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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01FD004793-01A1 | U.S. FDA Grant/Contract | View source | |
| FD004793 | Other Identifier | FDA - OOPD |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Schedule I | Active Comparator | Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant Dilution 1:1 |
|
| Dose Schedule II | Active Comparator | Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant Dilution 1:2 |
|
| Dose Schedule III | Active Comparator | Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant Dilution 1:1 |
|
| Dose Schedule IV | Active Comparator | Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant Dilution 1:2 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Surfactant | Drug | 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 | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events as a Measure of Safety and Feasibility | 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 | During and within 6 hours after end of study drug administration, expected maximum of approximately 14 hours |
| Patient Status as Evaluated by Dose Level | 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. | 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. |
| Short Term Efficacy as Assessed by Need for Intubation | 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. | Within 72 hours of study intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Blood Gas Parameters - pH | Blood gas pH | 60±30 minutes after end of study intervention |
| Blood Gas Parameters - pCO2 | Blood gas pCO2. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Beena G. Sood, MD, MS | Wayne State University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hutzel Women's Hospital | Detroit | Michigan | 48201 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31121339 | Background | 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. | |
| 33338661 | Result | Sood BG, Thomas R, Delaney-Black V, Xin Y, Sharma A, Chen X. Aerosolized Beractant in neonatal respiratory distress syndrome: A randomized fixed-dose parallel-arm phase II trial. Pulm Pharmacol Ther. 2021 Feb;66:101986. doi: 10.1016/j.pupt.2020.101986. Epub 2020 Dec 16. |
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Of 159 enrolled and randomized participants, 149 met eligibility criteria and proceeded with treatment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dose Schedule I | 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. |
| FG001 | Dose Schedule II | 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. |
| FG002 | Dose Schedule III | 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. |
| FG003 | Dose Schedule IV | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Dose Schedule I | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Adverse Events as a Measure of Safety and Feasibility | 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 | Posted | Count of Participants | Participants | During and within 6 hours after end of study drug administration, expected maximum of approximately 14 hours |
|
During and within 6 hours after the end of study drug administration, an expected maximum of approximately 14 hours
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dose Schedule I | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Surfactant reflux from nose/mouth | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | Surfactant reflux from nose/mouth |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Beena G. Sood, MD, MS | Wayne State University | 313-745-5638 | bsood@med.wayne.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 31, 2017 | May 12, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D012127 | Respiratory Distress Syndrome, Newborn |
| ID | Term |
|---|---|
| D012128 | Respiratory Distress Syndrome |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
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| ID | Term |
|---|---|
| D013501 | Surface-Active Agents |
| C072197 | beractant |
| ID | Term |
|---|---|
| D020313 | Specialty Uses of Chemicals |
| D020164 | Chemical Actions and Uses |
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|
|
| 60±30 minutes after end of study intervention |
| Pulse Oximetry | Transcutaneous Pulse oximetry | 60±30 minutes after end of study intervention |
| Vital Signs - Heart Rate | Vital signs included heart rate, respiratory rate and systolic blood pressure | 60±30 minutes after end of study intervention |
| Vital Signs - Respiratory Rate | Vital signs included heart rate, respiratory rate and systolic blood pressure | 60±30 minutes after end of study intervention |
| Vital Signs - Systolic Blood Pressure | Systolic blood pressure | 60±30 minutes after end of study intervention |
| Number of Doses of Surfactant - Aerosolized & Intratracheal | Within 72 hours of study intervention |
| Pneumothorax, Pneumomediastinum or Other Air Leak | Within 72 hours of study intervention |
| Changes in Cerebral Oxygenation From Baseline as Evaluated at End of Study Intervention | 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 Surfactant Activity in Gastric Aspirates | Concentration of major surfactant lipid (PC 16:0/16:0) | During study intervention, expected maximum of approximately 8 hours |
| Cumulative Duration of Non-invasive and Invasive Ventilation | Cumulative duration of non-invasive and invasive ventilation at discharge | at discharge |
| Duration of Supplemental Oxygen, Intensive Care, Hospital Stay | Duration of supplemental oxygen, and hospital stay | During initial hospital stay, expected <= 120 days |
| Age at Start of Feeds, Feeding Progression, Age at Full Enteral Feeds | Age at start of feeds, and age at full enteral feeds presented in days | During initial hospital stay, expected 1st 2 weeks of life |
| Need for Blood Transfusions | Number of infants requiring blood transfusions | During initial hospital stay, expected <= 120 days |
| Growth Parameters | Weight at discharge | At 7 days, 28 days, 36 weeks corrected GA and discharge |
| Morbidities Associated With Prematurity | Grade III & IV IVH PDA requiring ligation ROP treated with Laser Surgical NEC BPD | During initial hospital stay, expected <= 120 days |
| Survival to Hospital Discharge | Survival to hospital discharge | During initial hospital stay, expected <= 120 days |
| Survival to Discharge Without Severe Morbidity | Survival to discharge without severe BPD, severe IVH, surgical NEC or ROP treated with Laser | During initial hospital stay, expected <= 120 days |
| BG001 | Dose Schedule II | 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. |
| BG002 | Dose Schedule III | 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. |
| BG003 | Dose Schedule IV | 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. |
| BG004 | Total | Total of all reporting groups |
| weeks |
|
| Age, Customized | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | Dose Schedule II | 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. |
| OG002 | Dose Schedule III | 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. |
| OG003 | Dose Schedule IV | 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. |
|
|
| Primary | Patient Status as Evaluated by Dose Level | 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. | Posted | Count of Participants | Participants | 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. |
|
|
|
| Primary | Short Term Efficacy as Assessed by Need for Intubation | 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. | Posted | Count of Participants | Participants | Within 72 hours of study intervention |
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|
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| Secondary | Blood Gas Parameters - pH | Blood gas pH | Posted | Mean | Standard Deviation | pH units for pH, mmHg for pCO2 | 60±30 minutes after end of study intervention |
|
|
|
| Secondary | Blood Gas Parameters - pCO2 | Blood gas pCO2. | Posted | Mean | Standard Deviation | mmHg | 60±30 minutes after end of study intervention |
|
|
|
| Secondary | Pulse Oximetry | Transcutaneous Pulse oximetry | Posted | Mean | Standard Deviation | percentage of oxygen saturation | 60±30 minutes after end of study intervention |
|
|
|
| Secondary | Vital Signs - Heart Rate | Vital signs included heart rate, respiratory rate and systolic blood pressure | Posted | Mean | Standard Deviation | beats/minute | 60±30 minutes after end of study intervention |
|
|
|
| Secondary | Vital Signs - Respiratory Rate | Vital signs included heart rate, respiratory rate and systolic blood pressure | Posted | Mean | Standard Deviation | breaths/minute | 60±30 minutes after end of study intervention |
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|
|
| Secondary | Vital Signs - Systolic Blood Pressure | Systolic blood pressure | Posted | Mean | Standard Deviation | mmHg | 60±30 minutes after end of study intervention |
|
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| Secondary | Number of Doses of Surfactant - Aerosolized & Intratracheal | Posted | Count of Participants | Participants | Within 72 hours of study intervention |
|
|
|
| Secondary | Pneumothorax, Pneumomediastinum or Other Air Leak | Posted | Count of Participants | Participants | Within 72 hours of study intervention |
|
|
|
| Secondary | Changes in Cerebral Oxygenation From Baseline as Evaluated at End of Study Intervention | Changes in cerebral oxygenation from baseline as evaluated at end of study intervention | Posted | Mean | Standard Deviation | percentage of oxygen saturation | During and within 6 hours after end of study intervention, expected maximum of approximately 14 hours |
|
|
|
| Secondary | Changes in Surfactant Activity in Gastric Aspirates | Concentration of major surfactant lipid (PC 16:0/16:0) | Posted | Mean | Standard Deviation | ng per mg of protein | During study intervention, expected maximum of approximately 8 hours |
|
|
|
| Secondary | Cumulative Duration of Non-invasive and Invasive Ventilation | Cumulative duration of non-invasive and invasive ventilation at discharge | Posted | Mean | Standard Deviation | number of days | at discharge |
|
|
|
| Secondary | Duration of Supplemental Oxygen, Intensive Care, Hospital Stay | Duration of supplemental oxygen, and hospital stay | Posted | Mean | Standard Deviation | number of days | During initial hospital stay, expected <= 120 days |
|
|
|
| Secondary | Age at Start of Feeds, Feeding Progression, Age at Full Enteral Feeds | Age at start of feeds, and age at full enteral feeds presented in days | Posted | Mean | Standard Deviation | age in days | During initial hospital stay, expected 1st 2 weeks of life |
|
|
|
| Secondary | Need for Blood Transfusions | Number of infants requiring blood transfusions | Posted | Count of Participants | Participants | During initial hospital stay, expected <= 120 days |
|
|
|
| Secondary | Growth Parameters | Weight at discharge | Posted | Mean | Standard Deviation | grams | At 7 days, 28 days, 36 weeks corrected GA and discharge |
|
|
|
| Secondary | Morbidities Associated With Prematurity | Grade III & IV IVH PDA requiring ligation ROP treated with Laser Surgical NEC BPD | Posted | Count of Participants | Participants | During initial hospital stay, expected <= 120 days |
|
|
|
| Secondary | Survival to Hospital Discharge | Survival to hospital discharge | Posted | Count of Participants | Participants | During initial hospital stay, expected <= 120 days |
|
|
|
| Secondary | Survival to Discharge Without Severe Morbidity | Survival to discharge without severe BPD, severe IVH, surgical NEC or ROP treated with Laser | Posted | Count of Participants | Participants | During initial hospital stay, expected <= 120 days |
|
|
|
| 0 |
| 37 |
| 0 |
| 37 |
| 8 |
| 37 |
| EG001 | Dose Schedule II | 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. | 0 | 38 | 0 | 38 | 18 | 38 |
| EG002 | Dose Schedule III | 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. | 0 | 35 | 0 | 35 | 12 | 35 |
| EG003 | Dose Schedule IV | 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. | 0 | 39 | 0 | 39 | 20 | 39 |
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| Desaturations | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | Desaturations |
|
| Plugging of nasal prongs | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | Plugging of nasal prongs |
|
| Increased secretions requiring suctioning | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | Increased secretions requiring suctioning |
|
| Residual surfactant in nasal prongs | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | Residual surfactant in nasal prongs |
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| Dislodged prongs | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | Dislodged prongs |
|
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| D007235 | Infant, Premature, Diseases |
| D007232 | Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| Adverse events - surfactant reflux |
|
| Overall infant comfort during AS as assessed by bedside nurse (infant most comfortable) |
|
| Two doses of aerosolized surfactant |
|
| No. of doses of intratracheal surfactant - one |
|
| No. of doses of intratracheal surfactant - two |
|
| No. of doses of intratracheal surfactant - three |
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| No. of doses of intratracheal surfactant - four |
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| Duration of Invasive ventilation (days) |
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| Length of hospital stay (days) |
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| Age at full enteral feeds (days) |
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| PDA requiring ligation |
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| ROP treated with Laser |
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| Surgical NEC |
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| BPD |
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