Intratracheal Budesonide/Surfactant Prevents BPD

Routine Administration of Surfactant/Budesonide to Prevent BPD in VLBW With RDS-A Double Blind Study

A double-blind study includes: 1) birth Wt 500-1499 gm, 2) respiratory distress shortly after birth and requires resuscitation 3) failure to NCPAP within 4 hrs after birth, defined as: a) FIO2 ≥ 0.30, pressure > 5cmH2O b) severe retraction c) apnea d) PCO2 ≥ 60 mmHg. Exclusion criteria: 1) lethal cardiopulmonary status 2) severe congenital anomalies.

Given the COVID19 pandemics, the recruitment became difficult. Under the consideration of scientific and practical consideration, we therefore determine to have a sample of 300, (150 in each group), fulfill the criteria of type I error 0.05, type II error 0.10, power 90% and with an expectation of 30 % improvement of primary outcome (from 60 % in control group to 40 % in the intervention group as original presumed).Appropriate amount of placebo will be used as it does not affect the biophysical property of curosurf (PAS abstract 2017 San Francisco). Primary outcome of study is death or BPD defined by NICHD criteria. Follow up study of neuromotor and cognitive function and pulmonary states will be done at 1-2 years of corrected age.

Study Overview

• Status: Completed
• Conditions: Respiratory Distress Syndrome; Bronchopulmonary Dysplasia
• Intervention / Treatment: Drug: budesonide; Drug: Saline

Detailed Description

A double-blind study will be conducted in 7 tertiary centers. Inclusion criteria are: 1) birth Wt 500-1499 gm, 2) respiratory distress shortly after birth and requires resuscitation 3) failure to NCPAP within 4 hrs after birth, defined as: a) FIO2 ≥ 0.30, pressure > 5cmH2O b) severe retraction c) apnea d) PCO2 ≥ 60 mmHg. Exclusion criteria: 1) lethal cardiopulmonary status 2) severe congenital anomalies.

The initial sample size was determined based on the expectation of 30% improvement of the primary outcome (BPD/death) in the intervention group (Curosurf + budesonide) (40%), as compared to control group (Curosurf +saline placebo) (60%), specifying a type I error of 0.05 and type II error 0.20. The total number needed was 240 (120 in each group). The study was started in June 2019 before the pandemic of COVID19 and the study went on smoothly in 2019. Because of the smooth enrollment of the patients in 2019, we decided to increase the ability of the study for detecting the intervention effect through increasing the power from 80 % to 90 % (type II error from 0.2 to 0.1 and type I error decreased from 0.05 to 0.02). The total sample size required was estimated to be 350 (170 in each group). Given the COVID19 pandemics, the recruitment became difficult. Under the consideration of scientific and practical consideration, we therefore determine to have a sample of 300, (150 in each group), fulfill the criteria of type I error 0.05, type II error 0.10, power 90% and with an expectation of 30 % improvement of primary outcome (from 60 % in control group to 40 % in the intervention group as original presumed). The changes in sample size had been approved by independent monitoring committee. We expect that the study will be completed in September 2022.

The sample will be stratified based on birth weight (500-749 grams, 750-999 grams and 1000-1499 grams), the presence of clinical chorioamnionitis or not, and site of study.

• Study Type: Interventional
• Enrollment (Actual): 310
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 minutes to 4 hours (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1) birth Wt 500-1499 gm, 2) respiratory distress shortly after birth and requires resuscitation, 3) failure to NCPAP within 4 hrs after birth, defined as: a) FIO2 ≥ 0.30, pressure > 5 cmH2O b) severe retraction c) apnea d) PCO2 ≥ 60 mmHg.

Exclusion Criteria:

• 1) lethal cardiopulmonary status, 2) severe congenital anomalies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Experimental; Curosurf + budesonide	Drug: budesonide; Intra-tracheal instillation of a combination of budesonide/surfactant in preterm infants with RDS to prevent BPD; Other Names: pulmicort
Placebo Comparator: Placebo; Curosurf + saline	Drug: Saline; Intra-tracheal instillation of a combination of saline/surfactant in preterm infants with RDS to prevent BPD; Other Names: sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of death or BPD	Primary outcome of study is death or BPD defined by NICHD criteria.	6 months

Collaborators and Investigators

• Sponsor: Taipei Medical University
• Collaborators: National Taiwan University Hospital; Mackay Memorial Hospital; China Medical University Hospital; Chang Gung Memorial Hospital; Taipei Veterans General Hospital, Taiwan; Taipei Medical University Hospital; Seventh Medical Center of PLA General Hospital; Taichung Veterans General Hospital; Guangzhou Women and Children's Medical Center
• Investigators: Principal Investigator: Tsu F Yeh, M.D., Ph.D., Maternal Child Health Research Center, Taipei Medical 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.
• Kuo HT, Lin HC, Tsai CH, Chouc IC, Yeh TF. A follow-up study of preterm infants given budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants. J Pediatr. 2010 Apr;156(4):537-41. doi: 10.1016/j.jpeds.2009.10.049. Epub 2010 Feb 6.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: September 5, 2017
• First Submitted That Met QC Criteria: September 6, 2017
• First Posted (Actual): September 7, 2017

Study Record Updates

• Last Update Posted (Actual): May 30, 2023
• Last Update Submitted That Met QC Criteria: May 25, 2023
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: BPD; budesonide; respiratory distress syndrome; surfactant
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Bronchopulmonary Dysplasia; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Budesonide
• Other Study ID Numbers: N201705026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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