Respiratory Distress Syndrome in Premature InfantNEOSURFNCT07098910
Surfactant Therapy Via Supraglottic Airway to Preterm Neonates With RDS in Vietnam
A study testing Surfactant Administration Through Laryngeal or Supraglottic Airways (SALSA) and Intubation - Surfactant administration - Extubation (INSURE) in people with Respiratory Distress Syndrome in Premature Infant, run by Karolinska Institutet at 1 site in Vietnam.
Trial summary
Preterm babies often have trouble breathing because their lungs are not fully developed. This condition is called respiratory distress syndrome (RDS). A medicine called surfactant helps their lungs open up and work better. Read more about this study
- Who is it for?
- Ages Up to 48 hours
- Conditions the study is for
- Respiratory Distress Syndrome in Premature Infant
- What is being tested?
- Surfactant Administration Through Laryngeal or Supraglottic Airways (SALSA) and Intubation - Surfactant administration - Extubation (INSURE)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 440 participants
- Where
- 1 siteVietnam
- Study dates
- 28 Sep 2025to 30 Mar 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 48 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Inborn neonate (=born in the hospital), AND
- Gestational age <34+0 weeks, AND
- Birth weight ≥750g, AND
- Age <48 hours, AND
- Diagnosis of RDS, confirmed with a chest x-ray or lung ultrasound, except in cases where immediate treatment is necessary and imaging would cause a delay AND
- Indication for surfactant treatment: Infant on non-invasive support (CPAP/NIPPV) and FiO2 >0.30 to maintain oxygen saturation (SpO2) between 90% and 95%
Who cannot join
- Severe respiratory insufficiency in need of intubation at delivery room
- Severe respiratory insufficiency in need of intubation and invasive mechanical ventilation after arrival to NICU
- Previous surfactant administration
- Previous invasive mechanical ventilation
- Known pneumothorax
- Major malformations
Show all 9Show fewer
- Physician not confident with study intervention
- The physician decided not to include the patient due to a preference for performing INSURE
- Excluded due to time constraints preventing completion of informed consent and trial procedures
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Vietnam1 site, 1 recruiting
- Recruiting
Phu San Hanoi Hospital - Hanoi Obstetrics and Gynecology Hospital
Hanoi, 118000
Hien Vu, M.D., +84 904 999 455, hien.vu@ki.se
Hung Trong Mai, M.D.
About this study
Official title: Surfactant Therapy Via Supraglottic Airway Device Versus Endotracheal Intubation to Prevent Mechanical Ventilation in Preterm Neonates With Respiratory Distress Syndrome: An Open-label, Non-inferiority, Randomized Controlled Trial at a Level-III Neonatal Intensive Care Unit in Vietnam
Preterm babies often have trouble breathing because their lungs are not fully developed. This condition is called respiratory distress syndrome (RDS). A medicine called surfactant helps their lungs open up and work better. It is usually given through a procedure called INSURE, where a breathing tube is placed into the baby's trachea (via an endotracheal tube) to deliver the medicine. While effective, this method is invasive and can be uncomfortable and risky for the baby.
A newer, less invasive method called SALSA uses a soft mask placed in the throat (a laryngeal mask airway) instead of an endotracheal tube to give the surfactant. This randomized controlled trial will compare SALSA to the traditional INSURE method to see if it works just as well in preventing the need for invasive breathing support within three days of treatment.
The study will include preterm babies born before 34 weeks of pregnancy and weighing at least 750 grams, at Phu San Hanoi Hospital in Vietnam. If SALSA is found to be safe and effective, it may offer a gentler, less invasive, and easier-to-perform option for treating respiratory distress syndrome in premature babies.
Read the detailed description
BACKGROUND
Respiratory distress syndrome (RDS) remains a leading cause of morbidity and mortality among preterm infants worldwide. Surfactant replacement therapy has significantly improved outcomes; however, standard techniques such as INSURE (Intubation-Surfactant-Extubation), while effective in avoiding mechanical ventilation, require endotracheal intubation-a procedure associated with potential complications and demanding considerable clinical expertise. Less invasive methods, such as surfactant administration via a laryngeal mask airway (SALSA), have shown promising results in reducing the need for mechanical ventilation in moderately preterm infants in smaller studies. This approach may be particularly beneficial in low- and middle-income countries (LMICs), where high birth volumes and limited availability of skilled personnel and advanced respiratory support highlight the need for simpler, safer interventions.
Evidence for SALSA in more immature preterm populations and from large randomized controlled trials remains limited. One key barrier to broader adoption has been the lack of appropriately sized supraglottic airway devices for very small infants. A recent feasibility study by this research team, using newly available preterm-sized devices, demonstrated that SALSA is feasible for surfactant delivery in infants weighing between 750 and 1500 grams (NCT06606444). A randomized controlled trial is now warranted to assess the effectiveness and safety of SALSA, particularly in lower-middle-income settings and among extremely low birth weight infants.
AIM AND HYPOTHESIS
This trial primarily aims to evaluate whether surfactant administration via the SALSA method is non-inferior to the current standard INSURE method in preventing IMV in preterm neonates with RDS admitted to a tertiary-level neonatal unit in South-Easia. It also seeks to compare the two methods in terms of safety, ease of use, infant comfort during the procedure, and morbidity during hospital admission.
