AS-02: Aerosolized Surfactant in Neonatal RDS

• Sponsor: Sood, Beena G., MD, MS (Other)
• Overall Status: Completed
• CT.gov ID: NCT02294630
• Collaborator: (none)
• Enrollment: 159
• Location: 1
• Arms: 4
• Duration (Months): 67
• Patients Per Site Per Month: 2.4

Study Details

Study Description

Brief Summary

Respiratory distress syndrome (RDS), caused by surfactant deficiency, is the leading cause of mortality and morbidity in preterm infants. Intratracheal instillation, the only approved means of surfactant delivery, requires endotracheal intubation and mechanical ventilation with their attendant risks. Interventions that decrease need for intubation and mechanical ventilation like noninvasive ventilation (NIV) including nasal continuous positive airway pressure, high flow nasal cannula or nasal intermittent mandatory ventilation are increasingly being used for initial respiratory support in preterm neonates with RDS to improve outcomes. Aerosolized surfactant delivered during NIV is an innovative and promising concept for the treatment of RDS - retaining the advantages of early surfactant with alveolar recruitment while obviating the risks of intubation and mechanical ventilation. The investigators overall hypothesis is that treatment of RDS with aerosolized surfactant in preterm infants undergoing NIV is safe and feasible and will result in short-term improvement in oxygenation and ventilation. The objective of this proposal is to perform a single-center unblinded Phase II randomized clinical trial of aerosolized surfactant for the treatment of RDS in preterm neonates undergoing NIV. Funding Source - FDA-OOPD.

Condition or Disease	Intervention/Treatment	Phase
Respiratory Distress Syndrome, Newborn	Drug: Surfactant	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 159 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Aerosolized Survanta in Neonatal Respiratory Distress Syndrome: Phase I/II Study
• Study Start Date: Dec 1, 2014
• Actual Primary Completion Date: Jul 1, 2019
• Actual Study Completion Date: Jul 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Dose Schedule I Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant Dilution 1:1	Drug: Surfactant; Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.; Other Names: Survanta
Active Comparator: Dose Schedule II Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant Dilution 1:2	Drug: Surfactant; Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.; Other Names: Survanta
Active Comparator: Dose Schedule III Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant Dilution 1:1	Drug: Surfactant; Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.; Other Names: Survanta
Active Comparator: Dose Schedule IV Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant Dilution 1:2	Drug: Surfactant; Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.; Other Names: Survanta

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events as a Measure of Safety and Feasibility [During and within 6 hours after end of study drug administration, expected maximum of approximately 14 hours]

   Since surfactant reflux is typically considered to be one of the most likely adverse events associated with the intervention, it was planned to report the number of participants specifically with surfactant reflux for this Outcome Measure

2. Patient Status as Evaluated by Dose Level [During study drug administration, expected maximum of approximately 8 hours for adverse effects and infant comfort; need for intubation was assessed within 72 hours of study intervention.]

   Optimal dosing schedule was determined by preliminary evidence of efficacy (Need for intubation within 72 hours), lack of adverse effects, and overall infant comfort as assessed by bedside clinical caregivers.

3. Short Term Efficacy as Assessed by Need for Intubation [Within 72 hours of study intervention]

   It will be suggested that infants be intubated and receive MV if they met 2 or more of 5 failure criteria: i). worsening clinical signs of respiratory distress (increasing tachypnea; expiratory grunting; intercostal, subcostal, and/or sternal recession); ii). apnea treated with positive pressure ventilation (PPV) by mask on 2 or more occasions in 1 hour; iii). FIO2 >0.5 to maintain pulse oxygen saturations 90%-95% for >30 minutes; iv). pH <7.2 on 2 arterial or capillary blood gases taken >30 minutes apart; and v). partial pressure of CO2 (PCO2) of >65 mm Hg on 2 CBG/ABGs taken 30 minutes apart.

Secondary Outcome Measures

1. Blood Gas Parameters - pH [60±30 minutes after end of study intervention]

   Blood gas pH

2. Blood Gas Parameters - pCO2 [60±30 minutes after end of study intervention]

   Blood gas pCO2.

