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

NCT ID: NCT02232399

Last Updated: 2024-03-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-15
• Study Completion Date: 2017-04-25

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.

Conditions

Congenital Heart Defects

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Milrinone

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Levosimendan

Intervention Type: DRUG

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

Interventions

Levosimendan

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

Intervention Type: DRUG

Milrinone

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

Intervention Type: DRUG

Other Intervention Names

Simdax; Corotrop

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.

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.

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 12 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Helsinki University Central Hospital

OTHER

Sponsor Role: collaborator

Göteborg University

OTHER

Sponsor Role: lead

Responsible Party

Albert Castellheim

Associate professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Albert Castellheim, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Queen Silvia Children´s Hospital, Department of anesthesia and intensive care

Håkan Wåhlander, MD, PhD

Role: STUDY_CHAIR

Queen Silvia Children´s Hospital, Department of pediatric cardiology

Birgitta Romlin, MD, PhD

Role: STUDY_CHAIR

Queen Silvia Children´s Hospital, Department of anesthesiology and intensive care

Elin Thorlacius, MD

Role: STUDY_CHAIR

Queen Silvia Children´s Hospital, Department of anesthesiology and intensive care

Sven-Erik Ricksten, MD, PhD

Role: STUDY_CHAIR

Sahlgrenska University Hospital, Department of anesthesiology and intensive care

Locations

Children´s Hospital, Helsinki University Central Hospital

Helsinki, , Finland

Queen Silvia Children´s Hospital

Gothenburg, Västra Götaland County, Sweden

Countries

Finland; Sweden

References

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.

Reference Type: DERIVED

PMID: 33739957 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2013-003105-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MiLe-1

Identifier Type: -

Identifier Source: org_study_id