Premedication Trial for Tracheal Intubation of the NEOnate

Study Overview
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Brief Summary
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Multicenter double blind randomized controlled trial comparing atropine+propofol vs atropine+atracurium+sufentanil as a premedication prior to endotracheal intubation of the neonate. Primary outcome: pulse oxymetry value < 80% for more than 60 seconds. Secondary outcomes: number of attempts, duration of the procedure, changes in physiologic parameters, short- and long-term neurodevelopmental outcome. Hypothesis: atropine + propofol compared to atropine+atracurium+sufentanil will significantly reduce the frequency of severe hypoxemia.

Official Title
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Double Blind Randomized Controlled Trial Comparing Atropine+Propofol Versus Atropine+Atracurium+Sufentanil as a Premedication Prior to Semi-urgent or Elective Endotracheal Intubation of Term and Preterm Newborns

Conditions
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Premedication, Endotracheal Intubation

Intervention / Treatment
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* Drug: atropine+ propofol
* Drug: atropine + atracurium + sufentanil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Corrected age < 45 weeks of gestational age Currently hospitalized in a neonatal intensive care unit Requiring semi-urgent or elective intubation Equipped with a reliable and permeable IV line Parental consent Exclusion Criteria: Lack of parental consent Parental refusal Sedative or anesthetic treatment in the previous 24 hours Hemodynamic compromise defined as mean blood pressure< corrected GA and/or refill time > 3 seconds Upper airway malformation Life-threatening situation requiring immediate intubation Inclusion in another trial not permitting any other participation Impossibility to establish venous access Any contra-indication to any experimental drug

Ages Eligible for Study
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Maximum Age: 28 Days

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atropine + Propofol<br> | Drug: atropine+ propofol<br>* Atropine bolus: 20 µg/kg Propofol injected over 60 seconds: 1 mg/kg for infants < 1000g - Renewable once 2.5 mg/kg for infants > 1000G - Possible additional dose of 1 mg/kg<br>|
| Active Comparator: Atropine + atracurium + sufentanil<br> | Drug: atropine + atracurium + sufentanil<br>* Atropine bolus: 20 µg/kg Atracurium: 0.3 mg/kg- Possible additional dose of 0.1 mg/kg Sufentanil: 0.1 µg/kg for infants < 1000g 0.2 µg/kg for infants > 1000g<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Prolonged Desaturation | Pulse oxymetry value measured by Masimo technology below 80% for 60 seconds or more. Duration of intubation is defined by the time between first laryngoscope insertion and last laryngoscope removal after successful intubation. Successful intubation is defined by clear bilateral breath sounds, increasing heart rate and saturation (if previously low) and appropriate flow curves on the ventilator. | During intubation procedure, expected duration 1 to 15 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Intubation Attempts |  | During intubation procedure, expected duration 1 to 15 minutes | 
| Duration of Intubation Procedure | Although the initial definition of procedure duration in the registered protocol was the time between the first laryngoscope insertion and last laryngoscope removal after successful intubation, the variable collected in the clinical research form was defined as the time between first laryngoscope insertion and the fixation of the tube with tape. | Expected duration 1 to 15 minutes | 
| Heart Rate | Heart rate recordings 1 minute before the first injection and at 3, 6, 9, 12, 15, 30, 45 and 60 minutes after the first injection | from 1 minute before to 60 minutes after the start of premedication | 
| Short Term Neurological Outcome: Worsening of Head Ultrasound | Worsening of head ultrasound scans in the 7 days after intubation from the preinclusion evaluation, defined as either a normal scan before inclusion and any grade intraventricular hemorrhage (IVH) afterwards, or as a preinclusion grade 1 or 2 IVH scan deteriorating to grade 3 or 4 IVH, according to Papile's classification; This analysis was not centralized but performed in each center according to its usual protocols. | Within 7 days after inclusion | 
| Number of Patients Surviving Without Ages and Stages Questionnaire Score Below Threshold at Age 2 | Survival without risk of neurodevelopmental delay. Risk of neurodevelopmental delay was defined as no Ages and Stages Questionnaires (ASQ) domain score below threshold (-2 SD) at 2 years of corrected age. The ASQ includes 30 items in 5 neurodevelopmental domains: communication abilities, gross motor skills, fine motor skills, problem solving abilities, and personal-social skills. For each domain, the score obtained by the sum of the items ranges from 0 to 60 and the overall maximum ASQ score is 300 points. For each domain, the score can be categorized using established screening thresholds: an ASQ score <-2 SD below the mean suggests a risk of neurodevelopmental delay in that domai. | At 2 years corrected age | 
| Pulse Oxymetry | Pulse oxymetry recordings 1 minute before the first injection and at 3, 6, 9, 12, 15, 30, 45 and 60 minutes after the first injection | from 1 minute before to 60 minutes after the start of premedication | 
| Mean Blood Pressure | Blood pressure recordings 1 minute before the first injection and at 3, 6, 9, 12, 15, 30, 45 and 60 minutes after the first injection | from 1 minute before to 60 minutes after the start of premedication | 
| Transcutaneous PCO2 (TcPCO2) Measurement | TcPCO2 recordings 1 minute before the first injection and at 3, 6, 9, 12, 15, 30, 45 and 60 minutes after the first injection | from 1 minute before to 60 minutes after the start of premedication | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Newborn, Anaesthesia, opioids, propofol, neuromuscular blocker, atropine