- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02164734
Surfactant Via Endotracheal Tube vs. Laryngeal Mask Airway (LMA) in Preterm Neonates With Respiratory Distress Syndrome
Efficacy of Rescue Surfactant Delivery Via Endotracheal Intubation (INSURE Technique) Versus Laryngeal Mask Airway (LMA) for Respiratory Distress Syndrome (RDS) in Preterm Neonates
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.
Study Overview
Status
Conditions
Intervention / Treatment
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:
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)
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
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Joaquim M Pinheiro, MD, MPH
- Phone Number: 518-262-5421
- Email: pinheij@mail.amc.edu
Study Contact Backup
- Name: Sussan Mbi Ndakor, MD
- Phone Number: 518-262-5421
- Email: mbindas@mail.amc.edu
Study Locations
-
-
New York
-
Albany, New York, United States, 12208
- Albany Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Endotracheal intubation
Endotracheal intubation for surfactant administration, following remifentanil and atropine pre-medication
|
Other Names:
additional premedication in the endotracheal intubation/INSURE arm
|
Experimental: Laryngeal mask airway
Laryngeal mask airway insertion for surfactant administration, following atropine pre-medication
|
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Failing to Avoid Invasive Mechanical Ventilation
Time Frame: 120 hours
|
Failure 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)
|
120 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Surfactant Doses
Time Frame: 120 hours
|
Mean number of surfactant doses per patient
|
120 hours
|
Days on Any Respiratory Support
Time Frame: 3 months
|
Days on any respiratory support (i.e., other than breathing room air)
|
3 months
|
Rate of Pneumothorax
Time Frame: 120 hours
|
proportion of participants with pneumothorax diagnosed radiologically or by transillumination
|
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
|
Defined as oxygen requirement at 36 weeks postmenstrual age if gestational age less than 33 weeks, or beyond 28 days of age if gestational age greater than 32 weeks
|
3 months
|
Number of Participants With Complications During Insertion of LMA or Endotracheal Tube
Time Frame: 120 hours
|
bradycardia, airway obstruction, or cardiopulmonary resuscitation
|
120 hours
|
Mortality Rate
Time Frame: 3 months
|
Mortality prior to hospital discharge (any cause)
|
3 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Early Failure of Surfactant Therapy
Time Frame: 1 hour
|
need of mechanical ventilation within 1 hour of surfactant therapy
|
1 hour
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Joaquim M Pinheiro, MD, MPH, Albany Medical College
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Respiratory Tract Diseases
- Respiration Disorders
- Lung Diseases
- Disease
- Infant, Newborn, Diseases
- Infant, Premature, Diseases
- Syndrome
- Respiratory Distress Syndrome
- Respiratory Distress Syndrome, Newborn
- Physiological Effects of Drugs
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Analgesics, Opioid
- Narcotics
- Remifentanil
Other Study ID Numbers
- 3768
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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