Steroids and Surfactant in Extremely Low Gestation Age Infants Dose Escalation Trial

NCT02907593 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: SASSIE-001
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 5

Brief Summary

This is a phase I/II open-label study to determine the lowest, safe, effective dose of budesonide given with calfactant as the vehicle.

Conditions

Bronchopulmonary Dysplasia (BPD)

Keywords

Bronchopulmonary dysplasia; Pulmonary; Surfactant; Steroids; Extremely low gestational age

Outcome Measures

Primary Outcomes (2)

• Number of ELGANs With Clinical and Anti-inflammatory Efficacy of Escalating Doses of Budesonide Determined by Monitoring Respiratory Severity Score (RSS)

  Dose escalation will be defined as effective at the dose level in which 5 of 8 infants achieve the following: 1. Extubation within 72 hours of first dose or after \< 3 doses-without re-intubation before 28 days of age 2. RSS on nasal continuous positive airway pressure (NCPAP) \< 1.5 or on nasal cannula Fi02 \<25% at \< 2L/min at 28 days of age, persisting for at least 72 hours. 3. Cumulative supplemental oxygen \< 4.2 from time of enrollment to 28 days of age 4 4. No respiratory support at 28 days, including no supplemental oxygen by nasal cannula AND a \> 50% suppression of the tracheal aspirate interleukin-8 (IL-8) or CCL2 (chemokine ligand 2) at 24-72 hours (or prior to extubation if occurs at \<24 hours after dosing) after the initial dose in 5 of 8 of the infants (this may be a different combination of 5 patients than those who met the above criteria).

  28 days of life for each dosing group

• The Clinical and Anti-inflammatory Efficacy of Escalating Doses of Budesonide Suspended in Calfactant and Given Into the Lungs of ELGANs by Monitoring Tracheal Aspirate Cytokine Levels.

  Number of ELGANS with a clinical AND Cytokine response: a \> 50% suppression of the tracheal aspirate interleukin-8 or chemokine ligand 2 at 24-72 hours (or prior to extubation if occurs at \<24 hours after dosing) after the initial dose in 5 of 8 of the infants

  28 days of life for each dosing group

Secondary Outcomes (5)

• Adverse Events/Subject Safety

  Through 28 days of life

• Serial Budesonide Levels, Peak

  At 15 minutes, 1 and 4 hours after first dose and prior to each additional dose

• Serial Budesonide Levels, T 1/2

  At 15 minutes, 1 and 4 hours after first dose and prior to each additional dose

• Serial Budesonide Levels, AUC

  At 15 minutes, 1 and 4 hours after first dose and prior to each additional dose

• Respiratory Severity Score: Mean Airway Pressure and Oxygen Requirement at 28 Days of Age

  28 days of life for each dosing group

Study Arms (4)

0.025 mg/kg Budesonide

EXPERIMENTAL

0.025 mg/kg Budesonide in Calfactant

Drug: Budesonide in Calfactant

0.050 mg/kg Budesonide

EXPERIMENTAL

0.050 mg/kg Budesonide in Calfactant

Drug: Budesonide in Calfactant

0.10 mg/kg Budesonide

EXPERIMENTAL

0.10 mg/kg Budesonide in Calfactant

Drug: Budesonide in Calfactant

0.15 mg/kg Budesonide

EXPERIMENTAL

0.15 mg/kg Budesonide in Calfactant

Drug: Budesonide in Calfactant

Interventions

Budesonide in Calfactant DRUG

Budesonide in Calfactant

Also known as: pulmicort respule, calfactant, budesonide, 0186-1986-04, infasurf

0.025 mg/kg Budesonide; 0.050 mg/kg Budesonide; 0.10 mg/kg Budesonide; 0.15 mg/kg Budesonide

Eligibility Criteria

• Age: 3 Days - 14 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• \> 23 0/7 and \< 27 6/7 weeks of gestational age based on center's best estimate of due date (using earliest obstetrical ultrasound, last menstrual period, examination, and other pertinent available information)
• Day of life 3-14 from the date and time of delivery, with the date of birth being DOL 0
• Intubated and mechanically ventilated and do not anticipate extubation in next 24 hours

