Treatment of Hypotension of Prematurity (TOHOP)

NCT01434251 | Terminated DMC

• 1 other identifier: NL 33865.041.10
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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 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

Keywords

Hypotension; premature infants; near infrared spectroscopy

Outcome Measures

Primary Outcomes (1)

• Neurodevelopmental outcome assessment using the Bayley Scales of Infant Development III

  24 months postnatal age.

Secondary Outcomes (4)

• Incidence of peri-intraventricular haemorrhage

  first 7 postnatal days.

• Incidence of white matter injury and gray matter injury

  adjusted postmenstrual age of 40 weeks

• Difference in the ability to maintain cerebral blood flow autoregulation

  Determined from start of hypotensive period (expected within 24h postnatal age) until end of hypotensive period (expected average of 72h postnatal age)

• Mortality

  Duration of follow-up (24 months postnatal age)

Study Arms (2)

Standard care

ACTIVE COMPARATOR

Infants 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.

Other: Anti-hypotensive treatment

Delayed intervention

OTHER

Anti 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.

Other: Anti-hypotensive treatment

Interventions

Anti-hypotensive treatment OTHER

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

Delayed intervention; Standard care

Eligibility Criteria

• Age: 24 Weeks - 30 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Idiopathic arterial hypotension as defined by a mean BP in mmHg less than the GA in weeks at birth.
• Written parental consent

You may not qualify if:

• 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

Sponsors & Collaborators

• UMC Utrecht: lead

Study Sites (1)

Wilhemlina Childrens Hostpital/University Medical Center Utrecht

Utrecht, Utrecht, 3584 EA, Netherlands

Location

Related Publications (1)

• Alderliesten T, Arasteh E, van Alphen A, Groenendaal F, Dudink J, Benders MJ, van Bel F, Lemmers P. Treatment of Hypotension of Prematurity: a randomised trial. Arch Dis Child Fetal Neonatal Ed. 2025 Dec 15;111(1):F60-F66. doi: 10.1136/archdischild-2024-328253.

  PMID: 40413017 DERIVED

MeSH Terms

Conditions

Hypotension; Premature Birth

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Petra MA Lemmers, MD, PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

• Thomas Alderliesten, MD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: September 9, 2011
• First Posted: September 14, 2011
• Study Start: September 1, 2011
• Primary Completion: February 1, 2021
• Study Completion: February 1, 2021
• Last Updated: December 16, 2024

Record last verified: 2024-12

Locations

NL (1)