We hypothesize that in preterm neonates with RDS, born before gestational week 34 and with a birth weight of at least 750 grams (P), surfactant administration via SALSA (I) will be non-inferior to INSURE (C) in preventing invasive mechanical ventilation (IMV) (O) within 72 hours after the procedure (T).
TRIAL DESIGN
This is an investigator-initiated, single-centre, two-arm parallel-group, open-label, non-inferiority RCT with a 1:1 allocation ratio per neonate. The trial entails an internal pilot-phase of the first 100 patients.
PARTICIPANTS:
See Eligibility section.
STUDY SITE
Phu San Hanoi Hospital (PSH) is the largest obstetric hospital in Hanoi, Vietnam, with about 40 000 deliveries every year and about 10% preterm births. The neonatal department is divided into three units: a level III NICU (35 beds), a high dependency unit (60 beds), and a Kangaroo mother care (KMC) unit (45 beds) which are staffed by 73 nurses and 21 doctors. Head ultrasound is made within 7 days of life and before discharge for all preterm infants <32 weeks of gestation as routine care, with additional assessments in between as needed. Echocardiography to screen for persistent ductus arteriosus is performed in neonates with clinical signs and treated medically (ibuprofen or paracetamol) if found haemodynamically significant. All infants <32 weeks of gestation are routinely examined for retinopathy of prematurity by ophthalmologist.
STUDY PROCEDURE
All infants requiring surfactant therapy will be screened for eligibility by the NICU team on a continuous basis. Caregivers will be approached for informed consent prior to inclusion. Eligible infants with consent will be randomized immediately before surfactant administration using a computer-generated, block-randomized sequence to receive either SALSA (intervention) or INSURE (control). The interventions are described in detail under "Arms and Interventions." For SALSA, a CE-marked, supraglottic airway device, Neo i-gel®, available in three sizes 0.85, 0.75, and 0.65 (Intersurgical Ltd), will be used. Procedural data will be collected through direct observation by the clinical team, while background characteristics and follow-up variables will be extracted from medical records by the study team. All data will be entered into an electronic case report form (eCRF) in REDCap. A subset of 50 patients per treatment arm will be video-recorded and reviewed for detailed analysis of procedure duration, physiologic stability and pain.
OUTCOMES
The primary outcome is: Failure of surfactant therapy to prevent invasive mechanical ventilation within 72 hours after first surfactant administration.
Decision to initiate mechanical ventilation via intubation will be made at the discretion of the treating physician, guided by the local NICU criteria for mechanical ventilation.
Secondary outcomes are listed under Outcome Measures.
SAMPLE SIZE
According to a baseline study conducted in 2023 (unpublished data), we assume that 21,5% of neonates in the control group (INSURE) would meet failure criteria. If there is no difference between SALSA and INSURE in terms of use of IMV (21,5% in both arms), 418 neonates need to be enrolled to be 80% sure that the upper limit of a one-sided 95% confidence interval will exclude an absolute difference larger than 10% in favour of INSURE. The sample is increased to 440 neonates to take into account a dropout of 5%.
PILOT PHASE
The trial will begin with an internal pilot phase designed to assess the feasibility of recruitment, adherence to trial procedures, data completeness, and intervention fidelity. Efficacy will not be evaluated. The internal pilot phase will enrol 100 neonates (approximately 23% of the total sample size), with recruitment anticipated over 12 months. This design will allow feedback on recruitment capacity and process quality and enabling adaptations.
The pilot phase will assess outcomes related to recruitment feasibility, adherence to intervention, adherence to mechanical ventilation criteria, retention, data completeness, data integrity and acceptability. Pilot outcomes are listed under Outcome Measures.
An interim assessment will be performed after the enrolment of 50 participants or after 12 months, whichever comes first. Only pilot outcomes will be assessed. The final analysis of the pilot phase will take place upon completion of enrolment of 100 participants. Following this evaluation, the Trial Steering Committee will determine whether to continue the study without modifications, implement protocol amendments-such as the inclusion of additional trial sites or adjustments to trial procedures-or temporarily suspend the trial to allow for a redesign. These decisions will be guided by a balanced assessment across all pilot domains.
- Being tested
- Surfactant Administration Through Laryngeal or Supraglottic Airways (SALSA), Intubation - Surfactant administration - Extubation (INSURE)
- Keywords
- surfactant therapy, supraglottic airway device, laryngeal mask airway, preterm infant, neonate, newborn, vietnam, SALSA, RDS, respiratory distress syndrome, very low birth weight
- Medical subject headings
- Premature Birth, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Surfactant Administration Through Laryngeal or Supraglottic Airways (SALSA)Procedure or surgery
Also called Laryngeal mask airway surfactant administration, Surfactant Therapy via Laryngeal Mask Airway, Laryngeal Mask Airway for Surfactant Administration in Neonates, Supraglottic airway devices for surfactant treatment
While the infant is spontaneously breathing on nasal CPAP, the NICU physician will place the supraglottic airway device (SAD) and assess airway adequacy via CO₂ detection, chest movement, bilateral breath sounds, gastric insufflation, oxygen saturation, and heart rate. Each placement attempt should last no more than 30 seconds, with up to two attempts allowed. Surfactant (Curosurf 200 mg/kg) will be given slowly in 1-2 ml aliquots via a CE-marked preterm-sized SAD, Neo i-gel® (sizes 0.85, 0.75, 0.65; Intersurgical Ltd). The infant should primarily breathe spontaneously with PEEP from a T-piece resuscitator and receive gentle PPV if needed. PPV is continued for 30 seconds after surfactant administration before SAD removal. A reservoir bag may be used secondarily to provide PPV. If surfactant delivery via SALSA fails, the INSURE method (Intubation-Surfactant-Extubation) will be attempted.
Intubation - Surfactant administration - Extubation (INSURE)Procedure or surgery
Study participants will receive surfactant therapy administered via brief endotracheal intubation - surfactant administration - and extubation (INSURE). Infants will be ventilated using a T-piece resuscitator with PEEP of 6 cm H20 and positive pressure ventilation (20 cm H20) for a couple of minutes (no more than 15 minutes) with adjustable FiO2. No mechanical ventilation will be used. Secondarily a reservoir-bag will be used for ventilation.
| Study group | Role | What they receive |
|---|---|---|
| Surfactant therapy administered via supraglottic airway device (SALSA) | Experimental | Study participants will receive surfactant therapy via a preterm size supraglottic airway device (SALSA). Receives: Procedure: Surfactant Administration Through Laryngeal or Supraglottic Airways (SALSA) |
| Endotracheal intubation - surfactant administration - and extubation (INSURE) | Active comparator | Study participants will receive surfactant therapy administered via brief endotracheal intubation - surfactant administration - and extubation (INSURE). Receives: Procedure: Intubation - Surfactant administration - Extubation (INSURE) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Failure of surfactant therapy to prevent invasive mechanical ventilation
Categorical variable (Yes/No). Failure in terms of the need for endotracheal intubation and invasive mechanical ventilation. Decision to initiate mechanical ventilation via intubation will be made at the discretion of the treating physician, guided by the local NICU criteria for mechanical ventilation. Data is extracted from medical records.
Analysis considerations:
- If an infant deteriorates after randomization and requires intubation with mechanical ventilation before the allocated intervention can be performed, the case will be classified as failure in the intention-to-treat (ITT) analysis, but excluded from the per-protocol (PP) analysis.
- If an infant improves after randomization and the allocated intervention is not required, the case will be included and not considered a failure in the ITT analysis, but excluded from the PP analysis.
Measured: Within 72 hours after first surfactant administration
Secondary outcomes (36)
Early failure of surfactant therapy
Categorical variable (Yes/No). Defined as use of invasive mechanical ventilation within 1 hour of first surfactant administration. Data is collected from medical record.
Measured: Within 1 hour after first surfactant administration
Late failure of surfactant therapy
Categorical variable (Yes/No). Defined as use of invasive mechanical ventilation. Data is collected from medical record.
Measured: Between 1 hour and 72 hours after first surfactant administration
Time to initiation of invasive mechanical ventilation after the procedure
Numerical variable. Elapsed time between procedure initiation and mechanical ventilation, derived from medical record timestamps.
Measured: Before discharge (about 6-15 weeks)
Invasive mechanical ventilation at any time during admission
Categorical variable (Yes/No). Decision to initiate mechanical ventilation via intubation will be made at the discretion of the treating physician, guided by the local NICU criteria for mechanical ventilation. Data is extracted from medical records.
Measured: Before discharge (about 6-15 weeks)
Incidence of severe bradycardia
Defined as <60 beats per minute. Measured by pulse oximetry and noted by team performing procedure.
Measured: During the procedure, an average of 5-10 minutes
Incidence of severe desaturation
Defined as SpO2 <70%. Measured by pulse oximetry and noted by team performing procedure.
Measured: During the procedure, an average of 5-10 minutes
Change in FiO₂ (%) from before the procedure to 3 hours after surfactant administration
Numerical variable. Observed by clinical team and noted in CRF.
Measured: Within 10 minutes before the procedure to 3 hours after first surfactant administration
Number of placement attempts needed to place LMA or ETT
Numerical variable. Placement attempt defined as LMA or ETT entering the mouth with intent to place device in the airway. Observed by clinical team during procedure and noted in CRF.
Measured: During the procedure, an average of 5-10 minutes
Failure to place supraglottic airway device (SAD) or endotracheal tube (ETT) at first attempt
Categorical variable (Yes/No). Failure to place device (SAD or ETT) and obtain an adequate airway on first attempt, as assessed by treating physician.
Measured: During the procedure, an average of 5-10 minutes
Volume of postintervention surfactant-resembling gastric residuals
Numerical variable (ml). Gastric residuals are aspirated before procedure and directly after procedure (after SAD or ETT is removed) and volume of fluid content resembling surfactant is observed by clinical team and noted in CRF.
