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

Phase 2

Completed

Brief Summary: 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).

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

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.

Arm && Interventions

Group	Intervention	Description
Milrinone	Milrinone	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
Levosimendan	Levosimendan	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

Primary Outcome Measures

Name	Time	Method
S-creatinine	One day after cardiac surgery	The primary outcome variable was the absolute value of serum creatinine data on postoperative day 1.

Secondary Outcome Measures

Name	Time	Method
30 Days Mortality	30 days	Mortality at 30th day
Acute Kidney Injury (AKI)	Two days (second postoperative day)	Secondary outcomes included the occurrence rate of AKI, defined as a 50% rise in serum creatinine, or more, within 48 hours after surgery. All stages of AKI (stage 1 and stage 2 and stage 3)

Locations (2): Children´s Hospital, Helsinki University Central Hospital
🇫🇮
Helsinki, Finland
Queen Silvia Children´s Hospital
🇸🇪
Göteborg, Västra Götaland, Sweden