Is Levosimendan Superior to Milrinone Regarding Acute Kidney Injury After Cardiac Surgery for Congenital Heart Disease?

Study Overview
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Brief Summary
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The aim of the study is to assess the ability of Levosimendan to reduce the postoperative acute kidney injury in pediatric patients undergoing surgery for congenital heart disease (CHDs). Young children, between the age of 1 to 12 months, with congenital heart disease in need of elective heart surgery will be included in this study. The trial will contain two study groups, 35 patients in each. One group will receive Levosimendan and the second group will receive Milrinone as a heart muscle-strengthening agent during and after the operation. Milrinone is currently used as the drug of choice in many pediatric cardiac surgery centers. It remains to see if Levosimendan can exert a kidney protecting function in addition to its heart muscle-strengthening properties. The primary objective of this study is to investigate the preventive effect of Levosimendan on postoperative acute kidney injury in pediatric patients undergoing surgery for their CHDs. Creatinine levels postoperatively will be the primary endpoint. Creatinine, the common marker of kidney injury, will be measured daily. The treatment with Levosimendan or Milrinone will be started during the operation (after initiation of cardiopulmonary bypass) and will last 24 hours. Blood samples will be obtained at six occasions perioperatively. Patients will be followed 4 days after termination of treatment (totally 5 days). The duration of study will be 30 days (24 hours treatment + 4 days follow up + 30-days-mortality registration). Creatinine is the primary outcome in this study. Inflammatory biomarkers and other relevant biomarkers will comprise the secondary outcome variables.

Official Title
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The Prophylactic Effect of Levosimendan in Reducting Acute Kidney Injury Postoperatively in Pediatric Patients Undergoing Corrective Heart Surgery

Conditions
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Congenital Heart Defects

Intervention / Treatment
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* Drug: Levosimendan
* Drug: Milrinone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent prior to any study specific procedures Female and male children between 1 and 12 months of age Non-restrictive VSD (corrective surgery) Complete AVSD (biventricular repair) Tetralogy of Fallot Exclusion Criteria: Unbalanced AtrioVentricular Septal Defect or AVSD with cyanosis Age less than one month and more than one year Acute operation that is unscheduled operation during the first 24 hours after presentation to the department for thoracic surgery Mild, moderate, or severe kidney dysfunction and known anatomical anomalies of kidneys Liver impairment or disease Ongoing infection Use of nephrotoxic drugs (like ibuprofen, angiotensin-converting-enzyme inhibitors, gentamicin, vancomycin) preoperative or postoperative until first post operative day. Contrast agents whithin 24 hours before operation. Use of inhibitors of membrane transport proteins (cimetidine, cetirizine, trimethoprim, probenecid, rifampin and gemfibrosil). Allergy to Levosimendan or substance included in the preparation or previous use of Levosimendan. Severe arrhythmias needing pace-maker treatment prior to the operation Severe cardiac dysfunction needing for treatment with extracorporeal membrane oxygenation (ECMO) prior to the operation. Preoperative need for mechanical ventilation and/or inotropic agents. Re-operation (open heart surgery). Earlier surgical closure of the arterial duct does not count as an exclusion criteria. Prematurity: Gestational age < 30 weeks, irrespective of postpartum age. Gestational age 30-34 weeks if patient is included at postpartum age under 3 months.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 12 Months

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Milrinone<br>In this arm the patients will receive Milrinone as an inotrope agent. Concentration: 0.2 mg/mL Infusion rate: 0.12 mL / kg / hr = Dose delivered 0.4 μg / kg / min --- Bolus dose: 1.44 ml / kg / hr in ten minutes (a maximum volume 0.24 ml / kg) = 48 μg / kg | Drug: Milrinone<br>* The drug infusion will be started after initiation of cardiopulmonary bypass and will continue for 24 hours.<br>|
| Experimental: Levosimendan<br>In this arm the patients will receive Levosimendan as an inotrope agent. Concentration: 0.05 mg/mL Infusion rate: 0.12 mL / kg / hr = Dose delivered 0.1 μg / kg / min --- Bolus dose: 1.44 ml / kg / hr in ten minutes (a maximum volume 0.24 ml / kg) = 12 μg/kg | Drug: Levosimendan<br>* The drug infusion will be started after initiation of cardiopulmonary bypass and will continue for 24 hours.<br>* Other names: Simdax;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum creatinine |  | Second postoperative day |