Surfactant Via Endotracheal Tube vs. Laryngeal Mask Airway (LMA) in Preterm Neonates With Respiratory Distress Syndrome

NCT ID: NCT02164734

Last Updated: 2023-09-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 93 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2020-12-31

Brief Summary

In this study, newborn babies with respiratory distress syndrome (RDS), receiving oxygen via nasal continuous airway pressure (CPAP) modalities, and needing surfactant treatment will be randomized to standard delivery of surfactant via and endotracheal tube airway (inserted after pre-medication for pain with a short-acting narcotic), or to surfactant delivery via laryngeal mask airway (LMA). The intent is to remove the airways and return babies to non-invasive CPAP support, after surfactant is given. The primary outcome measure is the rate of failure of initial surfactant therapy. Standardized failure criteria are reached: a) early, if the baby is unable to be placed back on non-invasive CPAP (i.e., needs tracheal intubation and mechanical ventilation) or, b) late, if the baby requires ventilation, retreatment with surfactant within 8 hours or more than 2 doses of surfactant.

The objective of this protocol is to reduce the need for endotracheal intubation and mechanical ventilation in preterm neonates with RDS needing rescue surfactant therapy by instilling surfactant though an LMA, while achieving comparable efficacy of surfactant treatment.

The hypothesis is that surfactant treatment through an LMA will decrease the proportion of babies with RDS who require mechanical ventilation or subsequent intubation, when compared to standard surfactant treatment following endotracheal intubation with sedation.

Detailed Description

Respiratory Distress Syndrome (RDS) due to deficiency of pulmonary surfactant is common in preterm newborns. Early treatment with surfactant improves oxygenation, reduces the need for subsequent mechanical ventilation, decreases the incidence of pulmonary air leaks and chronic lung disease and it also reduces mortality in extremely premature newborns. Optimal treatment of RDS includes surfactant therapy and avoidance of invasive mechanical ventilation by using nasal continuous positive airway pressure modes (NCPAP or NIPPV). The current standard method of surfactant delivery requires tracheal intubation and at least brief positive-pressure ventilation, as in the INSURE (Intubation-Surfactant-Extubation) approach. Because tracheal intubation causes pain and vagal-mediated physiologic instability in neonates, premedication with atropine and a narcotic is recommended. However, narcotic premedication increases respiratory depression, which may require sustained mechanical ventilation, thus contributing to the failure of INSURE. In a recent trial at our center, standard pretreatment with morphine and atropine was associated with failure of INSURE in more than 2/3 of patients. Consequently, we have recently changed our standard premedication for INSURE to the combination of atropine and remifentanil (a rapid onset, short-acting narcotic). The Laryngeal Mask Airway (LMA) is a commercially available, less invasive artificial airway that does not need to be inserted into the trachea; it is FDA-approved for use in neonates; preliminary data suggest that it can be used for surfactant administration, which in our trial was associated with a lower failure rate than the morphine plus INSURE approach.

The main objective of this study protocol is reduce the need for endotracheal intubation and mechanical ventilation in preterm neonates with mild to moderate RDS needing rescue surfactant therapy by instilling surfactant though an LMA. A second objective is to compare the efficacy of surfactant administered via LMA versus endotracheal tube (ETT) in decreasing the severity of RDS. Additionally, we will further evaluate the safety of surfactant administration via LMA.

The primary hypothesis is that surfactant therapy delivered via LMA is not inferior to surfactant therapy delivered via transient intubation (INSURE technique) with short-acting narcotic premedication for mild to moderate RDS in preterm neonates.

This randomized controlled trial will include babies with mild-to-moderate RDS, less than 48 hours of age, with gestational age 27 0/7 to 36 6/7 weeks, treated with NCPAP (or other NIPPV modality) ≥ 5 cm H2O and FiO2 between 0.30 and 0.60 for at least 2 hours to maintain oxygen saturation by pulse oximetry (SpO2) 90-95%.

