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

Primary Purpose

Congenital Heart Defects

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Levosimendan

Milrinone

About this trial

This is an interventional prevention trial for Congenital Heart Defects

Eligibility Criteria

1 Month - 12 Months (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Children´s Hospital, Helsinki University Central Hospital
Queen Silvia Children´s Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Milrinone

Levosimendan

Arm 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

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

Outcomes

Primary Outcome Measures

Serum creatinine

Secondary Outcome Measures

Full Information

NCT ID

NCT02232399

First Posted

September 2, 2014

Last Updated

April 25, 2017

Sponsor

Göteborg University

Collaborators

Helsinki University Central Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02232399

Brief Title

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

Acronym

MiLe-1

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2017

Overall Recruitment Status

Completed

Study Start Date

October 2014 (undefined)

Primary Completion Date

April 25, 2017 (Actual)

Study Completion Date

April 25, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Göteborg University

Collaborators

Helsinki University Central Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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). 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Congenital Heart Defects

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare Provider

Allocation

Randomized

Enrollment

72 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Milrinone

Arm Type

Active Comparator

Arm Description

Arm Title

Levosimendan

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Levosimendan

Other Intervention Name(s)

Simdax

Intervention Description

The drug infusion will be started after initiation of cardiopulmonary bypass and will continue for 24 hours.

Intervention Type

Drug

Intervention Name(s)

Milrinone

Intervention Description

The drug infusion will be started after initiation of cardiopulmonary bypass and will continue for 24 hours.

Primary Outcome Measure Information:

Title

Serum creatinine

Time Frame

Second postoperative day

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Month

Maximum Age & Unit of Time

12 Months

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials: