|- candidate number||28311|
|- NTR Number||NTR6878|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||6-dec-2017|
|- Secondary IDs||P17.209 METC van het LUMC / NL62897.058.17 toetsingonline |
|- Public Title||Improving respiration with oxygen evaluation|
|- Scientific Title||High versus low initial oxygen to improve the breathing effort of preterm infants at birth|
|- hypothesis||Although most preterm infants breathe at birth, their respiratory drive is weak and often insufficient to aerate their lungs and establish gas exchange. Extra oxygen is often needed to correct hypoxia, but could then lead to hyperoxia. The optimal concentration of oxygen to start stabilisation after birth is still not clear, as both hypoxia and hyperoxia can attribute to organ injury. To reduce the risk of hyperoxia, currently an initial low oxygen concentration is recommended during stabilisation, accepting the risk of a period of hypoxia. However, hypoxia inhibits respiratory drive in preterm infants. Starting with a higher level of oxygen could lead to a shorter duration of hypoxia and thus stimulate breathing effort of preterm infants, but increase the risk for hyperoxia. Improving the respiratory drive decreases the need for additional ventilation or intubation and mechanical ventilation.|
|- Healt Condition(s) or Problem(s) studied||Preterm infants, Resuscitation, Oxygen|
|- Inclusion criteria||Preterm infants of 24-30 weeks of gestation will be randomized to start stabilisation after birth with a FiO2 of either 1.0 or 0.3, after which FiO2 will be titrated based on oxygen saturation. |
|- Exclusion criteria||Congenital abnormality or condition that might have an adverse effect on breathing or ventilation, if these conditions are not already diagnosed before birth, including: congenital diaphragmatic hernia, trachea-oesophageal fistula or cyanotic heart disease. |
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||28-jan-2018|
|- planned closingdate||1-okt-2018|
|- Target number of participants||50|
|- Interventions||Based on randomization, stabilisation after birth will be initiated with a FiO2 of either 1.0 or 0.3, after which FiO2 will be titrated based on oxygen saturation. SpO2 will be measured continuously and aimed to maintain within target ranges described by Dawson et al. (2010).(22) |
In both groups, other interventions needed for stabilisation and thereafter will be given conform standard care.
|- Primary outcome||The main study parameter is respiratory effort, expressed as:
- Average respiratory minute volume in the first 5 minutes after birth
|- Secondary outcome||Secondary study parameters are;|
- Interaction of respiratory minute volume in the first 5 minutes after birth with time
- Average tidal volumes in the first 5 minutes after birth
- Interaction of tidal volumes in the first 5 minutes after birth with time
- Average rate of rise to maximum tidal volumes in the first 5 minutes after birth
- Interaction of rate of rise to maximum tidal volumes in the first 5 minutes after birth with time
- Percentage of recruitment breaths with tidal volumes above 8 ml/kg in the first 5 minutes after birth
- Concentration of 8-iso-prostaglandin F2á(25), an oxidative stress metabolite associated with hyperoxia in blood. This blood sample will be taken together with the sample for measuring standard blood analyses, so that the infant will not be exposed to an extra venepuncture or capillary puncture.
|- Timepoints||The first 5 minutes after birth|
|- Trial web site|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES|| Janneke Dekker|
|- CONTACT for SCIENTIFIC QUERIES|| Janneke Dekker|
|- Sponsor/Initiator ||Leiden University Medical Center (LUMC)|
(Source(s) of Monetary or Material Support)
|- Brief summary||Objective The objective of this study is to compare the direct effect of the administration of an initial FiO2 of 1.0 versus 0.3 on respiratory effort during stabilisation of preterm infants in the first 5 minutes after birth. After evaluation of the initial settings, FiO2 will be titrated based on the oxygen saturation target range.|
Study design A singlecenter randomized controlled trial.
Study population Preterm infants of 24-30 weeks of gestation will be randomized.
Intervention Based on randomization, stabilisation after birth will be started with a FiO2 of either 1.0 or 0.3, after which FiO2 will be titrated based on the oxygen saturation target range. In both groups, other interventions needed for stabilisation and thereafter will be given conform standard care.
Main study parameters/endpoints The main study parameter is respiratory effort in the first 5 minutes after birth expressed as average respiratory minute volume.
Secondary parameters are inspired tidal volumes, rate of rise to maximum tidal volumes, percentage of recruitment breaths with tidal volumes above 8 ml/kg and duration of hypoxia and hyperoxia during stabilisation and plasma levels of markers of oxidative stress (8-iso-prostaglandin F2á).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness
Most preterm infants breathe insufficiently at birth and develop respiratory distress syndrome. Previous studies demonstrated that achieving adequate oxygenation directly after birth is difficult and additional oxygen supplementation is required in most cases. The only difference between groups in the proposed study is the initial FiO2 during stabilisation after birth. After the initial setting, FiO2 will be titrated up in the low FiO2-group and titrated down in the high FiO2-group following target ranges for oxygen saturation.
In preterm infants at birth both hypoxia and hyperoxia needs to be avoided as they are both associated to increased risk for organ injury. Currently the starting FiO2 is low (0.3), increasing the risk for hypoxia in the first minutes, insufficient respiratory drive and an increased risk for additional ventilation or intubation and mechanical ventilation. When starting with a high FiO2 (1.0), the risk for hypoxia will decrease, but could increase the risk for hyperoxia. However, in both groups, the goal is to obtain normoxia in the newborn as soon as possible after birth. To minimize risks for hypoxia and hyperoxia in both groups FiO2 will be titrated based on oxygen saturations guided by target ranges defined in this protocol.
|- Main changes (audit trail)|
|- RECORD||6-dec-2017 - 2-feb-2018|