Hypotension | Treatment of Hypotension of Prematurity (TOHOP)
Hypotension research study
What is the primary objective of this study?
Hypotension in the very preterm infant (gestational age [GA] <32 wks) is a frequently occurring clinical problem. Although no real consensus has been reached on the definition of hypotension in these infants, in clinical practice a mean blood pressure (mean BP) in mmHg lower than the GA age in weeks is considered to be the starting point for anti-hypotensive therapy. However, although an association between neonatal hypotension and mortality/ morbidity exists, there is no evidence of causality between hypotension (meanBP <GA in completed weeks) and neonatal mortality/morbidity. In addition, using mean BP alone as the indication of treatment of neonatal cardiovascular compromise without taking into consideration the status of tissue perfusion may lead to unnecessary exposure of neonates to vasoactive medication. This medication can be potentially harmful to these extremely vulnerable patients. The aim of this study is to compare neonatal mortality and short-term neurodevelopmental outcome (cerebral ultrasound during the first 7 days of life, advanced MRI indices of structural brain injury at term GA) and long-term neurodevelopmental outcomes (Bayley scales of infant development III [BSID-III] at 24 months) between two groups of very preterm infants presenting with hypotension without clinical and laboratory evidence of compromised tissue perfusion during the first 3 days of life. Hypotension will be defined as the mean BP (in mm Hg) lower than the infant's GA (in weeks). Patients randomized to \"Group A\" will be treated according to the treatment protocol operative in the Neonatal Intensive Care Unit (NICU) of the University Medical Centre Utrecht (UMCU) while \"Group B\" will receive no cardiovascular support for hypotension unless they have evidence of compromised tissue perfusion and end-organ function ((i.e. near infrared-monitored regional cerebral oxygen saturation (ScO2) <50% despite optimized ventilatory support and FiO2 administration, plasma lactate >6 mmol/L; and/or urine output <0.6 mL/kg/hour) or mean BP >5mmHg lower than the current guideline. The investigators hypothesize that there will be no differences between the two groups concerning short and long-term neurodevelopmental outcomes.
Who is eligible to participate?
Inclusion Criteria: - Idiopathic arterial hypotension as defined by a mean BP in mmHg less than the GA in weeks at birth. - Written parental consent Exclusion Criteria: - Prior inclusion indirect clinical or direct laboratory evidence of poor organ/tissue perfusion (plasma lactate >6 mmol/L on two consecutive measurements and/or urine production <0.6 mL/kg/h for a 6-hour period - Clinically and/or microbiologically proven sepsis - Major congenital abnormalities - Postnatal age at the time of the development of systemic hypotension >72 hours - No arterial line for continuously monitoring of blood pressure
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Other:Anti-hypotensive treatmentHypotension is managed using a variety of treatment options. Options include: fluid bolus(es), dopamine, dobutamine, hydrocortisone and epinephrine.
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
Standard careInfants will be treated according to the treatment policy operative in the Neonatal Intensive Care Unit (NICU) of the Wilhelmina Children's Hospital/University Medical Centre Utrecht (UMCU): anti-hypotensive therapy will be started when the mean blood pressure (in mmHg) is below the gestational age in weeks.
Delayed interventionAnti hypotensive therapy will be started when the mean blood pressure (in mmHg) is < (gestational age in weeks - 5 mmHg) or when there is clinical or biochemical evidence of impaired tissue perfusion.
Start Date: September 2011
Completed Date: September 2016
Primary Outcome: Neurodevelopmental outcome assessment using the Bayley Scales of Infant Development III
Secondary Outcome: Incidence of peri-intraventricular haemorrhage
Study sponsors, principal investigator, and references
Principal Investigator: Petra MA Lemmers, MD, PhD
Lead Sponsor: UMC Utrecht