Measured: Directly after first surfactant administration
Proportion (%) of postintervention gastric surfactant aspirated of total surfactant dose
Numerical variable (%). Fraction (calculated from residual aspirated surfactant and total dose (mL). Observed by clinical team during procedure and noted in CRF.
Measured: Directly after first surfactant administration
Postintervention gastric surfactant aspirated greater than 10% of surfactant dose
Categorical variable (Yes/No). Calculated from ratio below 10% from Proportion (%) of postintervention gastric surfactant aspirated. Observed by clinical team during procedure and noted in CRF.
Measured: Directly after first surfactant administration
Reflux of surfactant during procedure
Categorical variable (Yes/No). Clinical reflux of surfactant during procedure. Observed by clinical team during procedure and noted in CRF.
Measured: Directly after first surfactant administration
Number of surfactant doses given during admission
Numerical variable. Number of surfactant doses. Data is collected from medical record.
Measured: Before discharge (about 6-15 weeks)
Administration of a second surfactant dose within 6 hours of the first dose
Categorical variable (Yes/No). Data is collected from medical record.
Measured: 6 hours after initial dose
Method of subsequent surfactant doses
Method used for delivery of subsequent surfactant doses. Data is collected from medical record.
Measured: Before discharge (about 6-15 weeks)
Incidence of mortality within 7 days after birth
Categorical variable (Yes/No). Data is collected from medical record.
Measured: Seven days of age
Incidence of mortality prior to discharge
Categorical variable (Yes/No). Data is collected from medical record.
Measured: Before discharge (about 6-15 weeks)
Time to death
Numerical variable. Elapsed time between birth and death. Derived from medical record notations.
Measured: Before discharge (about 6-15 weeks)
Duration of invasive mechanical ventilation
Numerical variable (days). Data is collected from medical record.
Measured: Before discharge (about 6-15 weeks)
Duration of Continuous Positive Airway Pressure (CPAP) or Non-invasive Positive Pressure Ventilation (NIPPV)
Numerical variable (days). Data is collected from medical record.
Measured: Before discharge (about 6-15 weeks)
Duration of any respiratory support (IMV, CPAP, NIPPV or oxygen by nasal cannula)
Numerical variable (days). Data is collected from medical record.
Measured: Before discharge (about 6-15 weeks)
Duration of hospital admission
Numerical variable (days). Data is collected from medical record.
Measured: Before discharge (about 6-15 weeks)
Incidence of bronchopulmonary dysplasia
Categorical variable (Yes/No). Defined as need for oxygen or ventilatory support for at least 28 days and persisting at 36 weeks of postmenstrual age (ventilatory support: IMV, CPAP/NIPPV or O2 by nasal cannula). Data is collected from medical record.
Measured: 36 weeks post menstrual age
Postnatal steroid treatment before discharge
Categorical variable (Yes/No). Data is collected from medical record.
Measured: Before discharge (about 6-15 weeks)
Incidence of IVH grade III or IV
Categorical variable (Yes/No). Head ultrasound is made within 7 days of life and before discharge for all preterm infants <32 weeks of gestation (and older infants with complications) as routine care, with additional assessments in between as needed. Data is collected from medical record.
Measured: Before discharge (about 6-15 weeks)
Incidence of cystic periventricular leukomalacia
Categorical variable (Yes/No). Head ultrasound is made within 7 days of life and before discharge for all preterm infants <32 weeks of gestation (and older infants with complications) as routine care, with additional assessments in between as needed. Data is collected from medical record.
Measured: Before discharge (about 6-15 weeks)
Incidence of pneumothorax, requiring drainage
Categorical variable (Yes/No). Pneumothorax requiring drainage by needle thoracocentesis or chest drain. Data is collected from medical record.
Measured: Before discharge (about 6-15 weeks)
Incidence of pulmonary haemorrhage, requiring circulatory support
Categorical variable (Yes/No). Defined as pulmonary haemorrhage requiring circulatory support like fluid bolus, blood transfusion or vasopressors/inotropes. Data collected from medical records.
Measured: Before discharge (about 6-15 weeks)
Incidence of persistent ductus arteriosus requiring treatment
Categorical variable (Yes/No). Requiring medical (ibuprofen or paracetamol) or surgical treatment. Data is collected from medical record.
Measured: Before discharge (about 6-15 weeks)
Incidence of early-onset sepsis
Defined by clinical signs, laboratory findings, or positive blood culture, as assessed by the treating clinician within 72 hours of birth. Data is collected from medical record.
Measured: Within 72 hours after birth.
Incidence of late-onset sepsis
Categorical variable (Yes/No). Defined by clinical signs, laboratory findings, or positive blood culture, as assessed by the treating clinician from 72 hours after birth to discharge. Data is collected from medical record.
Measured: >72 hours after birth to discharge (about 6-15 weeks)
Incidence of retinopathy of prematurity, ≥ grade 3
Categorical variable (Yes/No). All infants <32 weeks of gestation are assessed by Ophthalmologists as clinical routine. Data is collected from medical record.
Measured: Before discharge (about 6-15 weeks)
Incidence of transfer due to need of intestinal surgery
Categorical variable (Yes/No). Eg. need of surgery due to necrotizing enterocolitis, spontaneous intestinal perforation or ileus. All cases with indication for surgery are referred to the neighbouring Vietnam National Children's Hospital. Data is collected from medical record.
