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

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

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

Study Overview

• Status: Terminated
• Conditions: Bronchopulmonary Dysplasia (BPD)
• Intervention / Treatment: Drug: Budesonide in Calfactant

Detailed Description

This is a phase I/II open-label study to determine the lowest safe, effective dose of budesonide given with calfactant as the vehicle; the investigators will perform an unblinded dose escalation study. The investigators will administer four dosing levels of budesonide suspended in calfactant beginning with 0.025 mg/kg of budesonide administered to 8 extremely low gestational age newborns (ELGANs) who are intubated at 3-10 days of age. Daily doses (at the same dosage) will be administered to infants who remain intubated for a potential of 5 total doses in each patient. Subsequent groups of 8 infants each will receive 0.05 mg/kg, 0.10 mg/kg, and 0.15 mg/kg of budesonide in calfactant (up to 5 total doses in each patient). A total of up to 32 infants will be enrolled in the trial. The investigators will evaluate the clinical, laboratory and safety data from each group of treated infants to 28 days of age before moving to the next dosing level of budesonide.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida, Jacksonville
    • Orlando, Florida, United States, 32803
      • Florida Hospital for Children
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health ans Science University
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 days to 2 weeks (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. > 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)
2. Day of life 3-14 from the date and time of delivery, with the date of birth being DOL 0
3. Intubated and mechanically ventilated and do not anticipate extubation in next 24 hours

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.025 mg/kg Budesonide; 0.025 mg/kg Budesonide in Calfactant	Drug: Budesonide in Calfactant; Budesonide in Calfactant; Other Names: budesonide; pulmicort respule; calfactant; 0186-1986-04; infasurf
Experimental: 0.050 mg/kg Budesonide; 0.050 mg/kg Budesonide in Calfactant	Drug: Budesonide in Calfactant; Budesonide in Calfactant; Other Names: budesonide; pulmicort respule; calfactant; 0186-1986-04; infasurf
Experimental: 0.10 mg/kg Budesonide; 0.10 mg/kg Budesonide in Calfactant	Drug: Budesonide in Calfactant; Budesonide in Calfactant; Other Names: budesonide; pulmicort respule; calfactant; 0186-1986-04; infasurf
Experimental: 0.15 mg/kg Budesonide; 0.15 mg/kg Budesonide in Calfactant	Drug: Budesonide in Calfactant; Budesonide in Calfactant; Other Names: budesonide; pulmicort respule; calfactant; 0186-1986-04; infasurf

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: Extubation within 72 hours of first dose or after < 3 doses-without re-intubation before 28 days of age; 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.; Cumulative supplemental oxygen < 4.2 from time of enrollment to 28 days of age 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events/Subject Safety	Safety assessments will include the subject's vital signs, clinical laboratory testing, morbidities associated with prematurity, morbidities associated with administration of budesonide in calfactant, and Adverse Events (AE)s. Clinical parameters/ AEs of interest are those potentially consistent with elevated glucocorticoid levels and will be specifically evaluated. A Data and Safety Monitoring Board (DSMB) will be established to review safety data. All of the data will be reviewed to monitor subject safety.	Through 28 days of life
Serial Budesonide Levels, Peak	The research team will obtain dried blood spot samples at 15 minutes, and 1 and 4 hours after the first dose of budesonide in calfactant for budesonide levels. Trough concentrations (Cmin) will be drawn before potential subsequent daily doses.	At 15 minutes, 1 and 4 hours after first dose and prior to each additional dose
Serial Budesonide Levels, T 1/2	The research team will obtain dried blood spot samples at 15 minutes, and 1 and 4 hours after the first dose of budesonide in calfactant for budesonide levels. Trough concentrations (Cmin) will be drawn before potential subsequent daily doses.	At 15 minutes, 1 and 4 hours after first dose and prior to each additional dose
Serial Budesonide Levels, AUC	The research team will obtain dried blood spot samples at 15 minutes, and 1 and 4 hours after the first dose of budesonide in calfactant for budesonide levels. Trough concentrations (Cmin) will be drawn before potential subsequent daily doses.	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	Clinical respiratory status (RSS and oxygen requirement) around dosing and at 28 days of age will be compared between dosing groups and also compared to the matched historical control patients from the "Trial of Late Surfactant:(TOLSURF) study. The respiratory severity score (RSS) is a simplified severity score consisting of the mean airway pressure (MAP) multiplied by the fraction of inspired oxygen (FiO2). This score ranges from 0 to 12, with a higher score indicating more severe disease.	28 days of life for each dosing group

Collaborators and Investigators

• Sponsor: Cynthia McEvoy
• Collaborators: University of Florida; University of California, San Francisco; Thrasher Research Fund; Florida Hospital for Children
• Investigators: Principal Investigator: Cynthia McEvoy, MD, MCR, Oregon Health and Science University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: August 2, 2016
• First Submitted That Met QC Criteria: September 14, 2016
• First Posted (Estimated): September 20, 2016

Study Record Updates

• Last Update Posted (Actual): April 4, 2025
• Last Update Submitted That Met QC Criteria: March 20, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Pulmonary; Bronchopulmonary dysplasia; Surfactant; Steroids; Extremely low gestational age
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury; Ventilator-Induced Lung Injury; Bronchopulmonary Dysplasia; Physiological Effects of Drugs; Anti-Inflammatory Agents; Autonomic Agents; Peripheral Nervous System Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Respiratory System Agents; Anti-Asthmatic Agents; Bronchodilator Agents; Pulmonary Surfactants; Budesonide; Calfactant
• Other Study ID Numbers: SASSIE-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No