SafeBoosC - a Phase II Trial

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gorm Greisen, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT01590316
First received: May 1, 2012
Last updated: February 3, 2014
Last verified: February 2014
  Purpose

Background 25,000 infants are born extremely preterm every year in Europe. This group of infants carries a high risk of death and subsequent cerebral impairment for the infant, especially in the first 72 hours of life. Mortality is about 20%, and about 25% of survivors live with either cerebral palsy or low intelligence quotient. Preventative measures are keys to reducing mortality and morbidity in this population. There is evidence that the cerebral oxygenation time spent out of range (time with hypoxia or hyperoxia) is associated with poor outcome in infants. Near-infrared spectroscopy (NIRS) has been used to monitor tissue oxygenation since the mid-1980s, and quantification of oxygenation (rStO2) in a percentage from 0 to 100% has been possible for 10 years. From almost 400 preterm infants normal ranges of rStO2 has been determined to be from 55% to 85%. Still, there are no clinical trials and thus no solid evidence of the clinical utility of NIRS in preterm infants. Thus, research on the benefits and harms of cerebral monitoring using NIRS as a part of clinical management of premature infants is much needed.

Objectives The primary objective of the SafeBoosC trial is to examine if it is possible to stabilise the cerebral oxygenation of extremely preterm infants during the first 72 hours of life through the application of cerebral NIRS oximetry and implementation of an rStO2-specific clinical treatment guideline. We hypothesise that by using the specified treatment guideline to respond to cerebral monitoring readings outside the target range, we would reduce the burden of hypo- and hyperoxia and consequently reduce brain injury.

Trial design This is an investigator-initiated randomised, blinded, multinational, phase II feasibility clinical trial involving preterm infants from 12 European countries.

Inclusion criteria The inclusion criteria are: neonates born more than 12 weeks preterm (gestational age up to 27 weeks and 6 days); decision to conduct full life support; parental informed consent; and cerebral NIRS oximeter placed within 3 hours after birth.

Sample size With a 50% reduction of the area outside the normal range of oxygenation in %hours in the experimental group compared to the control group as the minimal clinically significant difference, a standard deviation of the area outside the normal range of 83.2 %hours, a type I error (alpha) of 5%, and a type II error of 0.05 (power of 95%) inclusion of 75 preterm infants in the experimental group and 75 preterm infants in the control group is required. The inclusion of twins are likely to decrease power, so it has been decided to increase sample size to 165 on a pragmatic basis of estimating intracluster correlation, control event rate, and incidence of twin births.

Intervention The premature infants will be randomised into one of two groups (experimental or control). Common is that both groups will have a cerebral oximeter monitoring device placed within three hours after birth. In the experimental group, the cerebral oxygenation reading is visible, and the infant will be treated accordingly using a defined treatment guideline. In the control group, the cerebral oxygenation reading is NOT visible, and the infant will be treated as usual.

Trial duration Monitoring by cerebral oximeter will be started as soon as possible and within 3 hours after birth and the intervention will last for 72 hours. Thereafter, each neonate will be followed up at term date (approximately three months after birth) and at 24 months after term date.

Outcome measures The primary outcome is the burden of hypo- and hyperoxia in %hours during the first 72 hours after birth. The secondary outcomes are brain activity on an amplitude-integrated electroencephalogram (aEEG), blood biomarkers (brain fatty acid binding protein (BFABP), neuroketal, and S100β), serious adverse reactions (SARs), severe brain injury, and all cause mortality at term date (approximately three months after birth). The exploratory outcomes are burden of hypoxia, burden of hyperoxia, neonatal morbidities, brain injury score on magnetic resonance imaging (MRI), number of therapies implemented during the intervention, physiological variables (mean blood pressure (BP), pulse oximeter oxygen saturation (SpO2), and partial pressure of carbon dioxide (pCO2)), and psychomotor impairment according to neurodevelopmental scales at 24 months after term date.


