Dobutamine Versus Placebo for Low Superior Vena Cava Flow in Newborns - Full Text View

Purpose

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.

Condition	Intervention	Phase
Hemodynamic Instability	Drug: Dobutamine Drug: Placebo	Phase 2

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

Resource links provided by NLM:

Drug Information available for: Dobutamine Dobutamine hydrochloride

U.S. FDA Resources

Further study details as provided by Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz:

Primary Outcome Measures:

Low SVCF prevalence [ Time Frame: From birth to the 4th day of postnatal life ] [ Designated as safety issue: No ]
Low superior vena cava flow (SVCF) prevalence (<40cc/kg/min ) assessed with echocardiography

Secondary Outcome Measures:

Required dose for achieving SVCF-OP (≥40 cc/kg/min) [ Time Frame: From birth to the 4th day of postnatal life ] [ Designated as safety issue: No ]
Required dose of dobutamine for achieving superior vena cava flow optimum (SVCF-OP) that is SVCF ≥40 cc/kg/min
Required dose for achieving SVCF-OP-60 (≥40 cc/kg/min maintained during 60 minutes) [ Time Frame: From birth to the 4th day of postnatal life ] [ Designated as safety issue: No ]
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
NIRS variables [ Time Frame: From birth to 24 hours of life ] [ Designated as safety issue: No ]
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.
Doppler-cranial ultrasonography (PD-CUS) variables. [ Time Frame: From birth to the 4th day of postnatal life ] [ Designated as safety issue: No ]
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 [ Time Frame: From birth to the 4th day of postnatal life ] [ Designated as safety issue: No ]
Invasive or non-invasive arterial blood pressure
Central and peripheral temperature [ Time Frame: From birth to the 4th day of postnatal life ] [ Designated as safety issue: No ]
Central and peripheral temperature
Heart rate [ Time Frame: From birth to the 4th day of postnatal life ] [ Designated as safety issue: No ]
Heart rate
Respiratory rate [ Time Frame: From birth to the 4th day of postnatal life ] [ Designated as safety issue: No ]
Respiratory rate
Other echocardiographic variables [ Time Frame: From birth to the 4th day of postnatal life ] [ Designated as safety issue: No ]
- Right and left ventricular output
- Pulmonary pressure
- Patent ductus arteriosus
Biochemistry markers [ Time Frame: From birth to the 4th day of postnatal life ] [ Designated as safety issue: No ]
- Arterial, venous or capillary gasometry, serum lactate
- Hemogram, ions, glycemia, creatinine, proteins, Troponine I, N-terminal probrain natriuretic peptide(NT-proBNP)
Structural brain damage markers: [ Time Frame: From birth to discharge (approximately around 10-15 weeks) ] [ Designated as safety issue: Yes ]
- 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.
Mortality and neurodevelopment variables [ Time Frame: From birth until 2 years of corrected age ] [ Designated as safety issue: Yes ]
- Mortality rate
- Cerebral palsy
- Neurodevelopmental delay

Estimated Enrollment:	130
Study Start Date:	September 2010
Estimated Study Completion Date:	September 2012
Estimated Primary Completion Date:	September 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Dobutamine Patients with low SVCF in the first 12 hours of life will be randomised to receive dobutamine or placebo.	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. Other Name: DB
Placebo Comparator: Placebo Patients with low SVCF in the first 12 hours of life will be randomised to receive Dobutamine or Placebo.	Drug: 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) Other Name: PL

Arms

Assigned Interventions

Experimental: Dobutamine

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

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.

Other Name: DB

Placebo Comparator: Placebo

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

Drug: 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)

Other Name: PL

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

Ages Eligible for Study:	up to 12 Hours
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01605279

Contacts

Contact: María Carmen Bravo, PhDMD	+34917277373	m.bravo.laguna@gmail.com
Contact: Adelina Pellicer, PhDMD	+34917277373	apellicer.hulp@salud.madrid.org

Locations

Spain
La Paz University Hospital	Recruiting
Madrid, Spain, 28046
Contact: María Carmen Bravo, PhDMD +34917277373 ext 47373 m.bravo.laguna@gmail.com
Contact: Adelina Pellicer, PhDMD +34917277373 ext 47373 apellicer.hulp@salud.madrid.org
Principal Investigator: María Carmen Bravo, PhDMD
Sub-Investigator: Fernando Cabañas, PhDMD
Sub-Investigator: Adelina Pellicer, PhDMD
Sub-Investigator: Joan Riera
Sub-Investigator: Paloma López, MD
Sub-Investigator: Laura Sánchez, MD
Sub-Investigator: Jesús Pérez-Rodríguez, PhDMD
Sub-Investigator: José Quero, PhDMD
Sub-Investigator: Rosario Madero, PhDMD
Sub-Investigator: Antonio Buño, PhDMD

Sponsors and Collaborators

Maria Carmen Bravo Laguna

Investigators

Principal Investigator:

María Carmen Bravo, PhDMD

Fundación Investigación Biomédica HULP

More Information

Publications:

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.

Responsible Party:	Maria Carmen Bravo Laguna, Principal investigator, Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz
ClinicalTrials.gov Identifier:	NCT01605279 History of Changes
Other Study ID Numbers:	NeoDobuta, 2009-010901-35
Study First Received:	May 22, 2012
Last Updated:	May 23, 2012
Health Authority:	Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz:

Low superior vena cava flow
Functional echocardiography

Additional relevant MeSH terms:

Dobutamine
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents

Physiological Effects of Drugs
Adrenergic beta-1 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents

ClinicalTrials.gov processed this record on June 18, 2013