Clinical trial NCT02563717: Comparison Of Respiratory Support After Delivery on Infants Born Before 28 Weeks Gestational Age
Official title: A Randomised Controlled Trial of Delivery Room Intubation Rates Comparing a New System and T-piece Resuscitation System for Initial Stabilisation of Infants Born <28 Weeks
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Respiration; Insufficient or Poor, Newborn
Infant, Premature, Diseases
Keywords: Resuscitation
Positive-Pressure Respiration
Infant, Extremely Premature
Continuous Positive Airway Pressure
Intubation
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
First posted: 2015-09-30
Enrollment: 250
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Trial purpose: For infants born \<28 weeks of age, can initial respiratory resuscitation with new system (low imposed work of breathing and prongs) reduce the frequency of delivery room intubations compared to standard treatment with T-piece resuscitator system (high imposed work of breathing and face mask)?

Trial summary: This is a randomised controlled trial of delivery room intubation rates comparing a new system and T-piece resuscitation system for initial stabilisation of infants born \<28 weeks.

Detailed description: The study is a two arm randomised comparison of two systems (T-piece device and the new system) for respiratory support after delivery of an infant born less than 28 weeks gestational age (GA). This multicentre trial will start at Karolinska University Hospital and other sites can join throughout the study period. The trial is academic with the coordinating investigator as sponsor. No company funding will be considered.

The new device has been designed for neonatal resuscitation and CE-marked for this intended use. The device is operated/handled in a similar way to existing devices and can provide support according to resuscitation guidelines.

During spontaneous breathing the continuous positive airway pressure (CPAP) provided with the new system is more pressure stable and has low imposed work of breathing. The benefits of decreased imposed work of breathing during resuscitation have not previously been investigated. The new system has the option of using prongs as the patient interface. Prongs have shown promising results in trials and have theoretical benefits. We hypothesis that the combined use of prongs and low imposed work of breathing could reduce the number of infants that need mechanical ventilation.

Screening for eligibility and consent will be performed on mothers with threatening delivery of an extremely premature infant (\<28 weeks gestational age). There is no lower gestational age limit but patients should not be included if there is a decision to intubate prior to delivery or treatment limitations.

After a patient has been enrolled the randomisation will be on hold until delivery is imminent. Randomisation will be stratified on centre, gestational age and antenatal steroid treatment. The interventions cannot be blinded.

The management of respiratory support is according to international guidelines and a detailed description is provided in the clinical management appendix. The intervention is respiratory support for the first 10-30 minutes of life and will begin after birth when the infant is transferred to the resuscitation team. The intervention ends 1) when an infant is intubated (primary outcome), 2) after a minimum of 10 minutes support, with the randomized system, the patient is stable and breathing adequately, 3) at 30 minutes when the respiratory support can continue as decided by the clinicians (cross-over not allowed).

Apart from the system used for respiratory support all patients will receive standard care. No assessments or investigations of the trial subjects are planned. Data will be reported by the resuscitation team and collected from records.

The primary outcome is delivery room intubation or death. The secondary outcomes include time to intubation, use of surfactant, use of positive pressure ventilation, respiratory support at 72 hours and temperature on intensive care admission. Safety variables include pneumothorax, intraventricular haemorrhage and problems with ventilation and equipment.

All analysis will be on intention to treat and p\<0.05 considered statistically significant. The primary outcome variable (delivery room intubation or death) will represent a 2x2 cross table and analysed with Pearson chi-square test. The secondary outcomes include Kaplan Meier analysis of time to intubation and comparisons of means for continuous variables. There are no predetermined subgroups. Subgroup analysis will be used to describe the population and to generate hypotheses.

Eligibility criteria: Inclusion Criteria:

1. Born \<28 weeks gestational age at a university hospital
2. Delivery can be vaginal or with caesarean section and steroid prophylaxis to mother can be complete, incomplete or not given

Exclusion Criteria:

1. Decision on treatment limitations before randomisation
2. Decision to intubate infant made before delivery (for example local routine for infants born before 23 weeks GA)
3. Known airway, pulmonary, cardiac, gastro-intestinal tract malformations
4. Known neuromuscular disease
5. No study neonatologist available

Primary outcomes:
measure: Delivery room intubation or death
timeFrame: 0-30 minutes
Secondary outcomes:
measure: Time to primary outcome (intubation or death)
timeFrame: up to 72 hours of age
measure: Death
timeFrame: up to 72 hours of age
measure: Intra ventricular haemorrhage grade III or more
timeFrame: up to 72 hours of age
measure: Airleaks and pneumothorax
timeFrame: up to 72 hours of age
measure: Failed ventilation
timeFrame: 0-30 minutes
measure: Device problems or malfunction
timeFrame: 0-30 minutes
Other outcomes:
measure: Surfactant use in delivery room (DR) and neonatal intensive care unit (NICU)
timeFrame: up to 72 hours of age
measure: The use of positive pressure ventilation (PPV) in delivery room
timeFrame: 0-30 minutes
measure: Use of sustained inflation (not recommended)
timeFrame: 0-30 minutes
measure: Reason for DR intubation
timeFrame: 0-30 minutes
measure: Response to resuscitation measured by APGAR at 1, 5 and 10 minutes
timeFrame: 1-10 minutes
measure: Inspired oxygen level, oxygen saturation (SpO2) and level of CPAP support at 5 and 10 minutes
timeFrame: 5-10 minutes
measure: Patient temperature on NICU admission
timeFrame: 10-180 minutes
measure: Reason for NICU intubation
timeFrame: up to 72 hours of age
measure: Mechanical ventilation at any time <72 h
timeFrame: up to 72 hours of age
measure: Mechanical ventilation or mode of non-invasive support at 72 h
timeFrame: at 72 hours of age
measure: Decisions on treatment limitations during resuscitation
timeFrame: 0-30 minutes
measure: Withdrawal or withholding treatment
timeFrame: up to 72 hours of age
Locations:
city: Reykjavík
country: Iceland
facility: Department of neonatology, University Hospital of Iceland
city: Vilnius
country: Lithuania
facility: Neonatal Unit, Vilnius University Hospital Santaros Klinikos
city: Stavanger
country: Norway
facility: Stavanger University Hospital, Department of Pediatrics
city: Poznan
country: Poland
facility: Department of Neonatology, Poznan University of Medical Sciences
city: Linköping
country: Sweden
facility: University Hospital Linköping, Department of Pediatrics
city: Stockholm
country: Sweden
facility: Karolinska University Hospital, Neonatology department
Study officials:
affiliation: Karolinska Institutet
name: Baldvin Jonsson, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Donaldsson S, Drevhammar T, Li Y, Bartocci M, Rettedal SI, Lundberg F, Odelberg-Johnson P, Szczapa T, Thordarson T, Pilypiene I, Thorkelsson T, Soderstrom L, Chijenas V, Jonsson B; CORSAD Trial Investigators. Comparison of Respiratory Support After Delivery in Infants Born Before 28 Weeks' Gestational Age: The CORSAD Randomized Clinical Trial. JAMA Pediatr. 2021 Sep 1;175(9):911-918. doi: 10.1001/jamapediatrics.2021.1497.