Measured: Before discharge (about 6-15 weeks)
Incidence of transfer to higher-level care
Categorical variable (Yes/No). Any indication. Data is collected from medical record.
Measured: Before discharge (about 6-15 weeks)
Incidence of major morbidity before discharge
Categorical variable (Yes/No). Composite outcome defined as any of the following morbidities: intraventricular haemorrhage grade III or IV, cystic periventricular leukomalacia, retinopathy of prematurity ≥ grade 3, or BPD at 36 weeks' postmenstrual age
Measured: Before discharge (about 6-15 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2025
- Study start28 Sep 2025
- Primary completion31 Dec 2028 (estimated)
- Study completion30 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Respiratory Distress Syndrome in Premature InfantStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Investigator-initiated, single-centre, two-arm parallel-group, open-label, non-inferiority RCT with a 1:1 allocation ratio per neonate. The trial entails an internal pilot-phase of the first 100 patients.
- Masking
- None (open label)
- Enrolment
- 440 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- Göteborg University, University of Padova, Hanoi Obstetrics and Gynecology Hospital
- Responsible party
- Principal investigator, Tobias Alfvén, Karolinska Institutet
- Investigators
- Tobias Alfvén, Professor, M.D, Ph.D, Principal investigator, Department of Global Public Health, Karolinska Institutet, Solna, Sweden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07098910
- Sponsor's protocol ID
- 2089 CN/PS
- Other IDs
- Project-ID 2018-02770 VR, RS2020-0, ALFGBG-998065, 2-4435/2024
- Acronym
- NEOSURF
- Status last verified
- May 2026
- First submitted
- 21 Jul 2025
- Last updated
- 27 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The datasets used and/or analysed during the current study will be available from the principal investigator on reasonable request after publication of results.
Publications
Zapata HA, Fort P, Roberts KD, Kaluarachchi DC, Guthrie SO. Surfactant Administration Through Laryngeal or Supraglottic Airways (SALSA): A Viable Method for Low-Income and Middle-Income Countries. Front Pediatr. 2022 Mar 16;10:853831. doi: 10.3389/fped.2022.853831. eCollection 2022.
PubMed 35372140Dempsey T, Brismar TB, Svensson-Marcial A, Blennow M, Alfven T, Hook SM, Pejovic N. Radiologic evaluation of three smaller-sized supraglottic airway device prototypes for low-birth-weight neonates. Br J Anaesth. 2025 Nov;135(5):1551-1553. doi: 10.1016/j.bja.2025.05.038. Epub 2025 Jul 3. No abstract available.
PubMed 40610284Abdel-Latif ME, Walker E, Osborn DA. Laryngeal mask airway surfactant administration for prevention of morbidity and mortality in preterm infants with or at risk of respiratory distress syndrome. Cochrane Database Syst Rev. 2024 Jan 25;1(1):CD008309. doi: 10.1002/14651858.CD008309.pub3.
PubMed 38270182
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Surfactant Therapy Via Supraglottic Airway Device Versus Endotracheal Intubation to Prevent Mechanical Ventilation in Preterm Neonates With Respiratory Distress Syndrome: An Open-label, Non-inferiority, Randomized Controlled Trial at a Level-III Neonatal Intensive Care Unit in Vietnam
- ClinicalTrials.gov ID
- NCT07098910
- Acronym / sponsor ID
- NEOSURF / 2089 CN/PS
- Keywords
- surfactant therapy, supraglottic airway device, laryngeal mask airway, preterm infant, neonate, newborn, vietnam, SALSA
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 440 participants (estimated)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- Göteborg University, University of Padova, Hanoi Obstetrics and Gynecology Hospital
- Study start
- 28 Sep 2025 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 30 Mar 2029 (estimated)
- First posted
- 1 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Preterm babies often have trouble breathing because their lungs are not fully developed. This condition is called respiratory distress syndrome (RDS). A medicine called surfactant helps their lungs open up and work better. It is usually given through a procedure called INSURE, where a breathing tube is placed into the baby's trachea (via an endotracheal tube) to deliver the medicine. While effective, this method is invasive and can be uncomfortable and risky for the baby.
A newer, less invasive method called SALSA uses a soft mask placed in the throat (a laryngeal mask airway) instead of an endotracheal tube to give the surfactant. This randomized controlled trial will compare SALSA to the traditional INSURE method to see if it works just as well in preventing the need for invasive breathing support within three days of treatment.
The study will include preterm babies born before 34 weeks of pregnancy and weighing at least 750 grams, at Phu San Hanoi Hospital in Vietnam. If SALSA is found to be safe and effective, it may offer a gentler, less invasive, and easier-to-perform option for treating respiratory distress syndrome in premature babies.
