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

NCT02232399 | Completed Phase 2 Results DMC

• 2 other identifiers: MiLe-12013-003105-25
• Study Type: interventional
• Target: 72
• Locations: 2 countries
• Sites: 2

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).

Conditions

Congenital Heart Defects

Outcome Measures

Primary Outcomes (1)

• S-creatinine

  The primary outcome variable was the absolute value of serum creatinine data on postoperative day 1.

  One day after cardiac surgery

Secondary Outcomes (2)

• Acute Kidney Injury (AKI)

  Two days (second postoperative day)

• 30 Days Mortality

  30 days

Study Arms (2)

Milrinone

ACTIVE COMPARATOR

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

Drug: Milrinone

Levosimendan

EXPERIMENTAL

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

Drug: Levosimendan

Interventions

Levosimendan DRUG

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

Also known as: Simdax

Levosimendan

Milrinone DRUG

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

Also known as: Corotrop

Milrinone

Eligibility Criteria

• Age: 1 Month - 12 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.
• Prematurity: Gestational age \< 30 weeks, irrespective of postpartum age. Gestational age 30-34 weeks if patient is included at postpartum age under 3 months.

Sponsors & Collaborators

• Göteborg University: lead
• Helsinki University Central Hospital: collaborator

Study Sites (2)

Children´s Hospital, Helsinki University Central Hospital

Helsinki, FIN-00029 HYKS, Finland

Location

Queen Silvia Children´s Hospital

Gothenburg, Västra Götaland County, 416 85, Sweden

Location

Related Publications (1)

• 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.

  PMID: 33739957 DERIVED

MeSH Terms

Conditions

Heart Defects, Congenital

Interventions

Simendan; Milrinone

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Hydrazones; Hydrazines; Organic Chemicals; Pyridazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Amrinone; Aminopyridines; Amines; Pyridines

Limitations and Caveats

1. The trial included merely three types of heart defects with relatively short CPB-times. Patient with higher risk for postoperative AKI were excluded (patients with univentricular circulation, renal disease, history of open-heart surgery or receiving nephrotoxic agents 2. Unequal number of patients in the study groups (due to use of the stratification program which was set to stratify the patients according to age and diagnosis).

Results Point of Contact

• Title: Prof. Albert Gyllencreutz Castellheim
• Organization: University of Gothenburg

albert.castellheim@gu.se

+46708979820

Study Officials

• Albert Castellheim, MD, PhD

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

  PRINCIPAL INVESTIGATOR

• Håkan Wåhlander, MD, PhD

  Queen Silvia Children´s Hospital, Department of pediatric cardiology

  STUDY CHAIR

• Birgitta Romlin, MD, PhD

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

  STUDY CHAIR

• Elin Thorlacius, MD

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

  STUDY CHAIR

• Sven-Erik Ricksten, MD, PhD

  Sahlgrenska University Hospital, Department of anesthesiology and intensive care

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: September 2, 2014
• First Posted: September 5, 2014
• Study Start: October 15, 2014
• Primary Completion: April 25, 2017
• Study Completion: April 25, 2017
• Last Updated: March 26, 2024
• Results First Posted: March 26, 2024

Record last verified: 2024-03

Locations

FI (1); SE (1)