Clinical trial NCT02232399: Is Levosimendan Superior to Milrinone Regarding Acute Kidney Injury After Cardiac Surgery for Congenital Heart Disease?
Official title: The Prophylactic Effect of Levosimendan in Reducting Acute Kidney Injury Postoperatively in Pediatric Patients Undergoing Corrective Heart Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Congenital Heart Defects
Lead sponsor: Göteborg University
Sponsor class: OTHER
Collaborators: name: Helsinki University Central Hospital
First posted: 2014-09-05
Enrollment: 72
Sex: ALL
Minimum age (years): 1
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures
2. Female and male children between 1 and 12 months of age
3. Non-restrictive VSD (corrective surgery)
4. Complete AVSD (biventricular repair)
5. Tetralogy of Fallot

Exclusion Criteria:

1. Unbalanced AtrioVentricular Septal Defect or AVSD with cyanosis
2. Age less than one month and more than one year
3. Acute operation that is unscheduled operation during the first 24 hours after presentation to the department for thoracic surgery
4. Mild, moderate, or severe kidney dysfunction and known anatomical anomalies of kidneys
5. Liver impairment or disease
6. Ongoing infection
7. 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.
8. Use of inhibitors of membrane transport proteins (cimetidine, cetirizine, trimethoprim, probenecid, rifampin and gemfibrosil).
9. Allergy to Levosimendan or substance included in the preparation or previous use of Levosimendan.
10. Severe arrhythmias needing pace-maker treatment prior to the operation
11. Severe cardiac dysfunction needing for treatment with extracorporeal membrane oxygenation (ECMO) prior to the operation.
12. Preoperative need for mechanical ventilation and/or inotropic agents.
13. Re-operation (open heart surgery). Earlier surgical closure of the arterial duct does not count as an exclusion criteria.
14. Prematurity: Gestational age \< 30 weeks, irrespective of postpartum age. Gestational age 30-34 weeks if patient is included at postpartum age under 3 months.

Primary outcomes:
measure: S-creatinine
timeFrame: One day after cardiac surgery
Secondary outcomes:
measure: Acute Kidney Injury (AKI)
timeFrame: Two days (second postoperative day)
measure: 30 Days Mortality
timeFrame: 30 days
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Children´s Hospital, Helsinki University Central Hospital
city: Göteborg
country: Sweden
facility: Queen Silvia Children´s Hospital
state: Västra Götaland
Study officials:
affiliation: Queen Silvia Children´s Hospital, Department of anesthesia and intensive care
name: Albert Castellheim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Queen Silvia Children´s Hospital, Department of pediatric cardiology
name: Håkan Wåhlander, MD, PhD
role: STUDY_CHAIR
affiliation: Queen Silvia Children´s Hospital, Department of anesthesiology and intensive care
name: Birgitta Romlin, MD, PhD
role: STUDY_CHAIR
affiliation: Queen Silvia Children´s Hospital, Department of anesthesiology and intensive care
name: Elin Thorlacius, MD
role: STUDY_CHAIR
affiliation: Sahlgrenska University Hospital, Department of anesthesiology and intensive care
name: Sven-Erik Ricksten, MD, PhD
role: STUDY_CHAIR
References:
citation: Thorlacius EM, Vistnes M, Ojala T, Keski-Nisula J, Molin M, Romlin BS, Synnergren M, Ricksten SE, Wahlander H, Castellheim A. Levosimendan Versus Milrinone and Release of Myocardial Biomarkers After Pediatric Cardiac Surgery: Post Hoc Analysis of Clinical Trial Data. Pediatr Crit Care Med. 2021 Jul 1;22(7):e402-e409. doi: 10.1097/PCC.0000000000002712.