3. Pulse Oximetry [60±30 minutes after end of study intervention]

   Transcutaneous Pulse oximetry

4. Vital Signs - Heart Rate [60±30 minutes after end of study intervention]

   Vital signs included heart rate, respiratory rate and systolic blood pressure

5. Vital Signs - Respiratory Rate [60±30 minutes after end of study intervention]

   Vital signs included heart rate, respiratory rate and systolic blood pressure

6. Vital Signs - Systolic Blood Pressure [60±30 minutes after end of study intervention]

   Systolic blood pressure

7. Number of Doses of Surfactant - Aerosolized & Intratracheal [Within 72 hours of study intervention]

8. Pneumothorax, Pneumomediastinum or Other Air Leak [Within 72 hours of study intervention]

9. Changes in Cerebral Oxygenation From Baseline as Evaluated at End of Study Intervention [During and within 6 hours after end of study intervention, expected maximum of approximately 14 hours]

   Changes in cerebral oxygenation from baseline as evaluated at end of study intervention

10. Changes in Surfactant Activity in Gastric Aspirates [During study intervention, expected maximum of approximately 8 hours]

    Concentration of major surfactant lipid (PC 16:0/16:0)

11. Cumulative Duration of Non-invasive and Invasive Ventilation [at discharge]

    Cumulative duration of non-invasive and invasive ventilation at discharge

12. Duration of Supplemental Oxygen, Intensive Care, Hospital Stay [During initial hospital stay, expected <= 120 days]

    Duration of supplemental oxygen, and hospital stay

13. Age at Start of Feeds, Feeding Progression, Age at Full Enteral Feeds [During initial hospital stay, expected 1st 2 weeks of life]

    Age at start of feeds, and age at full enteral feeds presented in days

14. Need for Blood Transfusions [During initial hospital stay, expected <= 120 days]

    Number of infants requiring blood transfusions

15. Growth Parameters [At 7 days, 28 days, 36 weeks corrected GA and discharge]

    Weight at discharge

16. Morbidities Associated With Prematurity [During initial hospital stay, expected <= 120 days]

    Grade III & IV IVH PDA requiring ligation ROP treated with Laser Surgical NEC BPD

17. Survival to Hospital Discharge [During initial hospital stay, expected <= 120 days]

    Survival to hospital discharge

18. Survival to Discharge Without Severe Morbidity [During initial hospital stay, expected <= 120 days]

    Survival to discharge without severe BPD, severe IVH, surgical NEC or ROP treated with Laser

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 24 Hours
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Infants admitted to the NICU at Hutzel Women's Hospital (HWH)/Children's Hospital of Michigan (CHM)

2. Gestational age of 240/7-366/7 weeks

3. Postnatal age ≤ 24 hours

4. Clinical diagnosis of RDS based on (i) presence of at least two of the four classic symptoms (need of supplemental oxygen, tachypnea, intercostal retractions or grunting), and (ii) exclusion of other causes of respiratory failure and (iii) Clinician intent to administer surfactant if infant requires intubation

5. Respiratory support with NIV (CPAP or NIPPV or HFNC) with FiO2 ≥25% or PEEP ≥ 4 cmH20 or HFNC rate ≥ 2 LPM for ≤8 hours

6. Written informed consent from parent/guardian

Exclusion Criteria:

1. Previous receipt of surfactant

2. Infants with respiratory distress who are unstable and require immediate intubation

3. Active air leak syndrome (e.g. pneumothorax, pneumomediastinum)

4. Lethal congenital malformations; death anticipated within first 3 days of life; decision to withhold support

5. Serious abdominal, cardiac, airway or respiratory malformations including tracheal esophageal fistula, intestinal atresia, omphalocele, gastroschisis, pulmonary hypoplasia, or diaphragmatic hernia

6. Neuromuscular disorder resulting in respiratory compromise

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hutzel Women's Hospital	Detroit	Michigan	United States	48201

Sponsors and Collaborators

• Sood, Beena G., MD, MS

Investigators

• Principal Investigator: Beena G. Sood, MD, MS, Wayne State University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 31, 2017

More Information

Publications

• Sood BG, Cortez J, Kolli M, Sharma A, Delaney-Black V, Chen X. Aerosolized surfactant in neonatal respiratory distress syndrome: Phase I study. Early Hum Dev. 2019 Jul;134:19-25. doi: 10.1016/j.earlhumdev.2019.05.005. Epub 2019 May 20.

• Responsible Party: Sood, Beena G., MD, MS
• ClinicalTrials.gov Identifier: NCT02294630
• Other Study ID Numbers: 1206011023; 1R01FD004793-01A1; FD004793
• First Posted: Nov 19, 2014
• Last Update Posted: Aug 25, 2021
• Last Verified: Jul 1, 2021

• Additional relevant MeSH terms: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Syndrome; Pulmonary Surfactants

Study Results

Participant Flow

Pre-assignment Detail	Of 159 enrolled and randomized participants, 149 met eligibility criteria and proceeded with treatment.