Detailed description
BACKGROUND
Respiratory distress syndrome (RDS) remains a leading cause of morbidity and mortality among preterm infants worldwide. Surfactant replacement therapy has significantly improved outcomes; however, standard techniques such as INSURE (Intubation-Surfactant-Extubation), while effective in avoiding mechanical ventilation, require endotracheal intubation-a procedure associated with potential complications and demanding considerable clinical expertise. Less invasive methods, such as surfactant administration via a laryngeal mask airway (SALSA), have shown promising results in reducing the need for mechanical ventilation in moderately preterm infants in smaller studies. This approach may be particularly beneficial in low- and middle-income countries (LMICs), where high birth volumes and limited availability of skilled personnel and advanced respiratory support highlight the need for simpler, safer interventions.
Evidence for SALSA in more immature preterm populations and from large randomized controlled trials remains limited. One key barrier to broader adoption has been the lack of appropriately sized supraglottic airway devices for very small infants. A recent feasibility study by this research team, using newly available preterm-sized devices, demonstrated that SALSA is feasible for surfactant delivery in infants weighing between 750 and 1500 grams (NCT06606444). A randomized controlled trial is now warranted to assess the effectiveness and safety of SALSA, particularly in lower-middle-income settings and among extremely low birth weight infants.
AIM AND HYPOTHESIS
This trial primarily aims to evaluate whether surfactant administration via the SALSA method is non-inferior to the current standard INSURE method in preventing IMV in preterm neonates with RDS admitted to a tertiary-level neonatal unit in South-Easia. It also seeks to compare the two methods in terms of safety, ease of use, infant comfort during the procedure, and morbidity during hospital admission.
We hypothesize that in preterm neonates with RDS, born before gestational week 34 and with a birth weight of at least 750 grams (P), surfactant administration via SALSA (I) will be non-inferior to INSURE (C) in preventing invasive mechanical ventilation (IMV) (O) within 72 hours after the procedure (T).
TRIAL DESIGN
This is an investigator-initiated, single-centre, two-arm parallel-group, open-label, non-inferiority RCT with a 1:1 allocation ratio per neonate. The trial entails an internal pilot-phase of the first 100 patients.
PARTICIPANTS:
See Eligibility section.
STUDY SITE
Phu San Hanoi Hospital (PSH) is the largest obstetric hospital in Hanoi, Vietnam, with about 40 000 deliveries every year and about 10% preterm births. The neonatal department is divided into three units: a level III NICU (35 beds), a high dependency unit (60 beds), and a Kangaroo mother care (KMC) unit (45 beds) which are staffed by 73 nurses and 21 doctors. Head ultrasound is made within 7 days of life and before discharge for all preterm infants <32 weeks of gestation as routine care, with additional assessments in between as needed. Echocardiography to screen for persistent ductus arteriosus is performed in neonates with clinical signs and treated medically (ibuprofen or paracetamol) if found haemodynamically significant. All infants <32 weeks of gestation are routinely examined for retinopathy of prematurity by ophthalmologist.
STUDY PROCEDURE
All infants requiring surfactant therapy will be screened for eligibility by the NICU team on a continuous basis. Caregivers will be approached for informed consent prior to inclusion. Eligible infants with consent will be randomized immediately before surfactant administration using a computer-generated, block-randomized sequence to receive either SALSA (intervention) or INSURE (control). The interventions are described in detail under "Arms and Interventions." For SALSA, a CE-marked, supraglottic airway device, Neo i-gel®, available in three sizes 0.85, 0.75, and 0.65 (Intersurgical Ltd), will be used. Procedural data will be collected through direct observation by the clinical team, while background characteristics and follow-up variables will be extracted from medical records by the study team. All data will be entered into an electronic case report form (eCRF) in REDCap. A subset of 50 patients per treatment arm will be video-recorded and reviewed for detailed analysis of procedure duration, physiologic stability and pain.
OUTCOMES
The primary outcome is: Failure of surfactant therapy to prevent invasive mechanical ventilation within 72 hours after first surfactant administration.
Decision to initiate mechanical ventilation via intubation will be made at the discretion of the treating physician, guided by the local NICU criteria for mechanical ventilation.
Secondary outcomes are listed under Outcome Measures.
SAMPLE SIZE
According to a baseline study conducted in 2023 (unpublished data), we assume that 21,5% of neonates in the control group (INSURE) would meet failure criteria. If there is no difference between SALSA and INSURE in terms of use of IMV (21,5% in both arms), 418 neonates need to be enrolled to be 80% sure that the upper limit of a one-sided 95% confidence interval will exclude an absolute difference larger than 10% in favour of INSURE. The sample is increased to 440 neonates to take into account a dropout of 5%.
PILOT PHASE
The trial will begin with an internal pilot phase designed to assess the feasibility of recruitment, adherence to trial procedures, data completeness, and intervention fidelity. Efficacy will not be evaluated. The internal pilot phase will enrol 100 neonates (approximately 23% of the total sample size), with recruitment anticipated over 12 months. This design will allow feedback on recruitment capacity and process quality and enabling adaptations.
The pilot phase will assess outcomes related to recruitment feasibility, adherence to intervention, adherence to mechanical ventilation criteria, retention, data completeness, data integrity and acceptability. Pilot outcomes are listed under Outcome Measures.
