Acute Respiratory Distress Syndrome
Conditions
Keywords
Pediatric acute respiratory distress syndrome, PARDS, Budesonide, inhaled steroids
Brief summary
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).
Interventions
DRUGBudesonide
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.
DRUGPlacebo
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.
DEVICENebulizer
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.
Sponsors
National Center for Advancing Translational Sciences (NCATS)
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
30 Days to 18 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Ventilator-free Days (VFD) | Between the time of enrollment and day 28 after enrollment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Oxygen Saturation Index (OSI) | Day one to last day of last day of mechanical ventilation up to 28 days since enrollment | 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. |
| 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 | — |
| 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-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 1 | — |
| Oxygenation Index (OI) | Day one to last day of last day of mechanical ventilation (up to 10 days) | 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. |
| Neutrophil Count | Day 1 | — |
| FEV1 | 90 days since first day of treatment | Forced expiration in 1st second, abnormal (obstructive)\<80% L/second |
| Forced Expiratory Volume at One Second FEV1/FVC | 90 days since first day of treatment | Restrictive disease if \<70% |
| Forced Vital Capacity (FVC) | 90 days since first day of treatment | \<80% restrictive lung disease, L |
| Forced Expiratory Flow FEF 25-75% | 90 days since first day of treatment | Medium size bronchioles, normal 60-130% |
| Respiratory Resistance by Impulse Oscillometry (IOS) | 90 days since first day of treatment | Rrs 3-35 Hz |
| Respiratory Impedance by Impulse Oscillometry (IOS) | 90 days since first day of treatment | Zrs 3-35 Hz |
| Respiratory Reactance by Impulse Oscillometry (IOS) | 90 days since first day of treatment | Xrs 3-35 Hz |
| MMP-9 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test | Day 1 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Budesonide Administered by Nebulizer 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.
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. | 1 |
| Placebo Administered by Nebulizer 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.
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. | 1 |
| Total | 2 |
Baseline characteristics
| Characteristic | Placebo Administered by Nebulizer | Total | Budesonide Administered by Nebulizer |
|---|---|---|---|
| Age, Continuous | 4 months STANDARD_DEVIATION 0 | 5 months STANDARD_DEVIATION 1.4 | 6 months STANDARD_DEVIATION 0 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 1 participants | 2 participants | 1 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 0 / 1 | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
Primary
Number of Ventilator-free Days (VFD)
Time frame: Between the time of enrollment and day 28 after enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Budesonide Administered by Nebulizer | Number of Ventilator-free Days (VFD) | 20 days |
| Placebo Administered by Nebulizer | Number of Ventilator-free Days (VFD) | 17 days |
Secondary
FEV1
Forced expiration in 1st second, abnormal (obstructive)\<80% L/second
Time frame: 90 days since first day of treatment
Population: Data for this outcome measure were not collected for any participant.
Secondary
Forced Expiratory Flow FEF 25-75%
Medium size bronchioles, normal 60-130%
Time frame: 90 days since first day of treatment
Population: Data for this outcome measure were not collected for any participant.
Secondary
Forced Expiratory Volume at One Second FEV1/FVC
Restrictive disease if \<70%
Time frame: 90 days since first day of treatment
Population: Data for this outcome measure were not collected for any participant.
Secondary
Forced Vital Capacity (FVC)
\<80% restrictive lung disease, L
Time frame: 90 days since first day of treatment
Population: Data for this outcome measure were not collected for any participant.
Secondary
IL-6 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test
Time frame: last day of treatment or last day of invasive mechanical ventilation( upto day 28)
Population: Data for this outcome measure were not collected for any participant.
Secondary
IL-6 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test
Time frame: Day 3
Population: Data for this outcome measure were not collected for any participant.
Secondary
IL-8 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test
Time frame: Day 3
Population: Data for this outcome measure were not collected for any participant.
Secondary
IL-8 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test
Time frame: Day 1
Population: Data for this outcome measure were not collected for any participant.
Secondary
IL-8 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test
Time frame: last day of treatment or last day of invasive mechanical ventilation( upto day 28)
Population: Data for this outcome measure were not collected for any participant.
Secondary
Interleukin (IL) -6 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test
Time frame: Day 1
Population: Data for this outcome measure were not collected for any participant.
Secondary
MMP-8 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test
Time frame: Day 3
Population: Data for this outcome measure were not collected for any participant.
Secondary
MMP-8 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test
Time frame: Day 1
Population: Data for this outcome measure were not collected for any participant.
Secondary
MMP-8 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test
Time frame: last day of treatment or last day of invasive mechanical ventilation( upto day 28)
Population: Data for this outcome measure were not collected for any participant.
Secondary
MMP-9 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test
Time frame: Day 1
Population: Data for this outcome measure were not collected for any participant.
Secondary
MMP-9 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test
Time frame: Day 3
Population: Data for this outcome measure were not collected for any participant.
Secondary
MMP-9 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test
Time frame: last day of treatment or last day of invasive mechanical ventilation( upto day 28)
Population: Data for this outcome measure were not collected for any participant.
