Is Levosimendan Superior to Milrinone Regarding Acute Kidney Injury After Cardiac Surgery for Congenital Heart Disease? (MiLe-1)

Göteborg University

Status and phase: Completed; Phase 2

Conditions: Congenital Heart Defects

Treatments: Drug: Milrinone; Drug: Levosimendan

Study type: Interventional

Funder types: Other

Identifiers

NCT02232399

2013-003105-25 (EudraCT Number)

MiLe-1

Details and patient eligibility

About

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).

Full 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.

Enrollment: 72 patients

Sex: All

Ages: 1 to 12 months old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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72 participants in 2 patient groups

Milrinone

Active Comparator group

Description:

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

Treatment:

Drug: Milrinone

Levosimendan

Experimental group

Description:

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

Treatment:

Drug: Levosimendan