An interim assessment will be performed after the enrolment of 50 participants or after 12 months, whichever comes first. Only pilot outcomes will be assessed. The final analysis of the pilot phase will take place upon completion of enrolment of 100 participants. Following this evaluation, the Trial Steering Committee will determine whether to continue the study without modifications, implement protocol amendments-such as the inclusion of additional trial sites or adjustments to trial procedures-or temporarily suspend the trial to allow for a redesign. These decisions will be guided by a balanced assessment across all pilot domains.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Investigator-initiated, single-centre, two-arm parallel-group, open-label, non-inferiority RCT with a 1:1 allocation ratio per neonate. The trial entails an internal pilot-phase of the first 100 patients.
| Arm | Type | Receives |
|---|---|---|
| Surfactant therapy administered via supraglottic airway device (SALSA) | Experimental | Procedure: Surfactant Administration Through Laryngeal or Supraglottic Airways (SALSA)Study participants will receive surfactant therapy via a preterm size supraglottic airway device (SALSA). |
| Endotracheal intubation - surfactant administration - and extubation (INSURE) | Active comparator | Procedure: Intubation - Surfactant administration - Extubation (INSURE)Study participants will receive surfactant therapy administered via brief endotracheal intubation - surfactant administration - and extubation (INSURE). |
Who may qualify
- Ages
- Up to 48 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Inborn neonate (=born in the hospital), AND
- Gestational age <34+0 weeks, AND
- Birth weight ≥750g, AND
- Age <48 hours, AND
- Diagnosis of RDS, confirmed with a chest x-ray or lung ultrasound, except in cases where immediate treatment is necessary and imaging would cause a delay AND
Key exclusion criteria (9 listed)
- Severe respiratory insufficiency in need of intubation at delivery room
- Severe respiratory insufficiency in need of intubation and invasive mechanical ventilation after arrival to NICU
- Previous surfactant administration
- Previous invasive mechanical ventilation
- Known pneumothorax
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Surfactant Administration Through Laryngeal or Supraglottic Airways (SALSA)Also: Laryngeal mask airway surfactant administration, Surfactant Therapy via Laryngeal Mask Airway, Laryngeal Mask Airway for Surfactant Administration in Neonates, Supraglottic airway devices for surfactant treatmentWhile the infant is spontaneously breathing on nasal CPAP, the NICU physician will place the supraglottic airway device (SAD) and assess airway adequacy via CO₂ detection, chest movement, bilateral breath sounds, gastric insufflation, oxygen saturation, and heart rate. Each placement attempt should last no more than 30 seconds, with up to two attempts allowed. Surfactant (Curosurf 200 mg/kg) will be given slowly in 1-2 ml aliquots via a CE-marked preterm-sized SAD, Neo i-gel® (sizes 0.85, 0.75, 0.65; Intersurgical Ltd). The infant should primarily breathe spontaneously with PEEP from a T-piece resuscitator and receive gentle PPV if needed. PPV is continued for 30 seconds after surfactant administration before SAD removal. A reservoir bag may be used secondarily to provide PPV. If surfactant delivery via SALSA fails, the INSURE method (Intubation-Surfactant-Extubation) will be attempted. | Procedure or surgery | Surfactant therapy administered via supraglottic airway device (SALSA) |
| Intubation - Surfactant administration - Extubation (INSURE)Study participants will receive surfactant therapy administered via brief endotracheal intubation - surfactant administration - and extubation (INSURE). Infants will be ventilated using a T-piece resuscitator with PEEP of 6 cm H20 and positive pressure ventilation (20 cm H20) for a couple of minutes (no more than 15 minutes) with adjustable FiO2. No mechanical ventilation will be used. Secondarily a reservoir-bag will be used for ventilation. | Procedure or surgery | Endotracheal intubation - surfactant administration - and extubation (INSURE) |
Primary outcome
Failure of surfactant therapy to prevent invasive mechanical ventilation
Time frame: Within 72 hours after first surfactant administration
Categorical variable (Yes/No). Failure in terms of the need for endotracheal intubation and invasive mechanical ventilation. Decision to initiate mechanical ventilation via intubation will be made at the discretion of the treating physician, guided by the local NICU criteria for mechanical ventilation. Data is extracted from medical records. Analysis considerations: * If an infant deteriorates after randomization and requires intubation with mechanical ventilation before the allocated intervention can be performed, the case will be classified as failure in the intention-to-treat (ITT) analysis, but excluded from the per-protocol (PP) analysis. * If an infant improves after randomization and the allocated intervention is not required, the case will be included and not considered a failure in the ITT analysis, but excluded from the PP analysis.
