We aim to evaluate 150 patients with a preoperative estimated glomerular filtration rate of 15-90 mL/min/1.73 m2. Study patients are randomised in a 1:1 ratio to receive study drug 2.5 mg/kg ciclosporin or placebo as an intravenous injection after anaesthesia induction but before start of surgery. The primary end point consists of relative P-cystatin C changes from the preoperative day to postoperative day 3. The primary variable will be tested using an analysis of covariance method. Secondary end points include evaluation of P-creatinine and biomarkers of kidney, heart and brain injury.
  
  
  
  The trial is conducted in compliance with the current version of the Declaration of Helsinki and the International Council for Harmonisation (ICH) Good Clinical Practice guidelines E6 (R1) and was approved by the Regional Ethical Review Board, Lund and the Swedish Medical Products Agency (MPA). Written and oral informed consent is obtained before enrolment into the study.
  
  
  
  NCT02397213; Pre-results.
authors.affiliation: Department of Anesthesiology and Intensive Care, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
authors.forename: Per
authors.identifier: 0000-0003-1951-7723
authors.initials: P
authors.lastname: Ederoth
authors.affiliation: Department of Anesthesiology and Intensive Care, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
authors.forename: Edgars
authors.initials: E
authors.lastname: Grins
authors.affiliation: Department of Anesthesiology and Intensive Care, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
authors.forename: Alain
authors.initials: A
authors.lastname: Dardashti
authors.affiliation: Department of Anesthesiology and Intensive Care, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Brondén
authors.affiliation: Department of Anesthesiology and Intensive Care, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
authors.forename: Carsten
authors.initials: C
authors.lastname: Metzsch
authors.affiliation: Department of Anesthesiology and Intensive Care, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
authors.forename: André
authors.initials: A
authors.lastname: Erdling
authors.affiliation: Department of Cardiothoracic Surgery, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
authors.forename: Shahab
authors.initials: S
authors.lastname: Nozohoor
authors.affiliation: Department of Cardiothoracic Surgery, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
authors.forename: Arash
authors.initials: A
authors.lastname: Mokhtari
authors.affiliation: Department of Mitochondrial Medicine, Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Magnus J
authors.initials: MJ
authors.lastname: Hansson
authors.affiliation: Department of Mitochondrial Medicine, Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Eskil
authors.initials: E
authors.lastname: Elmér
authors.affiliation: Department of Anesthesiology and Intensive Care, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Algotsson
authors.affiliation: Fredrik Meijer Heart and Vascular Institute Spectrum Health, MI US Van Andel Institute, Grand Rapids, Michigan, USA.|Cardiovascular Institute, Stanford University, Stanford, California, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Jovinge
authors.affiliation: Department of Cardiothoracic Surgery, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Bjursten
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology; D015415:Biomarkers; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage*; D004311:Double-Blind Method; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006785:Hospitals, University; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects; D000083162:Mitochondrial Permeability Transition Pore; D011183:Postoperative Complications / Q000188:drug therapy* / Q000517:prevention & control; D011300:Preoperative Care / Q000379:methods*; D000075082:Proof of Concept Study; D015427:Reperfusion Injury / Q000517:prevention & control; D012107:Research Design; D013548:Sweden
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D016572:Cyclosporine; D003404:Creatinine