You may not qualify if:

• Serious congenital malformations or chromosomal abnormality
• Likely to be extubated in next 24 hours
• Clinically unstable
• Infants who have received systemic steroids prior to dosing with study medication.
• Infants who have received Indocin, Ibuprofen, or acetaminophen ≤ 96 hours prior to enrollment window ending

Sponsors & Collaborators

• Cynthia McEvoy: lead
• Thrasher Research Fund: collaborator
• University of Florida: collaborator
• Florida Hospital for Children: collaborator
• University of California, San Francisco: collaborator

Study Sites (5)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

University of Florida, Jacksonville

Jacksonville, Florida, 32209, United States

Location

Florida Hospital for Children

Orlando, Florida, 32803, United States

Location

Oregon Health ans Science University

Portland, Oregon, 97239, United States

Location

Vanderbilt Children's Hospital

Nashville, Tennessee, 37232, United States

Location

Related Publications (5)

• Yeh TF, Chen CM, Wu SY, Husan Z, Li TC, Hsieh WS, Tsai CH, Lin HC. Intratracheal Administration of Budesonide/Surfactant to Prevent Bronchopulmonary Dysplasia. Am J Respir Crit Care Med. 2016 Jan 1;193(1):86-95. doi: 10.1164/rccm.201505-0861OC.

  PMID: 26351971 BACKGROUND

• Yeh TF, Lin HC, Chang CH, Wu TS, Su BH, Li TC, Pyati S, Tsai CH. Early intratracheal instillation of budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants: a pilot study. Pediatrics. 2008 May;121(5):e1310-8. doi: 10.1542/peds.2007-1973. Epub 2008 Apr 21.

  PMID: 18426851 BACKGROUND

• Roberts JK, Stockmann C, Dahl MJ, Albertine KH, Egan E, Lin Z, Reilly CA, Ballard PL, Ballard RA, Ward RM. Pharmacokinetics of Budesonide Administered with Surfactant in Premature Lambs: Implications for Neonatal Clinical Trials. Curr Clin Pharmacol. 2016;11(1):53-61. doi: 10.2174/1574884710666150929100210.

  PMID: 26416605 BACKGROUND

• Barrette AM, Roberts JK, Chapin C, Egan EA, Segal MR, Oses-Prieto JA, Chand S, Burlingame AL, Ballard PL. Antiinflammatory Effects of Budesonide in Human Fetal Lung. Am J Respir Cell Mol Biol. 2016 Nov;55(5):623-632. doi: 10.1165/rcmb.2016-0068OC.

  PMID: 27281349 BACKGROUND

• McEvoy CT, Ballard PL, Ward RM, Rower JE, Wadhawan R, Hudak ML, Weitkamp JH, Harris J, Asselin J, Chapin C, Ballard RA. Dose-escalation trial of budesonide in surfactant for prevention of bronchopulmonary dysplasia in extremely low gestational age high-risk newborns (SASSIE). Pediatr Res. 2020 Oct;88(4):629-636. doi: 10.1038/s41390-020-0792-y. Epub 2020 Feb 1.

  PMID: 32006953 RESULT

MeSH Terms

Conditions

Bronchopulmonary Dysplasia

Interventions

Budesonide; calfactant

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

Early termination of the study is not due to any safety concerns, but rather enrollment challenges and lack of response in patients. The FDA and IRB were notified and approved.

Results Point of Contact

• Title: Dr. Cindy McEvoy
• Organization: Oregon Health & Science University

mcevoyc@ohsu.edu

5034945598

Study Officials

• Cynthia McEvoy, MD, MCR

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Professor of Pediatrics

Study Record Dates

• First Submitted: August 2, 2016
• First Posted: September 20, 2016
• Study Start: September 1, 2016
• Primary Completion: April 1, 2018
• Study Completion: April 1, 2018
• Last Updated: April 4, 2025
• Results First Posted: April 4, 2025

Record last verified: 2025-03

Locations

US (5)