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Period Title: Overall Study
STARTED	37	38	35	39
COMPLETED	37	38	35	39
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV	Total
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Total of all reporting groups
Overall Participants	37	38	35	39	149
Age (weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [weeks]	31.4 (3.0)	31.6 (3.3)	31.0 (3.0)	31.7 (3.2)	31.4 (3.1)
Age, Customized (Count of Participants)
GA strata I (24-28 weeks)	7 18.9%	7 18.4%	8 22.9%	7 17.9%	29 19.5%
GA strata II (29-32 weeks)	16 43.2%	15 39.5%	14 40%	15 38.5%	60 40.3%
GA strata III (33-36 weeks)	14 37.8%	16 42.1%	13 37.1%	17 43.6%	60 40.3%
Sex: Female, Male (Count of Participants)
Female	20 54.1%	24 63.2%	20 57.1%	14 35.9%	78 52.3%
Male	17 45.9%	14 36.8%	15 42.9%	25 64.1%	71 47.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	2 5.3%	1 2.9%	1 2.6%	4 2.7%
Not Hispanic or Latino	37 100%	35 92.1%	33 94.3%	36 92.3%	141 94.6%
Unknown or Not Reported	0 0%	1 2.6%	1 2.9%	2 5.1%	4 2.7%
Region of Enrollment (Count of Participants)
United States	37 100%	38 100%	35 100%	39 100%	149 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events as a Measure of Safety and Feasibility
Description	Since surfactant reflux is typically considered to be one of the most likely adverse events associated with the intervention, it was planned to report the number of participants specifically with surfactant reflux for this Outcome Measure
Time Frame	During and within 6 hours after end of study drug administration, expected maximum of approximately 14 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Measure Participants	37	38	35	39
Count of Participants [Participants]	3 8.1%	8 21.1%	4 11.4%	12 30.8%

2. Primary Outcome

Title	Patient Status as Evaluated by Dose Level
Description	Optimal dosing schedule was determined by preliminary evidence of efficacy (Need for intubation within 72 hours), lack of adverse effects, and overall infant comfort as assessed by bedside clinical caregivers.
Time Frame	During study drug administration, expected maximum of approximately 8 hours for adverse effects and infant comfort; need for intubation was assessed within 72 hours of study intervention.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Measure Participants	37	38	35	39
Need for Intubation within 72 hours	3 8.1%	3 7.9%	5 14.3%	4 10.3%
Adverse events - surfactant reflux	3 8.1%	8 21.1%	4 11.4%	12 30.8%
Overall infant comfort during AS as assessed by bedside nurse (infant most comfortable)	30 81.1%	27 71.1%	26 74.3%	26 66.7%

3. Primary Outcome

Title	Short Term Efficacy as Assessed by Need for Intubation
Description	It will be suggested that infants be intubated and receive MV if they met 2 or more of 5 failure criteria: i). worsening clinical signs of respiratory distress (increasing tachypnea; expiratory grunting; intercostal, subcostal, and/or sternal recession); ii). apnea treated with positive pressure ventilation (PPV) by mask on 2 or more occasions in 1 hour; iii). FIO2 >0.5 to maintain pulse oxygen saturations 90%-95% for >30 minutes; iv). pH <7.2 on 2 arterial or capillary blood gases taken >30 minutes apart; and v). partial pressure of CO2 (PCO2) of >65 mm Hg on 2 CBG/ABGs taken 30 minutes apart.
Time Frame	Within 72 hours of study intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Measure Participants	37	38	35	39
Count of Participants [Participants]	3 8.1%	3 7.9%	5 14.3%	4 10.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dose Schedule I, Dose Schedule II
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.399
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Blood Gas Parameters - pH
Description	Blood gas pH
Time Frame	60±30 minutes after end of study intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Measure Participants	37	38	34	39
Mean (Standard Deviation) [pH units for pH, mmHg for pCO2]	7.35 (0.05)	7.36 (0.07)	7.36 (0.06)	7.35 (0.05)

5. Secondary Outcome

Title	Blood Gas Parameters - pCO2
Description	Blood gas pCO2.
Time Frame	60±30 minutes after end of study intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Measure Participants	37	38	35	39
Mean (Standard Deviation) [mmHg]	45 (8)	45 (9)	43 (6)	45 (7)

