Two Inodilators Postsurgery in Neonates

NCT ID: NCT01576094

Last Updated: 2012-04-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2010-11-30

Brief 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.

Detailed Description

Surgical repair is the primary therapy for congenital heart defects in the newborn. The neonatal cardiovascular system is at particular risk to develop the surgery-related low cardiac output syndrome (LCOS), thus vasoactive agents are routinely used in the postoperative management. Systematic research on the efficacy of these drugs is scarce in the newborn. As LCOS pathophysiology joints impaired myocardial contractility and the peripheral effects of ischemia/reperfusion injury on the endothelium, early use of inodilators (IND) are strongly recommended to reduce afterload and improve contractility. This study aims to test the equivalence in dose-dependent hemodynamic effects of 2 IND, Milrinone and Levosimendan, used early without loading dose in the preoperative period to prevent LCOS. By means of non-invasive technology the investigators will assess cardiac function (serial structural and functional echocardiography), the cerebral and peripheral perfusion and oxygenation (continuous near-infrared monitoring), cerebral function (continuous amplitude integrated EEG monitoring), will rule out CNS acquired lesions (serial transfontanelar echo-Doppler studies), and will follow up different biochemical markers of myocardial stress and apoptosis. Pharmacokinetic studies will be also performed.

Conditions

Low Cardiac Output Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Milrinone

Milrinone (MR) lactate 1 mg/ml: dose 1, starting immediately after central lines were placed and maintained for the duration of the surgical procedure; dose 2, on NICU admission; dose 3, after 2 hours of stability with dose 2, and maintained up to 48 hours. Accordingly, patients randomised to MR received 0.5 , 0.75 and 1 microg/kg per min

Group Type: ACTIVE_COMPARATOR

Milrinone

Intervention Type: DRUG

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

Levosimendan

Group Type: ACTIVE_COMPARATOR

Levosimendan

Intervention Type: DRUG

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.

Interventions

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

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

cronotrope; Simdax

Eligibility Criteria

Inclusion Criteria

• Newborns undergoing cardiovascular surgery who were in stable pre-operative haemodynamic condition
• Parental consent given

Exclusion Criteria

• Parental consent refused
• Inodilators contraindicated

• Maximum Eligible Age: 40 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital Universitario La Paz

OTHER

Sponsor Role: collaborator

Fondo de Investigacion Sanitaria

OTHER

Sponsor Role: collaborator

Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz

OTHER

Sponsor Role: lead

Responsible Party

Adelina Pellicer

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Adelina Pellicer, PhD

Role: PRINCIPAL_INVESTIGATOR

Dept. of Neonatology, La Paz University Hospital, Madrid

Joan Riera, MBE

Role: STUDY_CHAIR

Bio-Engineer and Nanotechnology Dept., Polytechnic University of Madrid

Paloma López, MD

Role: STUDY_CHAIR

Dept. of Neonatology, La Paz University Hospital, Madrid

María Carmen Bravo, PhD

Role: STUDY_CHAIR

Dept. of Neonatology, La Paz University Hospital, Madrid

Rosario Madero, MD

Role: STUDY_CHAIR

Division of Biostatistics, La Paz University Hospital, Madrid

Jesús Pérez-Rodríguez, PhD

Role: STUDY_CHAIR

Dept. of Neonatology, La Paz University Hospital, Madrid

Carlos Labrandero, MD

Role: STUDY_CHAIR

Dept. Paediatric Cardiology, La Paz University Hospital, Madrid

José Quero, PhD

Role: STUDY_CHAIR

Dept. of Neonatology, La Paz University Hospital, Madrid

Antonio Buño, PhD

Role: STUDY_CHAIR

Clinical Pathology Service, La Paz University Hospital, Madrid

Luis Castro, MD

Role: STUDY_CHAIR

Dept. Paediatric Anaesthesiology, La Paz University Hospital, Madrid

Fernando Cabañas, PhD

Role: STUDY_CHAIR

Dept. of Neonatology, La Paz University Hospital, Madrid

Locations

Hospital Universitario La Paz

Madrid, Madrid, Spain

Countries

Spain

References

Bravo MC, Lopez P, Cabanas F, Perez-Rodriguez J, Perez-Fernandez E, Quero J, Pellicer A. Acute effects of levosimendan on cerebral and systemic perfusion and oxygenation in newborns: an observational study. Neonatology. 2011;99(3):217-23. doi: 10.1159/000314955. Epub 2010 Sep 25.

Reference Type: BACKGROUND

PMID: 20881438 (View on PubMed)

Other Identifiers

MilevoNeo

Identifier Type: -

Identifier Source: org_study_id