Levosimendan Pharmacokinetics in Children

NCT ID: NCT01704131

Last Updated: 2019-08-20

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 36 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2019-09-01

Brief Summary

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.

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.

Conditions

Acute Heart Failure

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

children > 6 months

children \> 6 months of age

No interventions assigned to this group

children < 6 months

children \< 6 months

No interventions assigned to this group

Eligibility Criteria

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

• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Orion Corporation, Orion Pharma

INDUSTRY

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Peter Paul Roeleveld

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Peter P Roeleveld, MD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Heleen E Bunker-Wiersma, MD, phd

Role: STUDY_CHAIR

Leiden University Medical Center

Locations

PICU Leiden University Medical Center

Leiden, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Peter P Roeleveld, MD

Role: CONTACT

p.p.roeleveld@lumc.nl

+31715261677 ext. 8486

H E Bunker-Wiersma, MD, Phd

Role: CONTACT

H.E.Bunker-Wiersma@lumc.nl

+31715261677 ext. 8775

Other Identifiers

ICCE12.001

Identifier Type: -

Identifier Source: org_study_id