36 secondary outcomes
Early failure of surfactant therapy
Time frame: Within 1 hour after first surfactant administration
Late failure of surfactant therapy
Time frame: Between 1 hour and 72 hours after first surfactant administration
Time to initiation of invasive mechanical ventilation after the procedure
Time frame: Before discharge (about 6-15 weeks)
Invasive mechanical ventilation at any time during admission
Time frame: Before discharge (about 6-15 weeks)
Incidence of severe bradycardia
Time frame: During the procedure, an average of 5-10 minutes
Incidence of severe desaturation
Time frame: During the procedure, an average of 5-10 minutes
Change in FiO₂ (%) from before the procedure to 3 hours after surfactant administration
Time frame: Within 10 minutes before the procedure to 3 hours after first surfactant administration
Number of placement attempts needed to place LMA or ETT
Time frame: During the procedure, an average of 5-10 minutes
Failure to place supraglottic airway device (SAD) or endotracheal tube (ETT) at first attempt
Time frame: During the procedure, an average of 5-10 minutes
Volume of postintervention surfactant-resembling gastric residuals
Time frame: Directly after first surfactant administration
Proportion (%) of postintervention gastric surfactant aspirated of total surfactant dose
Time frame: Directly after first surfactant administration
Postintervention gastric surfactant aspirated greater than 10% of surfactant dose
Time frame: Directly after first surfactant administration
Reflux of surfactant during procedure
Time frame: Directly after first surfactant administration
Number of surfactant doses given during admission
Time frame: Before discharge (about 6-15 weeks)
Administration of a second surfactant dose within 6 hours of the first dose
Time frame: 6 hours after initial dose
Method of subsequent surfactant doses
Time frame: Before discharge (about 6-15 weeks)
Incidence of mortality within 7 days after birth
Time frame: Seven days of age
Incidence of mortality prior to discharge
Time frame: Before discharge (about 6-15 weeks)
Time to death
Time frame: Before discharge (about 6-15 weeks)
Duration of invasive mechanical ventilation
Time frame: Before discharge (about 6-15 weeks)
Duration of Continuous Positive Airway Pressure (CPAP) or Non-invasive Positive Pressure Ventilation (NIPPV)
Time frame: Before discharge (about 6-15 weeks)
Duration of any respiratory support (IMV, CPAP, NIPPV or oxygen by nasal cannula)
Time frame: Before discharge (about 6-15 weeks)
Duration of hospital admission
Time frame: Before discharge (about 6-15 weeks)
Incidence of bronchopulmonary dysplasia
Time frame: 36 weeks post menstrual age
Postnatal steroid treatment before discharge
Time frame: Before discharge (about 6-15 weeks)
Incidence of IVH grade III or IV
Time frame: Before discharge (about 6-15 weeks)
Incidence of cystic periventricular leukomalacia
Time frame: Before discharge (about 6-15 weeks)
Incidence of pneumothorax, requiring drainage
Time frame: Before discharge (about 6-15 weeks)
Incidence of pulmonary haemorrhage, requiring circulatory support
Time frame: Before discharge (about 6-15 weeks)
Incidence of persistent ductus arteriosus requiring treatment
Time frame: Before discharge (about 6-15 weeks)
Incidence of early-onset sepsis
Time frame: Within 72 hours after birth.
Incidence of late-onset sepsis
Time frame: >72 hours after birth to discharge (about 6-15 weeks)
Incidence of retinopathy of prematurity, ≥ grade 3
Time frame: Before discharge (about 6-15 weeks)
Incidence of transfer due to need of intestinal surgery
Time frame: Before discharge (about 6-15 weeks)
Incidence of transfer to higher-level care
Time frame: Before discharge (about 6-15 weeks)
Incidence of major morbidity before discharge
Time frame: Before discharge (about 6-15 weeks)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2026.
- Background: PubMed 35372140Zapata HA, Fort P, Roberts KD, Kaluarachchi DC, Guthrie SO. Surfactant Administration Through Laryngeal or Supraglottic Airways (SALSA): A Viable Method for Low-Income and Middle-Income Countries. Front Pediatr. 2022 Mar 16;10:853831. doi: 10.3389/fped.2022.853831. eCollection 2022.
- Background: PubMed 40610284Dempsey T, Brismar TB, Svensson-Marcial A, Blennow M, Alfven T, Hook SM, Pejovic N. Radiologic evaluation of three smaller-sized supraglottic airway device prototypes for low-birth-weight neonates. Br J Anaesth. 2025 Nov;135(5):1551-1553. doi: 10.1016/j.bja.2025.05.038. Epub 2025 Jul 3. No abstract available.
- Background: PubMed 38270182Abdel-Latif ME, Walker E, Osborn DA. Laryngeal mask airway surfactant administration for prevention of morbidity and mortality in preterm infants with or at risk of respiratory distress syndrome. Cochrane Database Syst Rev. 2024 Jan 25;1(1):CD008309. doi: 10.1002/14651858.CD008309.pub3.
- Feasibility study of SALSA using the same device at the same hospital in infants with birth weigh 750-1500gLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. The datasets used and/or analysed during the current study will be available from the principal investigator on reasonable request after publication of results.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Tobias Alfvén, Professor, M.D, Ph.D principal investigator
Department of Global Public Health, Karolinska Institutet, Solna, Sweden
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Surfactant Administration Through Laryngeal or Supraglottic Airways (SALSA) and Intubation - Surfactant administration - Extubation (INSURE) in people with Respiratory Distress Syndrome in Premature Infant, run by Karolinska Institutet at 1 site in Vietnam.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Vietnam. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tobias Alfvén, Professor, M.D, Ph.D (+46 70 757 80 93, tobias.alfven@ki.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Failure of surfactant therapy to prevent invasive mechanical ventilation (time frame: Within 72 hours after first surfactant administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07098910, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2026.