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

Congenital Heart Defects Clinical Trial

— MiLe-1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02232399
• Other study ID #: MiLe-1
• Secondary ID: 2013-003105-25
• Status: Completed
• Phase: Phase 2
• Start date: October 15, 2014
• Est. completion date: April 25, 2017

Study information

• Verified date: March 2024
• Source: Göteborg University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: April 25, 2017
• Est. primary completion date: April 25, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 12 Months

Eligibility

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.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Congenital Heart Defects
• Heart Defects, Congenital

Intervention

Drug:
• Levosimendan
The drug infusion will be started after initiation of cardiopulmonary bypass and will continue for 24 hours.
• Milrinone
The drug infusion will be started after initiation of cardiopulmonary bypass and will continue for 24 hours.

Locations

Country	Name	City	State
Finland	Children´s Hospital, Helsinki University Central Hospital	Helsinki
Sweden	Queen Silvia Children´s Hospital	Göteborg	Västra Götaland

Sponsors (2)

Lead Sponsor	Collaborator
Göteborg University	Helsinki University Central Hospital

Countries where clinical trial is conducted

Finland,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	S-creatinine	The primary outcome variable was the absolute value of serum creatinine data on postoperative day 1.	One day after cardiac surgery
Secondary	Acute Kidney Injury (AKI)	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)	Two days (second postoperative day)
Secondary	30 Days Mortality	Mortality at 30th day	30 days