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Treatment of Hypotension of Prematurity (TOHOP)

This study is currently recruiting participants.
Verified September 2011 by UMC Utrecht
Sponsor:
Information provided by (Responsible Party):
Petra Lemmers, UMC Utrecht
ClinicalTrials.gov Identifier:
NCT01434251
First received: September 9, 2011
Last updated: September 13, 2011
Last verified: September 2011
History of Changes
  Purpose

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.


Condition Intervention
Hypotension
 Other: Anti-hypotensive treatment

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treatment of Hypotension of Prematurity: a Randomized, Non-blinded Cohort Clinical Trial

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by UMC Utrecht:

Primary Outcome Measures:
  • Neurodevelopmental outcome assessment using the Bayley Scales of Infant Development III [ Time Frame: 24 months postnatal age. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of peri-intraventricular haemorrhage [ Time Frame: first 7 postnatal days. ] [ Designated as safety issue: Yes ]
    As detected by cranial ultrasound

  • Incidence of white matter injury and gray matter injury [ Time Frame: adjusted postmenstrual age of 40 weeks ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 150
Study Start Date: September 2011
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard care
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
Hypotension is managed using a variety of treatment options. Options include: fluid bolus(es), dopamine, dobutamine, hydrocortisone and epinephrine.
Delayed intervention
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
Hypotension is managed using a variety of treatment options. Options include: fluid bolus(es), dopamine, dobutamine, hydrocortisone and epinephrine.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   24 Weeks to 30 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  • Intrauterine exposure to excessive maternal vasoactive medication (i.v. use of labetolol)
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01434251

Contacts
Contact: Petra MA Lemmers, MD, PhD +31(0)887555555 ext 5447 p.lemmers@umcutrecht.nl
Contact: Thomas Alderliesten, MD +31(0)887555555 ext 4639 t.alderliesten-2@umcutrecht.nl

Locations
Netherlands
Wilhemlina Childrens Hostpital/University Medical Center Utrecht Recruiting
Utrecht, Netherlands, 3584 EA
Contact: Petra MA Lemmers, MD, PhD     +31(0)887555555 ext 5447     p.lemmers@umcutrecht.nl    
Contact: Thomas Alderliesten, MD     +31(0)887555555 ext 4639     t.alderliesten-2@umcutrecht.nl    
Principal Investigator: Petra MA Lemmers, MD, PhD            
Principal Investigator: Thomas Alderliesten, MD            
Sponsors and Collaborators
UMC Utrecht
Investigators
Principal Investigator: Petra MA Lemmers, MD, PhD UMC Utrecht
Principal Investigator: Thomas Alderliesten, MD UMC Utrecht
  More Information

No publications provided

Responsible Party: Petra Lemmers, MD PhD, UMC Utrecht
ClinicalTrials.gov Identifier: NCT01434251     History of Changes
Other Study ID Numbers: NL 33865.041.10
Study First Received: September 9, 2011
Last Updated: September 13, 2011
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by UMC Utrecht:
Hypotension
premature infants
near infrared spectroscopy

Additional relevant MeSH terms:
Hypotension
Vascular Diseases
Cardiovascular Diseases
Antihypertensive Agents
 Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013