Premedication for Less Invasive Surfactant Administration Study (PRELISA)

Study Overview
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Brief Summary
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The purpose of this study is to conduct a double blinded randomized control trial to determine the safety and efficacy of using IV fentanyl and atropine prior to Less Invasive Surfactant Administration (LISA) procedure in preterm infants with Respiratory Distress Syndrome compared to the local standard of care to perform this procedure without any premedication. Hypothesis: In infants greater than or equal to 29 weeks gestational age requiring the Less Invasive Surfactant Administration procedure, premedication with a combination of IV atropine and IV fentanyl will be associated with fewer combined bradycardia events, defined as heartrate less than 100 beats per minute for longer than 10 seconds, and hypoxemia events, defined as saturations less than or equal to 80% for longer than 30 seconds, during the procedure compared with placebo. Specific Aims: To determine if infants receiving IV fentanyl and atropine prior to LISA will have a decrease in hypoxemia and bradycardia events during the procedure compared to infants receiving placebo To determine if infants receiving premedication prior to Less Invasive Surfactant Administration will have higher procedure first attempt success rate compared with infants receiving placebo To determine the effect of premedication on cerebral oxygenation compared to placebo during and for 12 hours after Less Invasive Surfactant Administration using cerebral Near Infrared Spectroscopy To determine the effect of premedication prior to Less Invasive Surfactant Administration on the need for mechanical ventilation for 24 hours after the procedure

Official Title
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Use of Premedication for Less Invasive Surfactant Administration: A Randomized Control Trial

Conditions
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Respiratory Distress Syndrome, Newborn

Intervention / Treatment
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* Drug: IV Atropine and Fentanyl Premedication Arm
* Drug: IV Normal Saline Placebo Arm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants ≥29 weeks gestational age between 0-72 hours of life on CPAP for respiratory support who qualify for the LISA procedure as determined by the primary team using Parkland OPTISURF guidelines Exclusion Criteria: Infants requiring intubation prior to surfactant therapy Infants with known severe congenital anomalies (including complex congenital heart disease, airway, and central nervous system anomalies) Infants born to mothers with known opioid addiction or in a methadone treatment program

Ages Eligible for Study
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Minimum Age: 0 Hours
Maximum Age: 72 Hours

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: IV Atropine and Fentanyl Premedication Arm<br>Participants will receive premedication regimen of 20 micrograms/kilogram intravenous atropine and 0.5 micrograms/kilogram intravenous fentanyl prior to performance of LISA. | Drug: IV Atropine and Fentanyl Premedication Arm<br>* Prior to the LISA procedure, the blinded bedside nurse will infuse IV Atropine, labelled as Atropine/Placebo, over 1 minute, followed by IV fentanyl, labelled as Fentanyl/Placebo, over 20 minutes in the presence of blinded respiratory therapist and primary team provider. After medication infusion, a primary team member will perform Less Invasive Surfactant Administration procedure. Infant vital signs, cerebral Near Infrared Spectroscopy values, pain scores will be monitored and recorded during and for 12 hours after the procedure. Level of respiratory support, oxygen requirement and subsequent need for intubation for 24 hours after the procedure will be obtained from the electronic medical record.<br>* Other names: IV Atropine sulfate and IV Fentanyl citrate;|
| Placebo Comparator: IV Normal Saline Placebo Arm<br>Participants will receive two intravenous Normal Saline infusions in quantities equivalent to the calculated volumes of atropine and fentanyl for participant's weight prior to performance of LISA. | Drug: IV Normal Saline Placebo Arm<br>* Prior to the Less Invasive Surfactant Administration procedure, the blinded bedside nurse will infuse IV Normal Saline, labelled as Atropine/Placebo, over 1 minute, followed by a second infusion of IV Normal Saline, labelled as Fentanyl/Placebo, over 20 minutes in the presence of blinded respiratory therapist and primary team provider. After Normal Saline infusion, primary team member will perform Less Invasive Surfactant Administration procedure. Infant vital signs, cerebral Near Infrared Spectroscopy values, pain scores will be monitored and recorded during and for 12 hours after the procedure. Level of respiratory support, oxygen requirement and subsequent need for intubation for 24 hours after the procedure will be obtained from the electronic medical record.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of bradycardia and hypoxemia events during LISA procedure | Bradycardia events will be defined as heartrate <100 beats per minute for >10 seconds. Heartrate will be obtained from the participant's heartrate monitor. Hypoxemia events will be defined as participant saturation (SpO2) =<80% for >30 seconds. SpO2 will be obtained from the participant's pulse oximeter monitor. Events will be recorded by the respiratory therapist and/ or bedside nurse present during the procedure | Time of medication infusion to completion of LISA procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of time spent with cerebral Near Infrared Spectroscopy (NIRS) values <55% | Cerebral NIRS is a method of noninvasively monitoring cerebral oxygenation. The probes detect a value every 6 seconds and display onto the monitor. Scores between 55-80% are considered within the normal range. Scores less than 55% are considered suboptimal cerebral oxygenation. Percent of time spent with low NIRS values <55% during the 12 hour observation period will be calculated | From time of start of LISA procedure to 12 hours after procedure | 
| Procedure first attempt success rate | Procedure attempt is defined as introduction of laryngoscope blade into the mouth. Procedure success is defined by ability to insert catheter and administer surfactant, without surfactant aspirated from the stomach after administration. Rate will be calculated as a percent of participants in each arm. | At time of LISA procedure | 
| Intubation rate | Rate will be calculated as a percent of participants in each group. Participants need for and timing of intubation will be obtained from electronic medical record. | Within 24 hours after LISA procedure | 
| Mean number of attempts required | Procedure attempt defined as introduction of laryngoscope blade into the mouth | At time of LISA procedure | 
| Mean duration of bradycardia and hypoxemia events | Bradycardia events will be defined as heartrate <100 beats per minute for >10 seconds. Heartrate will be obtained from the participant's heartrate monitor. Hypoxemia events will be defined as participant saturation (SpO2) =<80% for >30 seconds. SpO2 will be obtained from the participant's pulse oximeter monitor. Duration of events in seconds will be recorded by the respiratory therapist and/ or bedside nurse present during the procedure | Time of medication infusion to completion of LISA procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Premedication for Less Invasive Surfactant Administration, Fentanyl and Atropine for Less Invasive Surfactant Administration, Cerebral Near Infrared Spectroscopy monitoring in neonates, Premedication for LISA, Fentanyl and Atropine for LISA, Cerebral NIRS monitoring in neonates