Clinical trial NCT01042600: Randomized Controlled Trial of Surfactant Delivery Via Laryngeal Mask Airway (LMA) Versus Endotracheal Intubation
Official title: Rescue Surfactant for Respiratory Distress Syndrome (RDS) in Newborns: Comparing Efficacy of Delivery Via Laryngeal Mask Airway to Delivery by Endotracheal Intubation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Respiratory Distress Syndrome, Newborn
Keywords: Respiratory distress syndrome
Surfactant
Tracheal intubation
Laryngeal mask airway
Newborn
Lead sponsor: Albany Medical College
Sponsor class: OTHER
Collaborators: name: ONY
name: LMA North America, Inc.
First posted: 2010-01-05
Enrollment: 61
Sex: ALL
Minimum age (years): 4
Maximum age (years): 48
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Rate of Failure of Surfactant Therapy, Either Early (Need for Mechanical Ventilation Within 1 Hour), or Late (FiO2 > 0.60 to Maintain Target SpO2, or Second Dose of Surfactant Within 8 Hours, or Needing More Than 2 Doses of Surfactant).
timeFrame: 96 hours
Secondary outcomes:
measure: Number of Surfactant Doses
timeFrame: 96 hr
measure: Days on Assisted Ventilation
timeFrame: 2 months
measure: Days on Supplemental Oxygen
timeFrame: 2 months
measure: Rate of Pneumothorax
timeFrame: 96 hrs
measure: Rate of BPD (O2 Dependence at the Later of 28 Days of Age or 36 Weeks Postmenstrual Age)
timeFrame: 2 months
measure: Complications During Insertion of LMA
timeFrame: 96 hrs
measure: Mortality Rate
timeFrame: 2 months
Other outcomes:
Locations:
city: Albany
country: United States
facility: Albany Medical Center
state: New York
Study officials:
affiliation: Albany Medical College
name: Joaquim M Pinheiro, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Albany Medical College
name: Querube Santana, MD
role: PRINCIPAL_INVESTIGATOR
References: