Inhaled Steroids for the Treatment of Early Pediatric Acute Respiratory Distress Syndrome

Inhaled Steroids for the Treatment of Early Pediatric Acute Respiratory Distress Syndrome (PARDS), a Randomized Pilot Trial

The purpose of this study is to show that inhaled steroids in patient with PARDS can decrease the days on mechanical ventilator measured by ventilator-free days,to improve the oxygenation index (OI) or oxygenation saturation index (OSI) in patients receiving inhaled steroids and to show the relevance and feasibility of a larger study by assessing the hypothesis in a small cohort of patients. Patient will be treated for a maximum of 10 days. Secondary objectives are to reduce the length of stay (LOS) in the pediatric intensive care unit (PICU) and hospital admissions; to show less inflammation in the patients receiving inhaled steroids by measuring inflammatory markers from tracheal aspirates like Interleukin (IL6, IL8, tumor necrosis factor (TNF) α, matrix metalloproteinase8 (MMP8) and matrix metalloproteinase9 (MMP9). Lastly, to show that inhaled steroids can improve residual lung disease evaluated by Pulmonary Function Test (PFTs) and Impulse Oscillometry (IOS).

Study Overview

• Status: Terminated
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: Budesonide; Device: Nebulizer; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pediatric patients older than 30 days and up to 18 years of age admitted to the PICU with a diagnosis of PARDS enrolled within 72 hours of diagnosis.
• Patients requiring invasive mechanical ventilation.
• Criteria of PARDS as defined by the Pediatric Acute Lung Injury Consensus Conference (PALICC), on June 2015 in Pediatric Critical Care Journal

Exclusion Criteria:

• Patients with diffuse alveolar hemorrhage.
• Patients terminally ill with limitation of care or in hospice care.
• Patients receiving inhaled steroids or systemic steroids as chronic therapy before admission.
• Patients with high dose systemic steroids for anti-inflammatory purposes. The investigators will not exclude patients receiving hydrocortisone for shock.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Budesonide administered by nebulizer	Drug: Budesonide; Enrolled patients will be treated with Pulmicort Respules® (Budesonide inhalation suspension), at a dose of 0.5 mg, nebulized twice daily through the mechanical ventilator. The medication will be administered to the patient by the respiratory therapist with the single-patient-use medication nebulizer attached to the mechanical ventilator circuit. The maximum length of treatment will be 10 days.; Other Names: Pulmicort Respules®; Device: Nebulizer; The medication will be administered to the patient by the respiratory therapist with the single-patient-use medication nebulizer attached to the mechanical ventilator circuit.
Placebo Comparator: Placebo administered by nebulizer	Device: Nebulizer; The medication will be administered to the patient by the respiratory therapist with the single-patient-use medication nebulizer attached to the mechanical ventilator circuit.; Drug: Placebo; Enrolled patients will be treated with normal saline.The medication will be administered to the patient by the respiratory therapist with the single-patient-use medication nebulizer attached to the mechanical ventilator circuit. The maximum length of treatment will be 10 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Ventilator-free Days (VFD)	Between the time of enrollment and day 28 after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxygenation Index (OI)	Oxygenation index (OI) is calculated as ([FiO2 x Mean Airway Pressure] / PaO2). FiO2 stands for inspired fraction of oxygen, and PaO2 stands for pressure/arterial pressure of oxygen. An oxygenation index of 4-8 indicates mild ARDS, an oxygenation index of 8-16 indicates moderate ARDS, and an oxygenation index greater than 16 indicates severe ARDS.	Day one to last day of last day of mechanical ventilation (up to 10 days)
Oxygen Saturation Index (OSI)	5-7.5 mild ARDS, 7.5-12.3 moderate ARDS. > 12.3 severe ARDS, formula FiO2*Mean airway pressure/Saturation of O2 Oxygen saturation index (OI) is calculated as ([FiO2 x Mean Airway Pressure] / Saturation of oxygen). FiO2 stands for inspired fraction of oxygen. An oxygen saturation index of 5-7.5 indicates mild ARDS, an oxygen saturation index of 7.5-12.3 indicates moderate ARDS, and an oxygen saturation index greater than 12.3 indicates severe ARDS.	Day one to last day of last day of mechanical ventilation up to 28 days since enrollment
Number of Days Participant Stayed in Pediatric Intensive Care Unit (PICU)		from time of enrollment until participant is transferred, discharged, or deceased (up to 50 days)
Number of Days Participant Stayed in Hospital		from time of enrollment until participant is transferred, discharged, or deceased (up to 50 days)
TNF Alpha Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test		Day 1
TNF Alpha Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test		Day 3
TNF Alpha Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test		last day of treatment or last day of invasive mechanical ventilation( upto day 28)
Interleukin (IL) -6 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test		Day 1
IL-6 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test		Day 3
IL-6 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test		last day of treatment or last day of invasive mechanical ventilation( upto day 28)
IL-8 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test		Day 1
IL-8 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test		Day 3
IL-8 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test		last day of treatment or last day of invasive mechanical ventilation( upto day 28)
MMP-8 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test		Day 1
MMP-8 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test		Day 3
MMP-8 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test		last day of treatment or last day of invasive mechanical ventilation( upto day 28)
MMP-9 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test		Day 1
MMP-9 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test		Day 3
MMP-9 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test		last day of treatment or last day of invasive mechanical ventilation( upto day 28)
Neutrophil Count		Day 1
Neutrophil Count		Day 3
Neutrophil Count		last day of treatment or last day of invasive mechanical ventilation( upto day 28)
FEV1	Forced expiration in 1st second, abnormal (obstructive)<80% L/second	90 days since first day of treatment
Forced Expiratory Volume at One Second FEV1/FVC	Restrictive disease if <70%	90 days since first day of treatment
Forced Vital Capacity (FVC)	<80% restrictive lung disease, L	90 days since first day of treatment
Forced Expiratory Flow FEF 25-75%	Medium size bronchioles, normal 60-130%	90 days since first day of treatment
Respiratory Resistance by Impulse Oscillometry (IOS)	Rrs 3-35 Hz	90 days since first day of treatment
Respiratory Impedance by Impulse Oscillometry (IOS)	Zrs 3-35 Hz	90 days since first day of treatment
Respiratory Reactance by Impulse Oscillometry (IOS)	Xrs 3-35 Hz	90 days since first day of treatment

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Alvaro J Coronado Munoz, MD, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2020
• Primary Completion (Actual): March 30, 2020
• Study Completion (Actual): March 30, 2020

Study Registration Dates

• First Submitted: August 16, 2019
• First Submitted That Met QC Criteria: August 19, 2019
• First Posted (Actual): August 22, 2019

Study Record Updates

• Last Update Posted (Actual): July 13, 2022
• Last Update Submitted That Met QC Criteria: June 24, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Budesonide; inhaled steroids; Pediatric acute respiratory distress syndrome; PARDS
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; 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: HSC-MS-19-0566; KL2TR003168 (U.S. NIH Grant/Contract)

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No