Randomized Controlled Trial of Surfactant Delivery Via Laryngeal Mask Airway (LMA) Versus Endotracheal Intubation

NCT ID: NCT01042600

Last Updated: 2019-07-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2012-11-30

Brief Summary

In this study, newborn babies with respiratory distress syndrome (RDS), receiving oxygen via nasal CPAP, and needing surfactant treatment will be randomized to standard delivery of surfactant via and endotracheal tube airway(inserted after pre-medication for pain), or to surfactant delivery via laryngeal mask airway (LMA). The intent is to remove the airways and return babies to nasal CPAP, 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 CPAP (needs mechanical ventilation) or, b) late, if the baby requires 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 with standard surfactant treatment following sedation and endotracheal intubation.

Detailed Description

Respiratory Distress Syndrome (RDS) due to deficiency of lung 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 (NCPAP). The current standard method of surfactant delivery requires tracheal intubation and at least brief positive-pressure ventilation. Tracheal intubation causes pain and leads to vagal-mediated physiologic instability in neonates; therefore, premedication with morphine and atropine is routinely practiced in our setting. However, premedication with morphine often increases respiratory depression, requiring sustained mechanical ventilation. 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, and preliminary data suggest that it can be used for surfactant administration.

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 evaluate the safety of surfactant administration via LMA.

The primary hypothesis is that surfactant treatment via the LMA approach will decrease the proportion of babies with RDS who require mechanical ventilation or subsequent intubation, when compared with standard surfactant as administered to the ETT group.

This randomized controlled trial will include babies with mild-to-moderate RDS, between 4 to 48 hours of age, with gestational age 29 0/7 to 36 6/7 weeks, treated with NCPAP ≥ 5 cm H2O and FiO2 between 0.30 and 0.60 for at least 2 hours to maintain SpO2 88-95%, and informed consent. Exclusion criteria are weight < 1000 g, airway anomalies, pulmonary air leaks, and craniofacial and cardiothoracic malformations.

After informed consent is obtained, babies are randomly assigned (from sealed, opaque, consecutively numbered envelopes), to the "ETT" or "LMA". The "ETT" group is managed according to our current practice of surfactant therapy (endotracheal intubation following premedication with atropine + morphine), 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 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 (early re-dosing):

• 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, the dose 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 (late re-dosing):

• FiO2 is ≥ 60%, or;
• FiO2is ≥ 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.

Primary Outcome Measures:

Rate of failure of early surfactant rescue therapy in the 2 groups, using the following criteria to differentiate early from late failure:

• Criteria for early failure (within 1 hour):

1. The need of mechanical ventilation within 1 hour of surfactant therapy.

2. Use of Narcan to avoid mechanical ventilation after surfactant therapy.

• Criteria for late failure (beyond 1 hour):

1. Sustained FiO2 > 0.60 to maintain target SpO2

2. Second dose of surfactant within 8 hours after the first dose.

3. More than 2 doses of surfactant.

Babies will have FiO2 adjusted to maintain SpO2 88-95%, per current practice. Other aspects of weaning ventilatory support will be managed by clinicians' preference.

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 tube insertion for surfactant administration, following morphine and atropine pre-medication

Group Type: ACTIVE_COMPARATOR

Endotracheal tube insertion

Intervention Type: DEVICE

Endotracheal tube insertion after premedication with atropine (0.02 mg/kg) and morphine (0.1 mg/kg)

Laryngeal mask airway

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

Group Type: EXPERIMENTAL

Laryngeal mask airway insertion

Intervention Type: DEVICE

Laryngeal mask airway insertion after premedication with atropine (0.02 mg/kg)

Interventions

Endotracheal tube insertion

Endotracheal tube insertion after premedication with atropine (0.02 mg/kg) and morphine (0.1 mg/kg)

Intervention Type: DEVICE

Laryngeal mask airway insertion

Laryngeal mask airway insertion after premedication with atropine (0.02 mg/kg)

Intervention Type: DEVICE

Other Intervention Names

LMA North America

Eligibility Criteria

Inclusion Criteria

• Mild-to-moderate RDS
• Postnatal age 4 to 48 hours
• Gestational age 29 0/7 to 36 6/7 weeks
• Treated with nasal CPAP ≥ 5 cm H2O and FiO2 between 0.30 and 0.60 for at least 2 hours to maintain SpO2 88-95%
• Informed consent

Exclusion Criteria

• Weight < 1000 g
• Airway anomalies
• Pulmonary air leaks
• Craniofacial or cardiothoracic malformations

• Minimum Eligible Age: 4 Hours
• Maximum Eligible Age: 48 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ONY

INDUSTRY

Sponsor Role: collaborator

LMA North America, Inc.

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

Querube Santana, MD

Role: PRINCIPAL_INVESTIGATOR

Albany Medical College

Locations

Albany Medical Center

Albany, New York, United States

Countries

United States

Other Identifiers

2599

Identifier Type: -

Identifier Source: org_study_id