Clinical trial NCT02907593: Steroids and Surfactant in Extremely Low Gestation Age Infants Dose Escalation Trial
Official title: Steroids and Surfactant in Extremely Low Gestation Age Infants Pilot Dose Escalation Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Bronchopulmonary Dysplasia (BPD)
Keywords: Bronchopulmonary dysplasia
Pulmonary
Surfactant
Steroids
Extremely low gestational age
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
Collaborators: name: Thrasher Research Fund
name: University of Florida
name: Florida Hospital for Children
name: University of California, San Francisco
First posted: 2016-09-20
Enrollment: 25
Sex: ALL
Minimum age (years): 3
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of ELGANs With Clinical and Anti-inflammatory Efficacy of Escalating Doses of Budesonide Determined by Monitoring Respiratory Severity Score (RSS)
timeFrame: 28 days of life for each dosing group
measure: 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.
timeFrame: 28 days of life for each dosing group
Secondary outcomes:
measure: Adverse Events/Subject Safety
timeFrame: Through 28 days of life
measure: Serial Budesonide Levels, Peak
timeFrame: At 15 minutes, 1 and 4 hours after first dose and prior to each additional dose
measure: Serial Budesonide Levels, T 1/2
timeFrame: At 15 minutes, 1 and 4 hours after first dose and prior to each additional dose
measure: Serial Budesonide Levels, AUC
timeFrame: At 15 minutes, 1 and 4 hours after first dose and prior to each additional dose
measure: Respiratory Severity Score: Mean Airway Pressure and Oxygen Requirement at 28 Days of Age
timeFrame: 28 days of life for each dosing group
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Jacksonville
country: United States
facility: University of Florida, Jacksonville
state: Florida
city: Orlando
country: United States
facility: Florida Hospital for Children
state: Florida
city: Portland
country: United States
facility: Oregon Health ans Science University
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt Children's Hospital
state: Tennessee
Study officials:
affiliation: Oregon Health and Science University
name: Cynthia McEvoy, MD, MCR
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.