Oxygen Toxicity in the Resuscitation in Extremely Premature Infants (OXTOX)
Primary Purpose
Birth Asphyxia, Premature Birth
Status
Completed
Phase
Phase 3
Locations
Spain
Study Type
Interventional
Intervention
Resuscitation
Resuscitation
Sponsored by
About this trial
This is an interventional treatment trial for Birth Asphyxia focused on measuring Asphyxia, Resuscitation, Oxidative stress, Prematurity, Follow up
Eligibility Criteria
Inclusion Criteria:
- Prematurity of less than 28 weeks gestation
Exclusion Criteria:
- Severe malformations
- Chromosomopathies
- Informed consent not signed
Sites / Locations
- Servicio de Neonatologia
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
LOX
HOX
Arm Description
Low saturation group of premature infants that will be kept within preset limits of 85-89%
HOX group of premature infants will be kept within preset saturation limits of 90-93%
Outcomes
Primary Outcome Measures
Achievement of a targeted saturation of 85% at 15 min of life.
Secondary Outcome Measures
Neonatal mortality
Oxidative stress
Bronchopulmonary dysplasia
Retinopathy of prematurity
Neurodevelopment
Full Information
NCT ID
NCT00494702
First Posted
June 28, 2007
Last Updated
October 14, 2008
Sponsor
Fundacion Para La Investigacion Hospital La Fe
Collaborators
Instituto de Salud Carlos III
1. Study Identification
Unique Protocol Identification Number
NCT00494702
Brief Title
Oxygen Toxicity in the Resuscitation in Extremely Premature Infants
Acronym
OXTOX
Official Title
Achievement of a Targeted Saturation in Extremely Low Gestational Age Neonates Resuscitated With Low or High Oxygen Concentration: A Prospective Randomized Trial
Study Type
Interventional
2. Study Status
Record Verification Date
October 2008
Overall Recruitment Status
Completed
Study Start Date
April 2005 (undefined)
Primary Completion Date
March 2008 (Actual)
Study Completion Date
September 2008 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Fundacion Para La Investigacion Hospital La Fe
Collaborators
Instituto de Salud Carlos III
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The investigators hypothesize that using low oxygen concentrations during resuscitation of extremely premature infants will avoid oxidative stress derived damage and improve outcome.
Detailed Description
This is a prospective randomized trial enrolling premature infants of less than 28 weeks gestation. Patients are randomly assigned to become resuscitation with an initial oxygen inspiratory fraction (FiO2) of 30% or 90%. Main objective is to reach a target saturation of 85% at 15 min of life.
Immediately after birth pre-and-postductal pulse oximeters are set and oxygen saturation (SpO2) continuously monitored and registered as long as the patient requires oxygen supplementation. FiO2 is stepwise adjusted (increased or decreased 10%) every 90 sec according to heart rate, SpO2 and responsiveness.
Blood samples are drawn from umbilical cord and at day 1, 2 and 7 from peripheral vein to determine oxidative stress markers (GSH, GSSG), angiogenic factors (VEGF, VEGF receptors, Angiopoietin), pro-inflammatory markers (IL8, TNF alfa) and pro-apoptotic markers (Fas Ligand; Cytochrome C).
Urine is collected every day during the first week of life to determine oxidative stress markers (8-oxo-dG; O-tyrosine; F2 isoprostanes; Isofurans).
Babies are followed in the NICU and clinical condition recorded. Serial examinations for ROP and Auditory evoked potentials will be performed. Neurodevelopmental outcome is evaluated at 2 years of postnatal life. Main outcome: Achievement of a target saturation of 85% at 15 min of life. Secondary outcomes: acute complications during delivery; chronic complications (BPD, ROP, IPVH); mortality in the neonatal period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Birth Asphyxia, Premature Birth
Keywords
Asphyxia, Resuscitation, Oxidative stress, Prematurity, Follow up
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
88 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LOX
Arm Type
Experimental
Arm Description
Low saturation group of premature infants that will be kept within preset limits of 85-89%
Arm Title
HOX
Arm Type
Active Comparator
Arm Description
HOX group of premature infants will be kept within preset saturation limits of 90-93%
Intervention Type
Procedure
Intervention Name(s)
Resuscitation
Intervention Description
Use of inspiratory fraction of oxygen needed to achieve oxygen saturation in the preset limits 85-88%
Intervention Type
Procedure
Intervention Name(s)
Resuscitation
Intervention Description
Oxygen inspiratory fraction needed to keep oxygen saturation in the preset limits of 90-93%
Primary Outcome Measure Information:
Title
Achievement of a targeted saturation of 85% at 15 min of life.
