Comparison Of Respiratory Support After Delivery on Infants Born Before 28 Weeks Gestational Age

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Respiration; Insufficient or Poor, Newborn, Infant, Premature, Diseases

Intervention / Treatment
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* Device: T-piece used for respiratory support (several manufacturers)
* Device: New system used for respiratory support


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Born <28 weeks gestational age at a university hospital Delivery can be vaginal or with caesarean section and steroid prophylaxis to mother can be complete, incomplete or not given Exclusion Criteria: Decision on treatment limitations before randomisation Decision to intubate infant made before delivery (for example local routine for infants born before 23 weeks GA) Known airway, pulmonary, cardiac, gastro-intestinal tract malformations Known neuromuscular disease No study neonatologist available
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Reference Device: T-piece System<br> | Device: T-piece used for respiratory support (several manufacturers)<br>* Infants will receive support by a standard T-piece resuscitator system (manufacturer not dictated in protocol). Apart from the system used for respiratory support all patients will receive standard care (specified in management protocol)<br>* Other names: Other T-piece manufacturers;|
| Active Comparator: Investigational Device: The New System<br> | Device: New system used for respiratory support<br>* Infants will receive support by the new system (manufactured by Inspiration Healthcare, UK). Apart from the system used for respiratory support all patients will receive standard care (specified in management protocol)<br>* Other names: Manufacturing and CE-marking by Inspiration Healthcare, UK;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delivery room intubation or death | The primary outcome is delivery room intubation or death. Death has to be included in the primary outcome since patients that die may not always be intubated. The variable is a dichotomous outcome and reported by the resuscitation team. | 0-30 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to primary outcome (intubation or death) | The time (minutes:hours) that a patient reach primary outcome. Data reported by resuscitation team or collected at patient record review of the first three days of life. This is a safety endpoint. | up to 72 hours of age | 
| Death | The time (minutes:hours) that a patient died. Data reported by resuscitation team or collected at patient record review of the first three days of life. This is a safety endpoint. | up to 72 hours of age | 
| Intra ventricular haemorrhage grade III or more | The number of patients with an intra ventricular hemorrhage grade III or more. Data collected at patient record review of the first three days of life. This is a safety endpoint. | up to 72 hours of age | 
| Airleaks and pneumothorax | The number of patients with airleaks or pneumothorax during resuscitation or the first 72 hours of life. Data reported by resuscitation team or collected at patient record review of the first three days of life. This is a safety endpoint. | up to 72 hours of age | 
| Failed ventilation | The number of patients with failed ventilation during resuscitation. Data reported by resuscitation team. This is a safety endpoint. | 0-30 minutes | 
| Device problems or malfunction | The instances that there was a problem with the randomized intervention. Data reported by resuscitation team. This is a safety endpoint. Device problems or malfunction activates the adverse events handling protocol. | 0-30 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Resuscitation, Positive-Pressure Respiration, Infant, Extremely Premature, Continuous Positive Airway Pressure, Intubation