Two Inodilators Postsurgery in Neonates

NCT01576094 | Completed Phase 1 DMC

• 1 other identifier: MilevoNeo
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Low Cardiac Output Syndrome

Keywords

congenital heart disease

Outcome Measures

Primary Outcomes (1)

• Perfusion-oxygenation

  Changes in cerebral and thigh oxyhaemoglobin (O2Hb), deoxyhaemoglobin (HHb), total haemoglobin (THb) and tissue oxygenation index (TOI). The cerebral and peripheral intravascular oxygenation as c∆HbD was also assessed.

  NIRS evaluation started immediately after surgery and was maintained during 24 h. At 48 h after surgery, a new NIRS evaluation during 4 hours. At 96 h post-surgery, during 4h.

Secondary Outcomes (11)

• Blood gases

  preoperative (baseline) and then one determination every 6 hours until 24 h post-surgery. One determination at 48h post-surgery. One determination at 96 h post-surgery.

• Blood pressure

  preoperative (baseline) to post-operative day 6.

• temperature

  preoperative (baseline) to post-operative day 6.

• arterial oxygen saturation

  preoperative (baseline) to post-operative day 6.

• cooximetry

  preoperative (baseline) and then one determination every 6 hours until 24 h post-surgery. One determination at 48h post-surgery. One determination at 96 h post-surgery.

Study Arms (2)

Milrinone

ACTIVE COMPARATOR

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

Drug: Milrinone

Levosimendan

ACTIVE COMPARATOR

Drug: Levosimendan

Interventions

Milrinone 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

Also known as: cronotrope

Milrinone

Levosimendan 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.

Also known as: Simdax

Levosimendan

Eligibility Criteria

• Age: Up to 40 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• Parental consent refused
• Inodilators contraindicated

Sponsors & Collaborators

• Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz: lead
• Hospital Universitario La Paz: collaborator
• Fondo de Investigacion Sanitaria: collaborator

Study Sites (1)

Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

Location

Related Publications (1)

• 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.

  PMID: 20881438 BACKGROUND

MeSH Terms

Conditions

Cardiac Output, Low; Heart Defects, Congenital

Interventions

Milrinone; Simendan

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

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

Study Officials

• Adelina Pellicer, PhD

  Dept. of Neonatology, La Paz University Hospital, Madrid

  PRINCIPAL INVESTIGATOR

• Joan Riera, MBE

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

  STUDY CHAIR

• Paloma López, MD

  Dept. of Neonatology, La Paz University Hospital, Madrid

  STUDY CHAIR

• María Carmen Bravo, PhD

  Dept. of Neonatology, La Paz University Hospital, Madrid

  STUDY CHAIR

• Rosario Madero, MD

  Division of Biostatistics, La Paz University Hospital, Madrid

  STUDY CHAIR

• Jesús Pérez-Rodríguez, PhD

  Dept. of Neonatology, La Paz University Hospital, Madrid

  STUDY CHAIR

• Carlos Labrandero, MD

  Dept. Paediatric Cardiology, La Paz University Hospital, Madrid

  STUDY CHAIR

• José Quero, PhD

  Dept. of Neonatology, La Paz University Hospital, Madrid

  STUDY CHAIR

• Antonio Buño, PhD

  Clinical Pathology Service, La Paz University Hospital, Madrid

  STUDY CHAIR

• Luis Castro, MD

  Dept. Paediatric Anaesthesiology, La Paz University Hospital, Madrid

  STUDY CHAIR

• Fernando Cabañas, PhD

  Dept. of Neonatology, La Paz University Hospital, Madrid

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 31, 2012
• First Posted: April 12, 2012
• Study Start: November 1, 2009
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: April 12, 2012

Record last verified: 2012-04

Locations

ES (1)