Levosimendan Administration in Neonates With Transposition of the Great Arteries

Perioperative Levosimendan Administration in Neonates With Transposition of the Great Arteries: Randomized Controlled Trial

Calcium sensitizer drugs such as Levosimendan may exert anti-ischemic effect in addition to positive inotropic and anti-stunning effects mediated by the opening of ATP-sensitive potassium (KATP) channels. The aim of the study is to test the myocardial protection effect of peri-operative iv infusion of Levosimendan in a cohort of neonates affected by transposition of the great arteries undergoing surgical correction by arterial switch.

Study Overview

• Status: Completed
• Conditions: Low Cardiac Output Syndrome
• Intervention / Treatment: Drug: levosimendan; Drug: placebo

Detailed Description

Function of the myocardium of neonates with congenital heart disease may be affected by several factors in post operative phase: congenital insufficiency, cardiopulmonary bypass low perfusion, ischemima during the cross-clamp phase, low cardiac output syndrome, systemic inflammation. Furthermore, neonates have immature molecular mechanisms leading to calcium utilization inside myocytes. Calcium sensitizer drugs such as Levosimendan may exert anti-ischemic effect in addition to positive inotropic and anti-stunning effects mediated by the opening of ATP-sensitive potassium (KATP) channels. The aim of the study is to test the inodilator and myocardial protection effect of peri-operative iv infusion of 0.1 mcg/kg/min Levosimendan (without previuos bolus) in a cohort of neonates affected by transposition of the great arteries undergoing surgical correction by arterial switch.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00165
    • Bambino Gesu Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 1 month (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• neonates affected by transposition of the great arteries scheduled to elective surgery

Exclusion Criteria:

• neonates affected by transposition of the great arteries who are not scheduled to elective surgery (urgent procedures, patients older than 30 days)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: levosimendan; levosimendan continuous infusion at a rate of 0.1 mcg/kg<min	Drug: levosimendan; patients enrolled in this group will receive a levosimendan continuous infusion at a rate of 0.1 mcg/kg/min; Other Names: simdax; Drug: placebo; saline continuous infusion; Other Names: saline
Placebo Comparator: placebo; saline infusion	Drug: levosimendan; patients enrolled in this group will receive a levosimendan continuous infusion at a rate of 0.1 mcg/kg/min; Other Names: simdax; Drug: placebo; saline continuous infusion; Other Names: saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
lower inotropic score in the levosimendan group	inotropic score will be calculated as: dopamine (mcg/Kg/min) * 1 + milrinone (mcg/Kg/min) * 15 + epinephrine (mcg/Kg/min) * 100.	Time points: from T0 (within 1 hour of intensive care unit admission) to T7 (72nd post operative hour) through T2, T3, T4, T5, T6, T7)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Low cardiac output syndrome (LCOS) incidence reduction in the treatment group	LCOS will be estimated by the analysis of average heart rate, mean arterial pressure, left atrial pressure, lactates and pH during the evaluated time frame	Time points: from T0 (within 1 hour of intensive care unit admission) to T7 (72nd post operative hour) through T2, T3, T4, T5, T6, T7)

Collaborators and Investigators

• Sponsor: Bambino Gesù Hospital and Research Institute
• Investigators: Study Director: Sergio Picardo, MD, Head, Bambino Gesu Hospital

Publications and helpful links

General Publications

• Di Chiara L, Ricci Z, Garisto C, Morelli S, Giorni C, Vitale V, Di Donato RM, Picardo S. Initial experience with levosimendan infusion for preoperative management of hypoplastic left heart syndrome. Pediatr Cardiol. 2010 Jan;31(1):166-7. doi: 10.1007/s00246-009-9571-6. No abstract available.
• Osthaus WA, Boethig D, Winterhalter M, Huber D, Goerler H, Sasse M, Sumpelmann R. First experiences with intraoperative Levosimendan in pediatric cardiac surgery. Eur J Pediatr. 2009 Jun;168(6):735-40. doi: 10.1007/s00431-008-0834-7. Epub 2008 Sep 24.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: May 6, 2010
• First Submitted That Met QC Criteria: May 7, 2010
• First Posted (Estimate): May 10, 2010

Study Record Updates

• Last Update Posted (Estimate): June 26, 2012
• Last Update Submitted That Met QC Criteria: June 22, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: levosimendan; pediatric cardiac surgery; low cardiac output syndrome; transposition of the great arteries
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Heart Defects, Congenital; Cardiovascular Abnormalities; Transposition of Great Vessels; Cardiac Output, Low; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Simendan
• Other Study ID Numbers: levoTGA1