After informed consent is obtained, babies are randomly assigned (from sealed, opaque, consecutively numbered envelopes), to "ETT" or "LMA" groups. The "ETT" group is managed according to our current INSURE approach to surfactant therapy (endotracheal intubation following premedication with atropine + remifentanil), whereas the "LMA" group will be pre-medicated with atropine before LMA insertion for surfactant administration.

Both groups will receive Infasurf (3mL/kg) instilled in 2 aliquots via their respective airway, followed by PPV for at least 5 minutes. The artificial airway will be removed and the patient returned to NCPAP/NIPPV by 15 minutes, if spontaneous respirations are adequate. Indications for surfactant re-dosing and mechanical ventilation will be equivalent for both groups. Babies will continue or initiate assisted ventilation via ETT if any of the following occurs:

• Persistent apnea;
• Severe retractions;
• Inability to wean FiO2 < 60%

Criteria for re-dosing with surfactant:

1. Within 8 hours after first dose of surfactant:

• FiO2 20% higher than the baseline FiO2, after excluding other obvious causes of respiratory insufficiency such as pneumothorax.

If early re-dosing of surfactant is needed in patients of either group, it will be administered via ETT (i.e., LMA patients will be intubated, and will receive the dose of surfactant via ETT)

2. Beyond 8 hours of the first dose of surfactant:

• FiO2 is ≥ 60%, or;
• FiO2 is ≥ 30% associated with worsening clinical signs of RDS.

If late re-dosing is needed in patients of the LMA group, use of the LMA is permitted for the second dose. In the ETT group, all doses are given via the ETT.

Conditions

Respiratory Distress Syndrome, Newborn

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Endotracheal intubation

Endotracheal intubation for surfactant administration, following remifentanil and atropine pre-medication

Group Type: ACTIVE_COMPARATOR

Endotracheal intubation

Intervention Type: DEVICE

remifentanil

Intervention Type: DRUG

additional premedication in the endotracheal intubation/INSURE arm

Laryngeal mask airway

Laryngeal mask airway insertion for surfactant administration, following atropine pre-medication

Group Type: EXPERIMENTAL

Laryngeal mask airway

Intervention Type: DEVICE

Interventions

Endotracheal intubation

Intervention Type: DEVICE

Laryngeal mask airway

Intervention Type: DEVICE

remifentanil

additional premedication in the endotracheal intubation/INSURE arm

Intervention Type: DRUG

Other Intervention Names

INSURE; LMA North America

Eligibility Criteria

Inclusion Criteria

• Mild-to-moderate RDS;
• Postnatal age 2 to 48 hours;
• Gestational age 27 0/7 to 36 6/7 weeks;
• Treated with nasal CPAP modalities ≥ 5 cm H2O and FiO2 between 0.30 and 0.60 for at least 2 hours to maintain SpO2 90-95%;
• Informed consent

Exclusion Criteria

• Weight < 800 g;
• Airway anomalies;
• Pulmonary air leaks;
• Craniofacial or cardiothoracic malformations

• Minimum Eligible Age: 2 Hours
• Maximum Eligible Age: 48 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Rochester

OTHER

Sponsor Role: collaborator

ONY

INDUSTRY

Sponsor Role: collaborator

Albany Medical College

OTHER

Sponsor Role: lead

Responsible Party

Joaquim M.B. Pinheiro

Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joaquim M Pinheiro, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Albany Medical College

Locations

Albany Medical Center

Albany, New York, United States

Countries

United States

References

Gallup JA, Ndakor SM, Pezzano C, Pinheiro JMB. Randomized Trial of Surfactant Therapy via Laryngeal Mask Airway Versus Brief Tracheal Intubation in Neonates Born Preterm. J Pediatr. 2023 Mar;254:17-24.e2. doi: 10.1016/j.jpeds.2022.10.009. Epub 2022 Oct 12.

Reference Type: DERIVED

PMID: 36241051 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

3768

Identifier Type: -

Identifier Source: org_study_id