Secondary
Neutrophil Count
Time frame: Day 1
Population: Data for this outcome measure were not collected for any participant.
Secondary
Neutrophil Count
Time frame: last day of treatment or last day of invasive mechanical ventilation( upto day 28)
Population: Data for this outcome measure were not collected for any participant.
Secondary
Neutrophil Count
Time frame: Day 3
Population: Data for this outcome measure were not collected for any participant.
Secondary
Number of Days Participant Stayed in Hospital
Time frame: from time of enrollment until participant is transferred, discharged, or deceased (up to 50 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Budesonide Administered by Nebulizer | Number of Days Participant Stayed in Hospital | 46 days |
| Placebo Administered by Nebulizer | Number of Days Participant Stayed in Hospital | 23 days |
Secondary
Number of Days Participant Stayed in Pediatric Intensive Care Unit (PICU)
Time frame: from time of enrollment until participant is transferred, discharged, or deceased (up to 50 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Budesonide Administered by Nebulizer | Number of Days Participant Stayed in Pediatric Intensive Care Unit (PICU) | 46 days |
| Placebo Administered by Nebulizer | Number of Days Participant Stayed in Pediatric Intensive Care Unit (PICU) | 17 days |
Secondary
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.
Time frame: Day one to last day of last day of mechanical ventilation (up to 10 days)
Population: For the participant in the budesonide arm, data for this outcome measure was not collected on days 9 and 10.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Budesonide Administered by Nebulizer | Oxygenation Index (OI) | day 8 | 2.8 index | Standard Deviation 0 |
| Budesonide Administered by Nebulizer | Oxygenation Index (OI) | day 2 | 11 index | Standard Deviation 0 |
| Budesonide Administered by Nebulizer | Oxygenation Index (OI) | day 1 | 11 index | Standard Deviation 0 |
| Budesonide Administered by Nebulizer | Oxygenation Index (OI) | day 3 | 8 index | Standard Deviation 0 |
| Budesonide Administered by Nebulizer | Oxygenation Index (OI) | day 4 | 4 index | Standard Deviation 0 |
| Budesonide Administered by Nebulizer | Oxygenation Index (OI) | day 5 | 3.2 index | Standard Deviation 0 |
| Budesonide Administered by Nebulizer | Oxygenation Index (OI) | day 6 | 3.5 index | Standard Deviation 0 |
| Budesonide Administered by Nebulizer | Oxygenation Index (OI) | day 7 | 5 index | Standard Deviation 0 |
| Placebo Administered by Nebulizer | Oxygenation Index (OI) | day 3 | 11.4 index | Standard Deviation 0 |
| Placebo Administered by Nebulizer | Oxygenation Index (OI) | day 6 | 11.5 index | Standard Deviation 0 |
| Placebo Administered by Nebulizer | Oxygenation Index (OI) | day 4 | 6.4 index | Standard Deviation 0 |
| Placebo Administered by Nebulizer | Oxygenation Index (OI) | day 10 | 5 index | Standard Deviation 0 |
| Placebo Administered by Nebulizer | Oxygenation Index (OI) | day 8 | 8.7 index | Standard Deviation 0 |
| Placebo Administered by Nebulizer | Oxygenation Index (OI) | day 9 | 5 index | Standard Deviation 0 |
| Placebo Administered by Nebulizer | Oxygenation Index (OI) | day 5 | 14.4 index | Standard Deviation 0 |
| Placebo Administered by Nebulizer | Oxygenation Index (OI) | day 1 | 12 index | Standard Deviation 0 |
| Placebo Administered by Nebulizer | Oxygenation Index (OI) | day 2 | 8 index | Standard Deviation 0 |
| Placebo Administered by Nebulizer | Oxygenation Index (OI) | day 7 | 10 index | Standard Deviation 0 |
Secondary
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.
Time frame: Day one to last day of last day of mechanical ventilation up to 28 days since enrollment
Population: Data for this outcome measure were not collected for either participant.
Secondary
Respiratory Impedance by Impulse Oscillometry (IOS)
Zrs 3-35 Hz
Time frame: 90 days since first day of treatment
Population: Data for this outcome measure were not collected for any participant.
Secondary
Respiratory Reactance by Impulse Oscillometry (IOS)
Xrs 3-35 Hz
Time frame: 90 days since first day of treatment
Population: Data for this outcome measure were not collected for any participant.
Secondary
Respiratory Resistance by Impulse Oscillometry (IOS)
Rrs 3-35 Hz
Time frame: 90 days since first day of treatment
Population: Data for this outcome measure were not collected for any participant.
Secondary
TNF Alpha Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test
Time frame: Day 1
Population: Data for this outcome measure were not collected for any participant.
Secondary
TNF Alpha Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test
Time frame: last day of treatment or last day of invasive mechanical ventilation( upto day 28)
Population: Data for this outcome measure were not collected for any participant.
Secondary
TNF Alpha Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test
Time frame: Day 3
Population: Data for this outcome measure were not collected for any participant.