Dobutamine Versus Placebo for Low Superior Vena Cava Flow in Newborns

Phase 2

Completed

• Conditions: Hemodynamic Instability
• Interventions: Drug: Placebo; Drug: Dobutamine

• Registration Number: NCT01605279
• Lead Sponsor: Adelina Pellicer

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.

Study Timeline

• Study Start: 2010-09
• Study First Submitted: 2012-05-22
• Study First Submitted QC: 2012-05-23
• Study First Posted: 2012-05-24
• Primary Completion: 2012-10
• Study Completion: 2012-10
• Status Verified: 2015-03
• Last Update Submitted: 2015-03-06
• Last Update Posted: 2015-03-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 127

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Patients with low SVCF in the first 12 hours of life will be randomised to receive Dobutamine or Placebo.
Dobutamine	Dobutamine	Patients with low SVCF in the first 12 hours of life will be randomised to receive dobutamine or placebo.

Primary Outcome Measures

Name	Time	Method
Low SVCF prevalence	From birth to the 4th day of postnatal life	Low superior vena cava flow (SVCF) prevalence (\<40cc/kg/min ) assessed with echocardiography

Secondary Outcome Measures

Name	Time	Method
Mortality and neurodevelopment variables	From birth until 2 years of corrected age	* Mortality rate; * Cerebral palsy; * Neurodevelopmental delay
Required dose for achieving SVCF-OP-60 (≥40 cc/kg/min maintained during 60 minutes)	From birth to the 4th day of postnatal life	Required dose of dobutamine for achieving superior vena cava flow optimum for 60 min (SVCF-OP-60), that is SVCF ≥40 cc/kg/min maintained during 60 minutes
Doppler-cranial ultrasonography (PD-CUS) variables.	From birth to the 4th day of postnatal life	Doppler-cranial ultrasonography (PD-CUS) variables. Changes in cerebral blood flow velocities and the resistance index in cerebral arteries will be evaluated. The effect of SVCF changes on these variables will be analysed.
Invasive or non-invasive arterial blood pressure	From birth to the 4th day of postnatal life	Invasive or non-invasive arterial blood pressure
Respiratory rate	From birth to the 4th day of postnatal life	Respiratory rate
Other echocardiographic variables	From birth to the 4th day of postnatal life	* Right and left ventricular output; * Pulmonary pressure; * Patent ductus arteriosus
Biochemistry markers	From birth to the 4th day of postnatal life	* Arterial, venous or capillary gasometry, serum lactate; * Hemogram, ions, glycemia, creatinine, proteins, Troponine I, N-terminal probrain natriuretic peptide(NT-proBNP)
NIRS variables	From birth to 24 hours of life	NIRS variables: TOI (tissue oxygenation index), ∆HbT (as a marker of changes in cerebral blood volume, ΔDHb (as a marker of changes in cerebral blood flow will be monitored continuously by NIRS.
Heart rate	From birth to the 4th day of postnatal life	Heart rate
Required dose for achieving SVCF-OP (≥40 cc/kg/min)	From birth to the 4th day of postnatal life	Required dose of dobutamine for achieving superior vena cava flow optimum (SVCF-OP) that is SVCF ≥40 cc/kg/min
Central and peripheral temperature	From birth to the 4th day of postnatal life	Central and peripheral temperature
Structural brain damage markers:	From birth to discharge (approximately around 10-15 weeks)	* Intraventricular hemorrhage (IVH) grade 1.; * IVH grade 2.; * IVH grade 3.; * Periventricular hemorrhagic infarction.; * Moderate or severe periventricular echogenicity.; * Persistent periventricular echogenicity.; * Cyst periventricular echogenicity.

Trial Locations

Locations (1)

La Paz University Hospital; 🇪🇸 Madrid, Spain