Inhaled Budesonide for Non-ventilated Infants at High Risk of Bronchopulmonary Dysplasia: the i-BUD Pilot Study

Evaluation of the Effectiveness of Inhaled Budesonide for Non-ventilated Infants at High Risk of Bronchopulmonary Dysplasia: the i-BUD Pilot Study

Bronchopulmonary dysplasia (BPD) is one of the most important morbidities of preterm infants with a high incidence and significant impact on resource utilization and long-term outcome. Systemic corticosteroids have been shown to be effective in the prevention of BPD through their potent anti-inflammatory effects but there are serious concerns on their potential detrimental effects on neurodevelopment of infants. In contrast, inhaled corticosteroids administered to ventilated infants are thought to be safer due to their topical effect but have not been shown to improve outcomes including BPD. To date, there have been few studies evaluating the effect of inhaled corticosteroids administered to non-ventilated infants for the prevention of BPD. Hence, we are conducting a double-blind randomized controlled pilot trial to examine the impact of inhaled budesonide on non-ventilated infants.

The study objectives, in a cohort of very preterm infants with signs of early BPD are: 1) to evaluate the effect of aerosolized budesonide on 'days on supplemental oxygen', and 2) to gain an estimate of the impact on BPD and 3) to assess the safety of the intervention in a small cohort of preterm infants.

This will be a single-center randomized double-blind controlled pilot trial. We will recruit a total of 50 infants born at less than 30 weeks gestation who are on continuous positive airway pressure (CPAP) with fraction of inspired oxygen ≥25% on day 14 of life or later. Inhaled budesonide 1mg (intervention group) or normal saline (placebo) will be administered three times a day until the infants do not need CPAP or supplemental oxygen or reach 36+0/7 weeks corrected gestational age. We will evaluate 'days on supplemental oxygen', BPD, re-intubation rates, days on mechanical ventilation and days on CPAP as well as adverse outcomes.

The prevention of BPD would have a significant positive impact on patient quality of life and medical resource utilization and costs. The study hypothesis is that inhaled budesonide on non-ventilated infants with early signs of BPD will reduce the 'days on supplemental oxygen' indicating a positive effect for the prevention of BPD. The result of this pilot study might also justify and support to proceed to a large confirmatory study to evaluate an effect of the intervention on BPD, in which the estimate of the impact on BPD gained in this pilot trial may be used to calculate a sample size.

Study Overview

• Status: Withdrawn
• Conditions: Bronchopulmonary Dysplasia
• Intervention / Treatment: Drug: Inhaled budesonide; Drug: Normal saline

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 weeks to 1 month (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Spontaneous breathing preterm Infants on day 14 to day 42 of age
• Born at < 30 0/7 weeks gestational age
• Requiring FiO2 ≥ 25% on CPAP including biphasic CPAP or high flow nasal canula

Exclusion Criteria:

• Presence of chromosomal defects or major congenital anomalies
• Presence of severe infections including sepsis, meningitis, pneumonia, systemic fungal infections
• History of administration of systemic corticosteroids for pulmonary problems, not including that for hypotension

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Inhaled budesonide; Inhaled budesonide 1mg/dose (2ml) three tid	Drug: Inhaled budesonide; Inhaled budesonide 1 mg tid until 36 weeks' corrected gestational age or fully weaned from supplemental oxygen and respiratory support (CPAP or high flow nasal canula); Other Names: PULMICORT® NEBUAMP®
PLACEBO_COMPARATOR: Normal saline; Normal saline inhalation 2ml tid	Drug: Normal saline; 2 ml normal saline by inhalation; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Total days on supplemental oxygen from birth to discharge	Participants will be followed for the duration of hospital stay, an expected average of 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bronchopulmonary dysplasia	Bronchopulmonary dysplasia is defined as supplemental oxygen use at 36+0/7 weeks corrected gestational age	At 36+0/7 weeks corrected gestational age
Mortality (all causes)		Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
Death or bronchopulmonary dysplasia		Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
Days on supplement oxygen after the study enrollment		Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
Days on continuous positive airway pressure (CPAP)	Support with continuous positive airway pressure, including use of biphasic CPAP and high flow nasal canula (>= 1L/minutes).	Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
Days with significant apneas	Significant apneas with more than 12 episodes requiring stimulation or more than one episode requiring mask-bagging in a six hour period	Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
Culture proven sepsis		Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
Gastrointestinal bleeding		Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
Persistent hyperglycemia	blood glucose > 10mmol/L more than twice in one day	Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
Hypertension	blood pressure ≥ 95th percentile for infant's gestational and postnatal ages	Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
Salivary cortisol level		2 weeks after the study entry and at the first follow up visit at 6 week's corrected age
Postnatal growth	Weight, Head Circumference and Length	at 36 weeks corrected gestational age and at first follow-up visit at 6 weeks' corrected age
Patent ductus arteriosus	PDA diagnosed clinically or by echocardiography	Participants will be followed for the duration of hospital stay, an expected average of 8 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraventricular hemorrhage	Any grade of intraventricular hemorrhage as assessed on cranial ultrasound	Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
Periventricular leukomalacia	Cystic periventricular leukomalacia as assessed by cranial ultrasound	Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
Retinopathy of prematurity	Stage 3 or 4 or surgery as determined from ophthalmological examination	Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
Necrotizing enterocolitis	Bell's stage 2 or higher	Participants will be followed for the duration of hospital stay, an expected average of 8 weeks

Collaborators and Investigators

• Sponsor: Dr. Michael Dunn
• Investigators: Principal Investigator: Michael Dunn, M.D., Staff Neonatologist; Principal Investigator: Tetsuya Isayama, M.D., Clinical Fellow

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): January 1, 2019
• Primary Completion (ANTICIPATED): July 1, 2020
• Study Completion (ANTICIPATED): September 1, 2020

Study Registration Dates

• First Submitted: June 25, 2013
• First Submitted That Met QC Criteria: July 3, 2013
• First Posted (ESTIMATE): July 10, 2013

Study Record Updates

• Last Update Posted (ACTUAL): August 13, 2018
• Last Update Submitted That Met QC Criteria: August 9, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Premature infants; Inhalation; Budesonide
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; 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: 001-2013; CTRL # 165648 (OTHER: Health Canada)

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
• product manufactured in and exported from the U.S.: No