Condition Intervention Phase
Brain Injuries
Infant, Premature
Device: Cerebral NIRS oximetry
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: SafeBoosC - Safeguarding the Brain of Our Smallest Children - an Investigator-initiated Randomised, Blinded, Multinational, Phase II Feasibility Clinical Trial on Near-infrared Spectroscopy Monitoring Combined With Defined Treatment Guidelines Versus Standard Monitoring and Treatment as Usual in Premature Infants

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • The burden of hypo- and hyperoxia [ Time Frame: 0-72 hours of life ] [ Designated as safety issue: No ]
    The burden of hypo- and hyperoxia in %hours during the first 72 hours after birth, i.e, the area outside the normal ranges of cerebral oxygenation of 55-85% as measured by NIRS.


Secondary Outcome Measures:
  • Brain activities on amplitude-integrated EEG as assessed by the interburst interval. [ Time Frame: at 64 hours of life ] [ Designated as safety issue: No ]
  • Blood and urine biomarkers (brain fatty acid binding protein, neuroketal, and S100β). [ Time Frame: at 6 and 64 hours of life ] [ Designated as safety issue: No ]
  • Brain injury assessed by cerebral ultrasound. [ Time Frame: 1st, 7th, 14th, 35th day of life, and at term date ] [ Designated as safety issue: No ]
  • All-cause mortality [ Time Frame: At term data and 24 months after term date ] [ Designated as safety issue: No ]
  • Serious adverse reactions [ Time Frame: 0 - 7th day of life ] [ Designated as safety issue: Yes ]
    Serious adverse reactions (SAR): any adverse reaction that results in death, is life-threatening, requires prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or requires intervention to prevent permanent impairment or damage.


Estimated Enrollment: 165
Study Start Date: June 2012
Estimated Study Completion Date: December 2015
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cerebral NIRS oximetry + treatment guideline based on reading Device: Cerebral NIRS oximetry
Cerebral NIRS oximetry during the first 72 hours of life.
Other Names:
  • INVOS 5100C with adult SomaSensor (SAFB-SM) (Covidien)
  • NIRO-200NX (Hamamatsy Photonics K.K.)
No Intervention: Blinded cerebral NIRS oximetry

  Eligibility

Ages Eligible for Study:   up to 3 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Neonates born more than 12 weeks preterm (gestational age up to 27 weeks and 6 days).
  • Decision to conduct full life support.
  • Possibility to place cerebral NIRS oximeter within 3 hours after birth.
  • Obtained parental signed written informed consent.

Exclusion Criteria:

  • A clinical decision not to provide full life support.
  • No possibility to place the cerebral NIRS oximeter within 3 hours after birth.
  • Lack of parental signed written informed consent.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01590316

Locations
Denmark
Department of Neonatology, Rigshospitalet
Copenhagen, Denmark, 2100
Sponsors and Collaborators
Gorm Greisen
Investigators
Principal Investigator: Gorm Greisen, MD Rigshospitalet, Capitol Region of Denmark
  More Information

Additional Information:
No publications provided by Rigshospitalet, Denmark

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gorm Greisen, Professor, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT01590316     History of Changes
Other Study ID Numbers: SB010512
Study First Received: May 1, 2012
Last Updated: February 3, 2014
Health Authority: Denmark: National Board of Health
Austria: Austrian Medicines and Medical Devices Agency
Belgium: Federal Agency for Medicinal Products and Health Products
Netherlands: Dutch Health Care Inspectorate
Sweden: The National Board of Health and Welfare
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Italy: National Institute of Health
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Switzerland: Swissmedic
Germany: Federal Institute for Drugs and Medical Devices
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Ireland: Irish Medicines Board

Keywords provided by Rigshospitalet, Denmark:
Brain Injuries
Infant, Premature
Spectroscopy, Near-Infrared
Randomized Controlled Trial

Additional relevant MeSH terms:
Brain Injuries
Brain Diseases
Central Nervous System Diseases
Craniocerebral Trauma
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries

ClinicalTrials.gov processed this record on October 22, 2014