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

NCT01895075 | Withdrawn Phase 2 DMC

• 2 other identifiers: 001-2013CTRL # 165648
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Bronchopulmonary Dysplasia

Keywords

Budesonide; Inhalation; Premature infants

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• Bronchopulmonary dysplasia

  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)

  Participants will be followed for the duration of hospital stay, an expected average of 8 weeks

Other Outcomes (4)

• Intraventricular hemorrhage

  Participants will be followed for the duration of hospital stay, an expected average of 8 weeks

• Periventricular leukomalacia

  Participants will be followed for the duration of hospital stay, an expected average of 8 weeks

• Retinopathy of prematurity

  Participants will be followed for the duration of hospital stay, an expected average of 8 weeks

Study Arms (2)

Inhaled budesonide

EXPERIMENTAL

Inhaled budesonide 1mg/dose (2ml) three tid

Drug: Inhaled budesonide

Normal saline

PLACEBO COMPARATOR

Normal saline inhalation 2ml tid

Drug: Normal saline

Interventions

Inhaled budesonide DRUG

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)

Also known as: PULMICORT® NEBUAMP®

Inhaled budesonide

Normal saline DRUG

2 ml normal saline by inhalation

Also known as: Placebo

Normal saline

Eligibility Criteria

• Age: 14 Days - 42 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dr. Michael Dunn: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

MeSH Terms

Conditions

Bronchopulmonary Dysplasia; Respiratory Aspiration; Premature Birth

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Respiration Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Michael Dunn, M.D.

  Staff Neonatologist

  PRINCIPAL INVESTIGATOR

• Tetsuya Isayama, M.D.

  Clinical Fellow

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Staff neonatologist

Study Record Dates

• First Submitted: June 25, 2013
• First Posted: July 10, 2013
• Study Start: January 1, 2019
• Primary Completion: July 1, 2020
• Study Completion: September 1, 2020
• Last Updated: August 13, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)