Clinical trial NCT01605279: Dobutamine Versus Placebo for Low Superior Vena Cava Flow in Newborns
Official title: Randomised Double Blind Clinical Trial of Dobutamine Versus Placebo for Low Superior Vena Cava Flow Treatment in Low Birth Weight Infants: Systematic Assessment of Cerebral and Systemic Hemodynamics Effects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hemodynamic Instability
Keywords: Low superior vena cava flow
Functional echocardiography
Lead sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz
Sponsor class: OTHER
First posted: 2012-05-24
Enrollment: 127
Sex: ALL
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Low systemic flow as measured by Doppler-echocardiography has been associated with poor neurological outcome. Yet, it has not been systematically evaluated whether the treatment of this hemodynamic condition is beneficial or not. This study aims to evaluate if treating low systemic flow in preterm infants with dobutamine has any effect on the cerebral circulation and in newborn prognosis.

Detailed description: While rates of survival for very preterm infants are increasing, a significant number of these patients suffer from neurodevelopmental disabilities. The pathophysiology of brain injury in the preterm infant is unclear, although haemodynamic disturbances during the period of transitional circulation after birth leading to ischemia-reperfusion events seem to play an important role. Up to one third of infants born under 30 weeks of gestation develop low systemic flow as measured by Doppler-echocardiography (low superior vena cava flow, SVCF); this finding has been associated with poor neurological outcome. Yet, it has not been systematically evaluated whether the treatment of this hemodynamic condition is beneficial or not. This study aims to evaluate if treating low systemic flow in preterm infants with dobutamina, DB, (inotrope-sympathicomimetic drug) has any effect on the cerebral circulation; specific interest of our research would be to target DB dose for individual patient´s response. Secondly, by means of two non-invasive technologies (cerebral and cardiac ultrasonography-Doppler and near infrared spectroscopy, NIRS), the investigators search to characterise eventual differences in brain perfusion patterns during the adaptation to the transitional circulation that might be associated with the development of brain injury in the most vulnerable population.

Eligibility criteria: Inclusion criteria

* Newborn infants born at ≤ 28 weeks of gestational age.
* Newborn infants born at \> 28 weeks of gestational age and ≤ 30 weeks of gestational age with moderate-severe respiratory distress syndrome, defined as the necessity of respiratory support with a mean pressure ≥ 4 cm H2O or FiO2 ≥ 0.3
* Admission at the NICU in the first 6 hours of life
* Inotrope treatment absent
* Inform consent signed

Exclusion criteria

* Early systemic hypotension, defined as a mean arterial pressure (MAP) lower than the gestational age, during at least 60 minutes and maintained after volume infusion
* Major congenital malformation
* Informed consent declined

Primary outcomes:
measure: Low SVCF prevalence
timeFrame: From birth to the 4th day of postnatal life
Secondary outcomes:
measure: Required dose for achieving SVCF-OP (≥40 cc/kg/min)
timeFrame: From birth to the 4th day of postnatal life
measure: Required dose for achieving SVCF-OP-60 (≥40 cc/kg/min maintained during 60 minutes)
timeFrame: From birth to the 4th day of postnatal life
measure: NIRS variables
timeFrame: From birth to 24 hours of life
measure: Doppler-cranial ultrasonography (PD-CUS) variables.
timeFrame: From birth to the 4th day of postnatal life
measure: Invasive or non-invasive arterial blood pressure
timeFrame: From birth to the 4th day of postnatal life
measure: Central and peripheral temperature
timeFrame: From birth to the 4th day of postnatal life
measure: Heart rate
timeFrame: From birth to the 4th day of postnatal life
measure: Respiratory rate
timeFrame: From birth to the 4th day of postnatal life
measure: Other echocardiographic variables
timeFrame: From birth to the 4th day of postnatal life
measure: Biochemistry markers
timeFrame: From birth to the 4th day of postnatal life
measure: Structural brain damage markers:
timeFrame: From birth to discharge (approximately around 10-15 weeks)
measure: Mortality and neurodevelopment variables
timeFrame: From birth until 2 years of corrected age
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: La Paz University Hospital
Study officials:
affiliation: Fundación Investigación Biomédica HULP
name: María Carmen Bravo, PhDMD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Osborn DA, Evans N, Kluckow M, Bowen JR, Rieger I. Low superior vena cava flow and effect of inotropes on neurodevelopment to 3 years in preterm infants. Pediatrics. 2007 Aug;120(2):372-80. doi: 10.1542/peds.2006-3398.
citation: Bravo MC, Lopez-Ortego P, Sanchez L, Riera J, Madero R, Cabanas F, Pellicer A. Randomized, Placebo-Controlled Trial of Dobutamine for Low Superior Vena Cava Flow in Infants. J Pediatr. 2015 Sep;167(3):572-8.e1-2. doi: 10.1016/j.jpeds.2015.05.037. Epub 2015 Jun 24.