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

Bronchopulmonary Dysplasia (BPD) Clinical Trial

— SASSIE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02907593
• Other study ID #: SASSIE-001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 2016
• Est. completion date: April 2018

Study information

• Verified date: October 2018
• Source: Oregon Health and Science University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: April 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 14 Days

Eligibility

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

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia
• Bronchopulmonary Dysplasia (BPD)

Intervention

Drug:
• Budesonide in Calfactant
Budesonide in Calfactant

Locations

Country	Name	City	State
United States	University of Florida, Jacksonville	Jacksonville	Florida
United States	Vanderbilt Children's Hospital	Nashville	Tennessee
United States	Florida Hospital for Children	Orlando	Florida
United States	Oregon Health ans Science University	Portland	Oregon
United States	University of California, San Francisco	San Francisco	California

Sponsors (5)

Lead Sponsor	Collaborator
Cynthia McEvoy	Florida Hospital for Children, Thrasher Research Fund, University of California, San Francisco, University of Florida

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The clinical and anti-inflammatory efficacy of escalating doses of budesonide suspended in calfactant and given into the lungs of ELGANs 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 (see calculation below); 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
Primary	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.	B. AND 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	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
Secondary	Serial Budesonide Levels	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
Secondary	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.	28 days of life for each dosing group
Secondary	Mean Airway Pressure and Oxygen Requirement Correlated to Budesonide levels	The individual patient's decrease in RSS will be correlated with their budesonide exposure measures by the area under the concentration time curve (AUC).	28 days of life for each dosing group