Time Frame
30 min
Secondary Outcome Measure Information:
Title
Neonatal mortality
Time Frame
28 days of life
Title
Oxidative stress
Time Frame
at day 1, 2 and 7
Title
Bronchopulmonary dysplasia
Time Frame
36 weeks postconceptional age
Title
Retinopathy of prematurity
Time Frame
40 weeks postconceptional
Title
Neurodevelopment
Time Frame
24 months postnatal
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Minute
Maximum Age & Unit of Time
3 Minutes
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Prematurity of less than 28 weeks gestation
Exclusion Criteria:
Severe malformations
Chromosomopathies
Informed consent not signed
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maximo Vento, Phd, Md
Organizational Affiliation
Hospital Universitario La Fe
Official's Role
Principal Investigator
Facility Information:
Facility Name
Servicio de Neonatologia
City
Valencia
ZIP/Postal Code
46009
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
11335737
Citation
Vento M, Asensi M, Sastre J, Garcia-Sala F, Pallardo FV, Vina J. Resuscitation with room air instead of 100% oxygen prevents oxidative stress in moderately asphyxiated term neonates. Pediatrics. 2001 Apr;107(4):642-7. doi: 10.1542/peds.107.4.642.
Results Reference
background
PubMed Identifier
12537311
Citation
Vento M, Asensi M, Sastre J, Lloret A, Garcia-Sala F, Minana JB, Vina J. Hyperoxemia caused by resuscitation with pure oxygen may alter intracellular redox status by increasing oxidized glutathione in asphyxiated newly born infants. Semin Perinatol. 2002 Dec;26(6):406-10. doi: 10.1053/sper.2002.37312.
Results Reference
background
PubMed Identifier
12640369
Citation
Vento M, Asensi M, Sastre J, Lloret A, Garcia-Sala F, Vina J. Oxidative stress in asphyxiated term infants resuscitated with 100% oxygen. J Pediatr. 2003 Mar;142(3):240-6. doi: 10.1067/mpd.2003.91. Erratum In: J Pediatr. 2003 Jun;142(6):616.
Results Reference
background
PubMed Identifier
12897277
Citation
Saugstad OD, Ramji S, Irani SF, El-Meneza S, Hernandez EA, Vento M, Talvik T, Solberg R, Rootwelt T, Aalen OO. Resuscitation of newborn infants with 21% or 100% oxygen: follow-up at 18 to 24 months. Pediatrics. 2003 Aug;112(2):296-300. doi: 10.1542/peds.112.2.296.
Results Reference
background
PubMed Identifier
15452400
Citation
Saugstad OD, Ramji S, Vento M. Resuscitation of depressed newborn infants with ambient air or pure oxygen: a meta-analysis. Biol Neonate. 2005;87(1):27-34. doi: 10.1159/000080950. Epub 2004 Sep 20.
Results Reference
background
PubMed Identifier
16141440
Citation
Vento M, Sastre J, Asensi MA, Vina J. Room-air resuscitation causes less damage to heart and kidney than 100% oxygen. Am J Respir Crit Care Med. 2005 Dec 1;172(11):1393-8. doi: 10.1164/rccm.200412-1740OC. Epub 2005 Sep 1.
Results Reference
background
PubMed Identifier
16882835
Citation
Saugstad OD, Ramji S, Vento M. Oxygen for newborn resuscitation: how much is enough? Pediatrics. 2006 Aug;118(2):789-92. doi: 10.1542/peds.2006-0832. No abstract available.
Results Reference
background
PubMed Identifier
17426659
Citation
Bookatz GB, Mayer CA, Wilson CG, Vento M, Gelfand SL, Haxhiu MA, Martin RJ. Effect of supplemental oxygen on reinitiation of breathing after neonatal resuscitation in rat pups. Pediatr Res. 2007 Jun;61(6):698-702. doi: 10.1203/pdr.0b013e3180534171.
Results Reference
background
PubMed Identifier
18450889
Citation
Escrig R, Arruza L, Izquierdo I, Villar G, Saenz P, Gimeno A, Moro M, Vento M. Achievement of targeted saturation values in extremely low gestational age neonates resuscitated with low or high oxygen concentrations: a prospective, randomized trial. Pediatrics. 2008 May;121(5):875-81. doi: 10.1542/peds.2007-1984.
Results Reference
derived
Learn more about this trial
Oxygen Toxicity in the Resuscitation in Extremely Premature Infants
We'll reach out to this number within 24 hrs