Dobutamine Versus Placebo for Low Superior Vena Cava Flow in Newborns

Hemodynamic Instability Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01605279
• Other study ID #: NeoDobuta
• Secondary ID: 2009-010901-35
• Status: Completed
• Phase: Phase 2
• First received: May 22, 2012
• Last updated: March 6, 2015
• Start date: September 2010
• Est. completion date: October 2012

Study information

• Verified date: March 2015
• Source: Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 127
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 12 Hours

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hemodynamic Instability

Intervention

Drug:
• Dobutamine
Patients with low SVCF in the first 12 hours of life will be randomized to receive Dobutamine or Placebo. First dose: 5 microg/k/min; second dose: 10 microg/k/min; third dose: 15 microg/k/min; forth dose: 20 microg/k/min. Dobutamine concentration will be prepared in a 20 ml syringe and the dose will be adjusted so each 0.1 ml/kg per hour increase in flow rate would deliver the corresponding step-increase in the drug infusion dose. Dose increments will be 5, 10, 15, 20 microg/kg per minute The study drug was increased in a stepwise manner every 30 minutes until the optimal SVCF was attained and maintained for 60 minutes (SVCF-OP). Treatment duration: 24 hours of postnatal age, maintaining the infusion rate which achieves the SVCF-OP.
• Placebo
Patients with low SVCF in the first 12 hours of life will be randomised to receive Dobutamine or Placebo (dextrose 5% in water, D5W, as Placebo)

Locations

Country	Name	City	State
Spain	La Paz University Hospital	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Adelina Pellicer

Country where clinical trial is conducted

Spain, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Low SVCF prevalence	Low superior vena cava flow (SVCF) prevalence (<40cc/kg/min ) assessed with echocardiography	From birth to the 4th day of postnatal life	No
Secondary	Required dose for achieving SVCF-OP (=40 cc/kg/min)	Required dose of dobutamine for achieving superior vena cava flow optimum (SVCF-OP) that is SVCF =40 cc/kg/min	From birth to the 4th day of postnatal life	No
Secondary	Required dose for achieving SVCF-OP-60 (=40 cc/kg/min maintained during 60 minutes)	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	From birth to the 4th day of postnatal life	No
Secondary	NIRS variables	NIRS variables: TOI (tissue oxygenation index), ?HbT (as a marker of changes in cerebral blood volume, ?DHb (as a marker of changes in cerebral blood flow will be monitored continuously by NIRS.	From birth to 24 hours of life	No
Secondary	Doppler-cranial ultrasonography (PD-CUS) variables.	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.	From birth to the 4th day of postnatal life	No
Secondary	Invasive or non-invasive arterial blood pressure	Invasive or non-invasive arterial blood pressure	From birth to the 4th day of postnatal life	No
Secondary	Central and peripheral temperature	Central and peripheral temperature	From birth to the 4th day of postnatal life	No
Secondary	Heart rate	Heart rate	From birth to the 4th day of postnatal life	No
Secondary	Respiratory rate	Respiratory rate	From birth to the 4th day of postnatal life	No
Secondary	Other echocardiographic variables	Right and left ventricular output; Pulmonary pressure; Patent ductus arteriosus	From birth to the 4th day of postnatal life	No
Secondary	Biochemistry markers	Arterial, venous or capillary gasometry, serum lactate; Hemogram, ions, glycemia, creatinine, proteins, Troponine I, N-terminal probrain natriuretic peptide(NT-proBNP)	From birth to the 4th day of postnatal life	No
Secondary	Structural brain damage markers:	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.	From birth to discharge (approximately around 10-15 weeks)	Yes
Secondary	Mortality and neurodevelopment variables	Mortality rate; Cerebral palsy; Neurodevelopmental delay	From birth until 2 years of corrected age	Yes