Clinical Trial: Treatment of Hypotension of Prematurity (TOHOP)

Study Status: Recruiting
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Treatment of Hypotension of Prematurity: a Randomized, Non-blinded Cohort Clinical Trial

Brief 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 cereb

Detailed Summary:

Rationale: Hypotension in the very preterm infant (gestational age [GA] <32wks) is a frequently occurring clinical problem. Although no real consensus has been reached on the definition of hypotension in the very preterm baby, in clinical practice a mean blood pressure (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 and morbidity exists, there is no evidence of causation between hypotension and neonatal mortality and morbidity (including neurodevelopmental outcome at 2 and 3 years of age). In addition, using mean BP alone as the indication of treatment of neonatal cardiovascular compromise without taking into consideration information on the status of tissue perfusion may lead to unnecessary exposure of neonates to forceful vasoactive medications potentially causing harm to these extremely vulnerable patients.

Objective: To compare neonatal mortality and short-term (advanced MRI indices of structural brain injury at 40 weeks' 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 72 postnatal hours (3 days). 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 policy operative in the Neonatal Intensive Care Unit (NICU) of the Wilhelmina Children's Hospital/University Medical Centre Utrecht (UMCU) while "Group B" will receive no cardiovascular support for hypotension unless they have a mean BP lower than the current limit minus 5 mmHg and/or evidence of compromised tissue perfusion an
Sponsor: UMC Utrecht

Current Primary Outcome: Neurodevelopmental outcome assessment using the Bayley Scales of Infant Development III [ Time Frame: 24 months postnatal age. ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Incidence of peri-intraventricular haemorrhage [ Time Frame: first 7 postnatal days. ]
    As detected by cranial ultrasound
  • Incidence of white matter injury and gray matter injury [ Time Frame: adjusted postmenstrual age of 40 weeks ]
    White/gray matter injury assessed by using advanced MRI indices.
  • Difference in the ability to maintain cerebral blood flow autoregulation [ Time Frame: Determined from start of hypotensive period (expected within 24h postnatal age) until end of hypotensive period (expected average of 72h postnatal age) ]
    Assessed by determining the correlation between the mean arterial blood pressure and cerebral oxygenation (rScO2).
  • Mortality [ Time Frame: Duration of follow-up (24 months postnatal age) ]


Original Secondary Outcome: Same as current

Information By: UMC Utrecht

Dates:
Date Received: September 9, 2011
Date Started: September 2011
Date Completion: September 2016
Last Updated: May 26, 2015
Last Verified: May 2015