Treatment of Hypotension of Prematurity (TOHOP)

Summary

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.

Conditions

• Hypotension

Interventions

OTHER

Anti-hypotensive treatment

Hypotension is managed using a variety of treatment options. Options include: fluid bolus(es), dopamine, dobutamine, hydrocortisone and epinephrine.

Sponsors & Collaborators

• UMC Utrecht

  lead OTHER

Principal Investigators

• Petra MA Lemmers, MD, PhD · UMC Utrecht

• Thomas Alderliesten, MD · UMC Utrecht

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

24 Weeks

Max Age

30 Weeks

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-09-01

Primary Completion

2021-02-01

Completion

2021-02-01

Countries

• Netherlands

Study Locations