6. Secondary Outcome

Title	Pulse Oximetry
Description	Transcutaneous Pulse oximetry
Time Frame	60±30 minutes after end of study intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Measure Participants	37	38	35	39
Mean (Standard Deviation) [percentage of oxygen saturation]	95.95 (3.34)	96.95 (5.22)	97.37 (3.16)	97.47 (3.07)

7. Secondary Outcome

Title	Vital Signs - Heart Rate
Description	Vital signs included heart rate, respiratory rate and systolic blood pressure
Time Frame	60±30 minutes after end of study intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Measure Participants	37	38	35	39
Mean (Standard Deviation) [beats/minute]	134 (12)	142 (14)	138 (12)	136 (12)

8. Secondary Outcome

Title	Vital Signs - Respiratory Rate
Description	Vital signs included heart rate, respiratory rate and systolic blood pressure
Time Frame	60±30 minutes after end of study intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Measure Participants	37	38	35	39
Mean (Standard Deviation) [breaths/minute]	47 (17)	47 (15)	46 (15)	47 (15)

9. Secondary Outcome

Title	Vital Signs - Systolic Blood Pressure
Description	Systolic blood pressure
Time Frame	60±30 minutes after end of study intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Measure Participants	37	38	35	39
Mean (Standard Deviation) [mmHg]	54 (9)	51 (8)	54 (10)	53 (9)

10. Secondary Outcome

Title	Number of Doses of Surfactant - Aerosolized & Intratracheal
Time Frame	Within 72 hours of study intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Measure Participants	37	38	35	39
One dose of aerosolized surfactant	10 27%	14 36.8%	13 37.1%	14 35.9%
Two doses of aerosolized surfactant	27 73%	24 63.2%	22 62.9%	25 64.1%
No. of doses of intratracheal surfactant - one	0 0%	2 5.3%	2 5.7%	0 0%
No. of doses of intratracheal surfactant - two	2 5.4%	0 0%	1 2.9%	1 2.6%
No. of doses of intratracheal surfactant - three	0 0%	0 0%	1 2.9%	2 5.1%
No. of doses of intratracheal surfactant - four	0 0%	1 2.6%	0 0%	0 0%

11. Secondary Outcome

Title	Pneumothorax, Pneumomediastinum or Other Air Leak
Time Frame	Within 72 hours of study intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Measure Participants	37	38	35	39
Count of Participants [Participants]	0 0%	1 2.6%	0 0%	1 2.6%

12. Secondary Outcome

Title	Changes in Cerebral Oxygenation From Baseline as Evaluated at End of Study Intervention
Description	Changes in cerebral oxygenation from baseline as evaluated at end of study intervention
Time Frame	During and within 6 hours after end of study intervention, expected maximum of approximately 14 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Measure Participants	35	36	33	38
Mean (Standard Deviation) [percentage of oxygen saturation]	79 (8)	80 (8)	78 (11)	79 (8)

13. Secondary Outcome

Title	Changes in Surfactant Activity in Gastric Aspirates
Description	Concentration of major surfactant lipid (PC 16:0/16:0)
Time Frame	During study intervention, expected maximum of approximately 8 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Measure Participants	22	24	22	23
Mean (Standard Deviation) [ng per mg of protein]	10.9 (14.6)	9.5 (9.2)	8.8 (7.8)	8.0 (8.0)

14. Secondary Outcome

Title	Cumulative Duration of Non-invasive and Invasive Ventilation
Description	Cumulative duration of non-invasive and invasive ventilation at discharge
Time Frame	at discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Measure Participants	37	38	35	39
Duration of NIV (days)	4.5 (8.1)	7.0 (14.6)	7.9 (14.2)	6.1 (14.7)
Duration of Invasive ventilation (days)	1.3 (5.1)	0.9 (4.0)	1.6 (5.1)	2.2 (7.4)

15. Secondary Outcome

Title	Duration of Supplemental Oxygen, Intensive Care, Hospital Stay
Description	Duration of supplemental oxygen, and hospital stay
Time Frame	During initial hospital stay, expected <= 120 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Measure Participants	37	38	35	39
Duration of supplemental oxygen (days)	7.4 (18.5)	9.0 (22.9)	10.7 (25.2)	8.9 (29.3)
Length of hospital stay (days)	29.9 (28)	26.4 (24.3)	32.1 (29.9)	28.3 (30.8)

16. Secondary Outcome

Title	Age at Start of Feeds, Feeding Progression, Age at Full Enteral Feeds
Description	Age at start of feeds, and age at full enteral feeds presented in days
Time Frame	During initial hospital stay, expected 1st 2 weeks of life

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Measure Participants	37	36	34	39
Age at start of feeds (days)	1.3 (.7)	1.6 (1.7)	1.8 (1.7)	1.5 (1.1)
Age at full enteral feeds (days)	11.2 (8.8)	7.8 (7.3)	11.8 (11.7)	12.9 (12.9)

17. Secondary Outcome

Title	Need for Blood Transfusions
Description	Number of infants requiring blood transfusions
Time Frame	During initial hospital stay, expected <= 120 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Measure Participants	37	38	35	39
Count of Participants [Participants]	10 27%	6 15.8%	8 22.9%	7 17.9%

18. Secondary Outcome

Title	Growth Parameters
Description	Weight at discharge
Time Frame	At 7 days, 28 days, 36 weeks corrected GA and discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Measure Participants	37	38	35	39
Mean (Standard Deviation) [grams]	2153 (458)	2222 (431)	2235 (561)	2281 (522)

19. Secondary Outcome

Title	Morbidities Associated With Prematurity
Description	Grade III & IV IVH PDA requiring ligation ROP treated with Laser Surgical NEC BPD
Time Frame	During initial hospital stay, expected <= 120 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Measure Participants	37	38	35	39
Grade III & IV IVH	0 0%	1 2.6%	0 0%	1 2.6%
PDA requiring ligation	0 0%	1 2.6%	0 0%	0 0%
ROP treated with Laser	0 0%	1 2.6%	0 0%	1 2.6%
Surgical NEC	0 0%	0 0%	2 5.7%	2 5.1%
BPD	4 10.8%	4 10.5%	5 14.3%	2 5.1%

20. Secondary Outcome

Title	Survival to Hospital Discharge
Description	Survival to hospital discharge
Time Frame	During initial hospital stay, expected <= 120 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Measure Participants	37	38	35	39
Count of Participants [Participants]	37 100%	38 100%	35 100%	39 100%

21. Secondary Outcome

Title	Survival to Discharge Without Severe Morbidity
Description	Survival to discharge without severe BPD, severe IVH, surgical NEC or ROP treated with Laser
Time Frame	During initial hospital stay, expected <= 120 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Schedule I	Dose Schedule II	Dose Schedule III	Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.	Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Measure Participants	37	38	35	39
Count of Participants [Participants]	37 100%	35 92.1%	33 94.3%	35 89.7%

Adverse Events

Time Frame	During and within 6 hours after the end of study drug administration, an expected maximum of approximately 14 hours
Arm/Group Title	Dose Schedule I		Dose Schedule II		Dose Schedule III		Dose Schedule IV
Arm/Group Description	Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.		Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.		Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.		Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
All Cause Mortality
	Dose Schedule I		Dose Schedule II		Dose Schedule III		Dose Schedule IV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/37 (0%)		0/38 (0%)		0/35 (0%)		0/39 (0%)
Serious Adverse Events
	Dose Schedule I		Dose Schedule II		Dose Schedule III		Dose Schedule IV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/37 (0%)		0/38 (0%)		0/35 (0%)		0/39 (0%)
Other (Not Including Serious) Adverse Events
	Dose Schedule I		Dose Schedule II		Dose Schedule III		Dose Schedule IV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/37 (21.6%)		18/38 (47.4%)		12/35 (34.3%)		20/39 (51.3%)
Respiratory, thoracic and mediastinal disorders
Surfactant reflux from nose/mouth	3/37 (8.1%)		8/38 (21.1%)		4/35 (11.4%)		12/39 (30.8%)
Desaturations	2/37 (5.4%)		3/38 (7.9%)		4/35 (11.4%)		7/39 (17.9%)
Plugging of nasal prongs	1/37 (2.7%)		1/38 (2.6%)		1/35 (2.9%)		2/39 (5.1%)
Increased secretions requiring suctioning	1/37 (2.7%)		7/38 (18.4%)		2/35 (5.7%)		0/39 (0%)
Residual surfactant in nasal prongs	0/37 (0%)		0/38 (0%)		1/35 (2.9%)		2/39 (5.1%)
Dislodged prongs	1/37 (2.7%)		1/38 (2.6%)		2/35 (5.7%)		2/39 (5.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.