Oxygen Toxicity in the Resuscitation in Extremely Premature Infants

Premature Birth Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00494702
• Other study ID #: PIO51O5
• Secondary ID: FISPI05105
• Status: Completed
• Phase: Phase 3
• First received: June 28, 2007
• Last updated: October 14, 2008
• Start date: April 2005
• Est. completion date: September 2008

Study information

• Verified date: October 2008
• Source: Fundacion Para La Investigacion Hospital La Fe
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ministry of Health and Consumption
• Study type: Interventional

Clinical Trial Summary

The investigators hypothesize that using low oxygen concentrations during resuscitation of extremely premature infants will avoid oxidative stress derived damage and improve outcome.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: September 2008
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 3 Minutes

Eligibility

Inclusion Criteria:

• Prematurity of less than 28 weeks gestation

Exclusion Criteria:

• Severe malformations

• Chromosomopathies

• Informed consent not signed

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asphyxia
• Asphyxia Neonatorum
• Birth Asphyxia
• Premature Birth

Intervention

Procedure:
• Resuscitation
Use of inspiratory fraction of oxygen needed to achieve oxygen saturation in the preset limits 85-88%
• Resuscitation
Oxygen inspiratory fraction needed to keep oxygen saturation in the preset limits of 90-93%

Locations

Country	Name	City	State
Spain	Servicio de Neonatologia	Valencia

Sponsors (2)

Lead Sponsor	Collaborator
Fundacion Para La Investigacion Hospital La Fe	Instituto de Salud Carlos III

Country where clinical trial is conducted

Spain, 

References & Publications (8)

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. — View 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. — View Citation

Saugstad OD, Ramji S, Vento M. Oxygen for newborn resuscitation: how much is enough? Pediatrics. 2006 Aug;118(2):789-92. — View 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. Epub 2004 Sep 20. Review. — View Citation

Vento M, Asensi M, Sastre J, García-Sala F, Pallardó FV, Viña J. Resuscitation with room air instead of 100% oxygen prevents oxidative stress in moderately asphyxiated term neonates. Pediatrics. 2001 Apr;107(4):642-7. — View Citation

Vento M, Asensi M, Sastre J, Lloret A, García-Sala F, Miñana JB, Viña 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. — View Citation

Vento M, Asensi M, Sastre J, Lloret A, García-Sala F, Viña J. Oxidative stress in asphyxiated term infants resuscitated with 100% oxygen. J Pediatr. 2003 Mar;142(3):240-6. Erratum in: J Pediatr. 2003 Jun;142(6):616. — View Citation

Vento M, Sastre J, Asensi MA, Viña 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. Epub 2005 Sep 1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Achievement of a targeted saturation of 85% at 15 min of life.		30 min	Yes
Secondary	Neonatal mortality		28 days of life	No
Secondary	Oxidative stress		at day 1, 2 and 7	No
Secondary	Bronchopulmonary dysplasia		36 weeks postconceptional age	No
Secondary	Retinopathy of prematurity		40 weeks postconceptional	No
Secondary	Neurodevelopment		24 months postnatal	No