Levosimendan Pharmacokinetics in Children (LevoCorKids)

Pharmacokinetics of Levosimendan in Children With Acute Heart Failure

Levosimendan is a drug used in patients with heart failure and has several advantages over other heart failure drugs. A lot of research has been done with Levosimendan in Adults, and the way the body handles the drug (pharmacokinetics) and responds to the drug (pharmacodynamics) are well established. But, in children this information is lacking despite the fact that Levosimendan is increasingly used in children of all ages. The investigators aim to describe which Levosimendan dose leads to which drug levels in children of different ages.

Study Overview

• Status: Unknown
• Conditions: Acute Heart Failure

Detailed Description

Rationale: Levosimendan, a calcium-sensitizer, is a relatively new inotropic drug with the benefit over conventional inotropes that it does not increase myocardial oxygen demand or lead to arrhythmias. Levosimendan has a relatively unique pharmacokinetic profile, after a 24 hour infusion its clinical effects remain for several days. This is achieved through the continuing haemodynamic effects of its active metabolites, which have a half life of approximately 80 hours compared to 1 hour of Levosimendan itself. Levosimendan has been extensively studied in adults and is used in ischemic heart disease, acute heart failure, chronic heart failure, following cardiac surgery, and in septic shock. Due to the inotropic properties and its strong pulmonary vasodilatory effect, Levosimendan could also be very useful as perioperative therapy in children with congenital heart disease, low cardiac output, or pulmonary artery hypertension.

Although experience with levosimendan in children is still scarce in the literature, initial reports have been promising and Levosimendan is used more and more often as a (rescue) therapy in children with heart failure. However, current dosing regimens in children are based on adult pharmacokinetic evidence. One pediatric report suggests that the pharmacokinetic profile of a single loading dose of Levosimendan is probably similar in children older than 6 months compared to adults. The pharmacokinetic profile of a 24-hour infusion of Levosimendan has not yet been studied in children. It is very important to study the pharmacokinetics of this useful drug in different age groups because of the diversity of the population due to age, volume of distribution, ontogeny of the metabolizing enzymes, and the influence of disease state on pharmacokinetics and pharmacodynamics.

Objective: To describe the pharmacokinetic profile of a 24 hour infusion of levosimendan and its active metabolites in children with acute or chronic heart failure.

Study design: Observational study of Levosimendan levels in children treated with Levosimendan because of heart failure.

Study population: Children (< 16 years) admitted to the pediatric intensive care unit, with acute or chronic heart failure.

Intervention (if applicable): no intervention Main study parameters/endpoints: The primary endpoint of the study is to describe the pharmacokinetic profile by determining plasma levels of levosimendan and its metabolites during 12 days following a 24-hour infusion in children with heart failure in different age groups. Secondary endpoints are the clinically measured hemodynamic variables (heart rate, bloodpressure, lactate, troponin, pro-BNP, venous saturation) and echocardiographic variables (ejection fraction, shortening fraction, tissue Doppler) of all patients.

• Study Type: Observational
• Enrollment (Anticipated): 36

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands
    • Recruiting
    • PICU Leiden University Medical Center
    • Principal Investigator: Peter P Roeleveld, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

All children admitted to the Pediatric Intensive Care Unit with Acute Heart Failure who will receive Levosimendan as part of their treatment.

Patients will receive Levosimendan whether they participate in the study (sampling levosimendan levels) or not.

Description

Inclusion Criteria:

• All children admitted to the Pediatric Intensive Care Unit with Acute Heart Failure who will receive Levosimendan as part of their treatment.

Exclusion Criteria:

• no informed consent
• no sampling line

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
children > 6 months; children > 6 months of age
children < 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the pharmacokinetic profile of levosimendan and is metabolites	AUC, Cmax, half-life, steady state concentration, plasma clearance, volume of distribution	3 years

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: Orion Corporation, Orion Pharma
• Investigators: Principal Investigator: Peter P Roeleveld, MD, Leiden University Medical Center; Study Chair: Heleen E Bunker-Wiersma, MD, phd, Leiden University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2012
• Primary Completion (Anticipated): September 1, 2019
• Study Completion (Anticipated): September 1, 2019

Study Registration Dates

• First Submitted: May 23, 2012
• First Submitted That Met QC Criteria: October 9, 2012
• First Posted (Estimate): October 11, 2012

Study Record Updates

• Last Update Posted (Actual): August 20, 2019
• Last Update Submitted That Met QC Criteria: August 19, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Children; Pharmacokinetics; Levosimendan
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: ICCE12.001