Premedication for Less Invasive Surfactant Administration Study (PRELISA)

Sponsor

University of Texas Southwestern Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05065424

Collaborator

Chiesi Farmaceutici S.p.A. (Industry)

Enrollment

Location

Arms

13.6

Anticipated Duration (Months)

4.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Respiratory Distress Syndrome, Newborn	Drug: IV Atropine and Fentanyl Premedication Arm Drug: IV Normal Saline Placebo Arm	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

58 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 14, 2022

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

May 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IV Atropine and Fentanyl Premedication Arm 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 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. Other Names: IV Atropine sulfate and IV Fentanyl citrate
Placebo Comparator: IV Normal Saline Placebo Arm 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 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.

Arm

Intervention/Treatment

Experimental: IV Atropine and Fentanyl Premedication Arm

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

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.

Other Names:

IV Atropine sulfate and IV Fentanyl citrate

Placebo Comparator: IV Normal Saline Placebo Arm

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

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.

Outcome Measures

Primary Outcome Measures

Number of bradycardia and hypoxemia events during LISA procedure [Time of medication infusion to completion of 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

Secondary Outcome Measures

Percent of time spent with cerebral Near Infrared Spectroscopy (NIRS) values <55% [From time of start of LISA procedure to 12 hours after procedure]
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
Procedure first attempt success rate [At time of LISA procedure]
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.
Intubation rate [Within 24 hours after LISA procedure]
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.
Mean number of attempts required [At time of LISA procedure]
Procedure attempt defined as introduction of laryngoscope blade into the mouth
Mean duration of bradycardia and hypoxemia events [Time of medication infusion to completion of 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. Duration of events in seconds will be recorded by the respiratory therapist and/ or bedside nurse present during the procedure

Eligibility Criteria

Criteria

Ages Eligible for Study:

0 Hours to 72 Hours

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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