Asthma Childhood
Conditions
Brief summary
Determine if differences in (1) pediatric intensive care unit length of stay, (2) continuous nebulized albuterol duration, and (3) a composite outcome of advanced asthma therapy incidence including use of non-invasive ventilation (NIV), terbutaline, inhaled helium and mechanical ventilation between cohorts of children admitted with status asthmaticus to the PICU treated with either IV dexamethasone (DM) or methylprednisolone (MP).
Detailed description
As the pathophysiology of an acute asthma exacerbation is dysregulated inflammatory pathways, standard treatment includes the prompt initiation of intravenous systemic corticosteroids. Corticosteroids reduce the production of many mediators involved in the inflammatory process and inhibit macrophages, monocytes, T-lymphocytes, eosinophils, and basophils, which are activated during this process. Furthermore, corticosteroids improve the efficacy of beta-2 agonists, such as albuterol, a nebulized medication used for bronchodilation in acute asthma exacerbations. There remains an ongoing dialogue among the expert medical community regarding the superiority of specific IV corticosteroid, dosing, route and delivery. This debate continues secondary to a lack of definitive comparative data in the literature. While the benefits of receiving systemic corticosteroids has been demonstrated in multiple studies, to date, no head-to-head trials have been conducted comparing IV systemic corticosteroids in the PICU setting (DM vs. MP). While several systemic corticosteroids are FDA approved for the treatment of asthma exacerbation including prednisone, prednisolone, MP and DM, the standard practice in PICU-level care is IV MP every 6 hours until enteral medications can be safely tolerated. Recent data from emergency room literature would suggest there is equipoise in use of dexamethasone as an alternative for methylprednisolone due to its increased glucocorticoid (anti-inflammatory) potency. Steroid agents are chosen at the discretion of clinical providers based upon a child's capacity to tolerate enteral medications and the specific clinical setting (outpatient vs. general inpatient vs. critical inpatient). The investigators have performed a retrospective study over a 2-year period to assess if differences in clinical outcomes or adverse events exist in cohorts defined by DM exposure in the ER. Their data revealed no differences, but most children were switched to MP during their PICU stay making data analyses severely confounded by exposure to the defining characteristics of the comparative cohort. The investigators seek to first prospectively consent individuals to receive DM during their PICU asthma treatment and compare outcomes to PICU asthmatics concurrently admitted to the PICU receiving local standard care (MP). Johns Hopkins All Children's Hospital (JHACH) admits approximately 150 asthmatics per year in the PICU and the investigators hope to enroll up to 50 subjects into a DM only arm. The comparative standard care arm will be assessed at the end of the study period. Primary outcomes include (1) PICU Length of Stay, (2) Continuous nebulized albuterol duration, and (3) a composite outcome including use of non-invasive ventilation (NIV), terbutaline, inhaled helium, inhaled anesthetic gas, mechanical ventilation, and extracorporeal life support. This research will provide the needed epidemiologic and basic comparative data required to power and conduct a definitive, head-to-head trial of DM vs. MP.
Interventions
Non-randomized, open-label, prospective use of intravenous dexamethasone for children admitted to the PICU with status asthmaticus
Sponsors
Study design
Intervention model description
Single Arm Treatment Group with a Prospective, Comparative Cohort Receiving Standard Care
Eligibility
Inclusion criteria
* Inclusion criteria are children 5 to 17 years of age with primary admission diagnoses of acute asthma exacerbation or status asthmaticus admitted to the PICU
Exclusion criteria
* children with existing tracheostomy, cystic fibrosis, and pulmonary hypertension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Length of Stay | From enrollment through hospital discharge, up to 1 week | Hospital length of stay measured in days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Continuous Nebulized Albuterol | From enrollment through hospital discharge, up to 1 week | Duration (in days) of continuous nebulized albuterol. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Receiving an Adjunctive Asthma Therapy | From enrollment through hospital discharge, up to 1 week | Number of participants receiving an adjunctive therapy: * use of non-invasive ventilation (NIV) * terbutaline * inhaled helium * inhaled anesthetic gas * mechanical ventilation * extracorporeal life support |
| Corticosteroid-related Adverse Events | From enrollment through hospital discharge, up to 1 week | Rates of known corticosteroid-related adverse events including clinically-relevant gastrointestinal bleeding, gastritis, ventilator associated pneumonia, necrotizing enterocolitis, hypertension, hyperglycemia, altered mentation (including hallucinations and delirium), and adrenal insufficiency observed prior to hospital discharge. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Methylprednisolone Arm - Standard Care Non-randomized, prospective, observational arm of children receiving standard care for status asthmaticus in the PICU with intravenous methylprednisolone. | 61 |
| Dexamethasone Arm - Interventional Arm Non-randomized, open-label, prospective use of intravenous dexamethasone for children admitted to the PICU with status asthmaticus.
Dexamethasone: Non-randomized, open-label, prospective use of intravenous dexamethasone for children admitted to the PICU with status asthmaticus | 31 |
| Total | 92 |
Baseline characteristics
| Characteristic | Methylprednisolone Arm - Standard Care | Dexamethasone Arm - Interventional Arm | Total |
|---|---|---|---|
| Age, Continuous | 9.7 years STANDARD_DEVIATION 3.8 | 9.3 years STANDARD_DEVIATION 3.5 | 9.6 years STANDARD_DEVIATION 3.8 |
| NHLBI Asthma Classification Intermittent | 10 Participants | 4 Participants | 14 Participants |
| NHLBI Asthma Classification Mild Persistent | 13 Participants | 7 Participants | 20 Participants |
| NHLBI Asthma Classification Moderate Persistent | 26 Participants | 10 Participants | 36 Participants |
| NHLBI Asthma Classification Severe Persistent | 12 Participants | 10 Participants | 22 Participants |
| Pediatric Asthma Severity Score | 11 units on a scale | 10.5 units on a scale | 11 units on a scale |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 30 Participants | 13 Participants | 43 Participants |
| Sex: Female, Male Male | 31 Participants | 18 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 61 | 0 / 31 |
| other Total, other adverse events | 12 / 61 | 3 / 31 |
| serious Total, serious adverse events | 0 / 61 | 0 / 31 |
Outcome results
Length of Stay
Hospital length of stay measured in days.
Time frame: From enrollment through hospital discharge, up to 1 week
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Methylprednisolone Arm - Standard Care | Length of Stay | 2.9 days |
| Dexamethasone Arm - Interventional Arm | Length of Stay | 2.9 days |
Duration of Continuous Nebulized Albuterol
Duration (in days) of continuous nebulized albuterol.
Time frame: From enrollment through hospital discharge, up to 1 week
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Methylprednisolone Arm - Standard Care | Duration of Continuous Nebulized Albuterol | 1 days |
| Dexamethasone Arm - Interventional Arm | Duration of Continuous Nebulized Albuterol | 0.8 days |
Corticosteroid-related Adverse Events
Rates of known corticosteroid-related adverse events including clinically-relevant gastrointestinal bleeding, gastritis, ventilator associated pneumonia, necrotizing enterocolitis, hypertension, hyperglycemia, altered mentation (including hallucinations and delirium), and adrenal insufficiency observed prior to hospital discharge.
Time frame: From enrollment through hospital discharge, up to 1 week
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Methylprednisolone Arm - Standard Care | Corticosteroid-related Adverse Events | Hyperglycemia | 7 Participants |
| Methylprednisolone Arm - Standard Care | Corticosteroid-related Adverse Events | Gastritis | 0 Participants |
| Methylprednisolone Arm - Standard Care | Corticosteroid-related Adverse Events | Hypertension | 1 Participants |
| Methylprednisolone Arm - Standard Care | Corticosteroid-related Adverse Events | Adrenal insufficiency | 2 Participants |
| Methylprednisolone Arm - Standard Care | Corticosteroid-related Adverse Events | Altered mentation | 2 Participants |
| Methylprednisolone Arm - Standard Care | Corticosteroid-related Adverse Events | Clinically-relevant gastrointestinal bleeding | 0 Participants |
| Methylprednisolone Arm - Standard Care | Corticosteroid-related Adverse Events | Necrotizing enterocolitis | 0 Participants |
| Methylprednisolone Arm - Standard Care | Corticosteroid-related Adverse Events | Ventilator associated pneumonia | 0 Participants |
| Dexamethasone Arm - Interventional Arm | Corticosteroid-related Adverse Events | Ventilator associated pneumonia | 0 Participants |
| Dexamethasone Arm - Interventional Arm | Corticosteroid-related Adverse Events | Clinically-relevant gastrointestinal bleeding | 0 Participants |
| Dexamethasone Arm - Interventional Arm | Corticosteroid-related Adverse Events | Altered mentation | 0 Participants |
| Dexamethasone Arm - Interventional Arm | Corticosteroid-related Adverse Events | Hyperglycemia | 2 Participants |
| Dexamethasone Arm - Interventional Arm | Corticosteroid-related Adverse Events | Necrotizing enterocolitis | 0 Participants |
| Dexamethasone Arm - Interventional Arm | Corticosteroid-related Adverse Events | Hypertension | 1 Participants |
| Dexamethasone Arm - Interventional Arm | Corticosteroid-related Adverse Events | Gastritis | 0 Participants |
| Dexamethasone Arm - Interventional Arm | Corticosteroid-related Adverse Events | Adrenal insufficiency | 0 Participants |
Number of Participants Receiving an Adjunctive Asthma Therapy
Number of participants receiving an adjunctive therapy: * use of non-invasive ventilation (NIV) * terbutaline * inhaled helium * inhaled anesthetic gas * mechanical ventilation * extracorporeal life support
Time frame: From enrollment through hospital discharge, up to 1 week
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Methylprednisolone Arm - Standard Care | Number of Participants Receiving an Adjunctive Asthma Therapy | 41 Participants |
| Dexamethasone Arm - Interventional Arm | Number of Participants Receiving an Adjunctive Asthma Therapy | 16 Participants |