Two Inodilators Postsurgery in Neonates

Summary

Congenital heart defects are the most prevalent group of congenital malformations in newborns. Surgery-related low cardiac output syndrome (LCOS) could be one of the reason for the unfavourable outcome of this population. The early use of inodilators (INDs), specifically milrinone (MR), is proposed to reduce afterload and increase inotropism. Studies in the paediatric population appear to support a clinical usefulness of MR similar to that observed in adults. Levosimendan (LEVO) is a novel class IND developed for the treatment of heart failure. Experience with LEVO in paediatric patients is scarce. The purpose of this study was to systematically test the efficacy and safety of milrinone (MR) and levosimendan (LEVO) in newborns undergoing cardiovascular surgery with cardiopulmonary bypass (CPB). Given the uncertainty about LEVO pharmacokinetics in neonates, the study was designed as a pilot, phase I feasibility study.

Conditions

• Low Cardiac Output Syndrome

Interventions

DRUG

Milrinone

Before surgery, patients received milrinone (MR) (milrinone lactate 1 mg/ml). Intravenous continuous infusion of the study drug through a separate central line started intraoperatively and was increased step-wise at predefined time points: dose 1, starting immediately after central lines were placed and maintained for the duration of the surgical procedure; dose 2, on NICU admission providing the patient was in stable haemodynamic condition; dose 3, starting after 2 hours of stability with dose 2, and maintained up to 48 hours IND infusion started. Accordingly, patients randomised to MR received 0.5 , 0.75 and 1 microg/kg per min

DRUG

Levosimendan

Before surgery patients received levosimendan (levosimendan 2.5 mg/ml). Intravenous continuous infusion of the study drug through a separate central line started intraoperatively and was increased step-wise at predefined time points: dose 1, starting immediately after central lines were placed and maintained for the duration of the surgical procedure; dose 2, on NICU admission providing the patient was in stable haemodynamic condition; dose 3, starting after 2 hours of stability with dose 2, and maintained up to 48 hours IND infusion started. Accordingly, patients randomised to LEVO received 0.1 , 0.15 and 0.2 microg/kg per min, for doses 1, 2 and 3, respectively.

Sponsors & Collaborators

• Hospital Universitario La Paz

  collaborator OTHER

• Fondo de Investigacion Sanitaria

  collaborator OTHER

• Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz

  lead OTHER

Principal Investigators

• Adelina Pellicer, PhD · Dept. of Neonatology, La Paz University Hospital, Madrid

• Joan Riera, MBE · Bio-Engineer and Nanotechnology Dept., Polytechnic University of Madrid

• Paloma López, MD · Dept. of Neonatology, La Paz University Hospital, Madrid

• María Carmen Bravo, PhD · Dept. of Neonatology, La Paz University Hospital, Madrid

• Rosario Madero, MD · Division of Biostatistics, La Paz University Hospital, Madrid

• Jesús Pérez-Rodríguez, PhD · Dept. of Neonatology, La Paz University Hospital, Madrid

• Carlos Labrandero, MD · Dept. Paediatric Cardiology, La Paz University Hospital, Madrid

• José Quero, PhD · Dept. of Neonatology, La Paz University Hospital, Madrid

• Antonio Buño, PhD · Clinical Pathology Service, La Paz University Hospital, Madrid

• Luis Castro, MD · Dept. Paediatric Anaesthesiology, La Paz University Hospital, Madrid

• Fernando Cabañas, PhD · Dept. of Neonatology, La Paz University Hospital, Madrid

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Max Age

40 Days

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-11-30

Primary Completion

2010-11-30

Completion

2010-11-30

Countries

• Spain

Study Locations