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

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ClinicalTrials.gov Identifier: NCT02164734
Recruitment Status : Recruiting
First Posted : June 17, 2014
Last Update Posted : January 14, 2019
Sponsor:
Collaborators:
University of Rochester
ONY
Information provided by (Responsible Party):
Joaquim M.B. Pinheiro, Albany Medical College

Tracking Information
First Submitted Date  ICMJE June 13, 2014
First Posted Date  ICMJE June 17, 2014
Last Update Posted Date January 14, 2019
Study Start Date  ICMJE June 2014
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 13, 2014)
Avoidance of invasive mechanical ventilation [ Time Frame: 120 hours ]
Rate of success of success of surfactant therapy in avoiding invasive mechanical ventilation or clinically equivalent outcomes (FiO2 > 0.60 to maintain target SpO2, second dose of surfactant within 8 hours, or more than 2 total doses of surfactant)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 3, 2015)
  • Number of surfactant doses [ Time Frame: 120 hours ]
  • Days on any respiratory support [ Time Frame: 3 months ]
  • Rate of Pneumothorax [ Time Frame: 120 hours ]
  • Rate of bronchopulmonary dysplasia (O2 dependence at the later of 28 days of age or 36 weeks postmenstrual age) [ Time Frame: 3 months ]
  • Complications during insertion of LMA or endotracheal tube [ Time Frame: 120 hours ]
  • Mortality rate [ Time Frame: 3 months ]
    Mortality prior to hospital discharge
Original Secondary Outcome Measures  ICMJE
 (submitted: June 13, 2014)
  • Number of surfactant doses [ Time Frame: 120 ]
  • Days on any respiratory support [ Time Frame: 3 months ]
  • Rate of Pneumothorax [ Time Frame: 120 hours ]
  • Rate of bronchopulmonary dysplasia (O2 dependence at the later of 28 days of age or 36 weeks postmenstrual age) [ Time Frame: 3 months ]
  • Complications during insertion of LMA or endotracheal tube [ Time Frame: 120 hours ]
  • Mortality rate [ Time Frame: 3 months ]
    Mortality prior to hospital discharge
Current Other Pre-specified Outcome Measures
 (submitted: June 13, 2014)
Early failure of surfactant therapy [ Time Frame: 1 hour ]
need of mechanical ventilation within 1 hour of surfactant therapy
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Surfactant Via Endotracheal Tube vs. Laryngeal Mask Airway (LMA) in Preterm Neonates With Respiratory Distress Syndrome
Official Title  ICMJE Efficacy of Rescue Surfactant Delivery Via Endotracheal Intubation (INSURE Technique) Versus Laryngeal Mask Airway (LMA) for Respiratory Distress Syndrome (RDS) in Preterm Neonates
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Respiratory Distress Syndrome, Newborn
Intervention  ICMJE
  • Device: Endotracheal intubation
    Other Name: INSURE
  • Device: Laryngeal mask airway
    Other Name: LMA North America
  • Drug: remifentanil
    additional premedication in the endotracheal intubation/INSURE arm
Study Arms  ICMJE
  • Active Comparator: Endotracheal intubation
    Endotracheal intubation for surfactant administration, following remifentanil and atropine pre-medication
    Interventions:
    • Device: Endotracheal intubation
    • Drug: remifentanil
  • Experimental: Laryngeal mask airway
    Laryngeal mask airway insertion for surfactant administration, following atropine pre-medication
    Intervention: Device: Laryngeal mask airway
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 13, 2014)
130
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 48 Hours   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Joaquim M Pinheiro, MD, MPH 518-262-5421 pinheij@mail.amc.edu
Contact: Sussan Mbi Ndakor, MD 518-262-5421 mbindas@mail.amc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02164734
Other Study ID Numbers  ICMJE 3768
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Joaquim M.B. Pinheiro, Albany Medical College
Study Sponsor  ICMJE Albany Medical College
Collaborators  ICMJE
  • University of Rochester
  • ONY
Investigators  ICMJE
Principal Investigator: Joaquim M Pinheiro, MD, MPH Albany Medical College
PRS Account Albany Medical College
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP