Aerosolized Surfactant in Neonatal RDS

NCT02294630 | Completed Phase 1 Results DMC

• 3 other identifiers: 12060110231R01FD004793-01A1FD004793
• Study Type: interventional
• Target: 159
• Locations: 1 country
• Sites: 1

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.

Conditions

Respiratory Distress Syndrome, Newborn

Outcome Measures

Primary Outcomes (3)

• 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

Secondary Outcomes (18)

• Blood Gas Parameters - pH

  60±30 minutes after end of study intervention

• Blood Gas Parameters - pCO2

  60±30 minutes after end of study intervention

• Pulse Oximetry

  60±30 minutes after end of study intervention

• Vital Signs - Heart Rate

  60±30 minutes after end of study intervention

• Vital Signs - Respiratory Rate

  60±30 minutes after end of study intervention

Study Arms (4)

Dose Schedule I

ACTIVE COMPARATOR

Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant Dilution 1:1

Drug: Surfactant

Dose Schedule II

ACTIVE COMPARATOR

Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant Dilution 1:2

Drug: Surfactant

Dose Schedule III

ACTIVE COMPARATOR

Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant Dilution 1:1

Drug: Surfactant

Dose Schedule IV

ACTIVE COMPARATOR

Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant Dilution 1:2

Drug: Surfactant

Interventions

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.

Also known as: Survanta

Dose Schedule I; Dose Schedule II; Dose Schedule III; Dose Schedule IV

Eligibility Criteria

• Age: Up to 24 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Infants admitted to the NICU at Hutzel Women's Hospital (HWH)/Children's Hospital of Michigan (CHM)
• Gestational age of 240/7-366/7 weeks
• Postnatal age ≤ 24 hours
• Respiratory support with NIV (CPAP or NIPPV or HFNC) with FiO2 ≥25% or PEEP ≥ 4 cmH20 or HFNC rate ≥ 2 LPM for ≤8 hours
• Written informed consent from parent/guardian

You may not qualify if:

• Previous receipt of surfactant
• Infants with respiratory distress who are unstable and require immediate intubation
• Active air leak syndrome (e.g. pneumothorax, pneumomediastinum)
• Lethal congenital malformations; death anticipated within first 3 days of life; decision to withhold support
• Serious abdominal, cardiac, airway or respiratory malformations including tracheal esophageal fistula, intestinal atresia, omphalocele, gastroschisis, pulmonary hypoplasia, or diaphragmatic hernia
• Neuromuscular disorder resulting in respiratory compromise

Sponsors & Collaborators

• Sood, Beena G., MD, MS: lead

Study Sites (1)

Hutzel Women's Hospital

Detroit, Michigan, 48201, United States

Location

Related Publications (2)

• 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.

  PMID: 31121339 BACKGROUND

• 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.

  PMID: 33338661 RESULT

MeSH Terms

Conditions

Respiratory Distress Syndrome, Newborn

Interventions

Surface-Active Agents; beractant

Condition Hierarchy (Ancestors)

Respiratory Distress Syndrome; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Specialty Uses of Chemicals; Chemical Actions and Uses

Results Point of Contact

• Title: Beena G. Sood, MD, MS
• Organization: Wayne State University

bsood@med.wayne.edu

313-745-5638

Study Officials

• Beena G. Sood, MD, MS

  Wayne State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2014
• First Posted: November 19, 2014
• Study Start: December 1, 2014
• Primary Completion: July 1, 2019
• Study Completion: July 1, 2020
• Last Updated: August 25, 2021
• Results First Posted: August 25, 2021

Record last verified: 2021-07

Locations

US (1)