Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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).
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Methylprednisolone Arm | No Intervention | Non-randomized, prospective, observational arm of children receiving standard care for status asthmaticus in the PICU with intravenous methylprednisolone. | |
| Dexamethasone Arm | Experimental | Non-randomized, open-label, prospective use of intravenous dexamethasone for children admitted to the PICU with status asthmaticus. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dexamethasone | Drug | Non-randomized, open-label, prospective use of intravenous dexamethasone for children admitted to the PICU with status asthmaticus |
|
| Measure | Description | Time Frame |
|---|---|---|
| Length of Stay | Hospital length of stay measured in days. | From enrollment through hospital discharge, up to 1 week |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of Continuous Nebulized Albuterol | Duration (in days) of continuous nebulized albuterol. | From enrollment through hospital discharge, up to 1 week |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Receiving an Adjunctive Asthma Therapy | Number of participants receiving an adjunctive therapy:
| From enrollment through hospital discharge, up to 1 week |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Anthony A Sochet, MD, MS | Johns Hopkins All Children's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins All Children's Hospital | St. Petersburg | Florida | 33701 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 9728226 | Background | Taylor IK, Shaw RJ. The mechanism of action of corticosteroids in asthma. Respir Med. 1993 May;87(4):261-77. doi: 10.1016/0954-6111(93)90022-r. No abstract available. | |
| 1968733 | Background | Svedmyr N. Action of corticosteroids on beta-adrenergic receptors. Clinical aspects. Am Rev Respir Dis. 1990 Feb;141(2 Pt 2):S31-8. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Methylprednisolone Arm - Standard Care | Non-randomized, prospective, observational arm of children receiving standard care for status asthmaticus in the PICU with intravenous methylprednisolone 0.5mg/kg/dose every 6-hours for 5-days. |
| FG001 | Dexamethasone Arm - Interventional Arm | Non-randomized, open-label, prospective use of intravenous dexamethasone 0.25 mg/kg/dose every 6 hours for 2-days 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Methylprednisolone Arm - Standard Care | Non-randomized, prospective, observational arm of children receiving standard care for status asthmaticus in the PICU with intravenous methylprednisolone. |
| BG001 | Dexamethasone Arm - Interventional Arm |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Length of Stay | Hospital length of stay measured in days. | Posted | Mean | Inter-Quartile Range | days | From enrollment through hospital discharge, up to 1 week |
|
From enrollment to hospital discharge or 30-days; whichever comes first.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Methylprednisolone Arm - Standard Care | Non-randomized, prospective, observational arm of children receiving standard care for status asthmaticus in the PICU with intravenous methylprednisolone. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyperglycemia | Endocrine disorders | Non-systematic Assessment | Steroid induced hyperglycemia |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Anthony Sochet | Johns Hopkins All Children's Hospital | 7277672912 | Anthony.Sochet@jhmi.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 28, 2019 | May 15, 2022 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D003907 | Dexamethasone |
| ID | Term |
|---|---|
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
Not provided
Not provided
Single Arm Treatment Group with a Prospective, Comparative Cohort Receiving Standard Care
Not provided
Not provided
Not provided
Not provided
| 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. |
| From enrollment through hospital discharge, up to 1 week |
| 8414819 | Background | Scarfone RJ, Fuchs SM, Nager AL, Shane SA. Controlled trial of oral prednisone in the emergency department treatment of children with acute asthma. Pediatrics. 1993 Oct;92(4):513-8. |
| 8135557 | Background | Connett GJ, Warde C, Wooler E, Lenney W. Prednisolone and salbutamol in the hospital treatment of acute asthma. Arch Dis Child. 1994 Mar;70(3):170-3. doi: 10.1136/adc.70.3.170. |
| 2882288 | Background | Storr J, Barrell E, Barry W, Lenney W, Hatcher G. Effect of a single oral dose of prednisolone in acute childhood asthma. Lancet. 1987 Apr 18;1(8538):879-82. doi: 10.1016/s0140-6736(87)92857-1. |
| 2267922 | Background | Gleeson JG, Loftus BG, Price JF. Placebo controlled trial of systemic corticosteroids in acute childhood asthma. Acta Paediatr Scand. 1990 Nov;79(11):1052-8. doi: 10.1111/j.1651-2227.1990.tb11382.x. |
| 7359263 | Background | Kattan M, Gurwitz D, Levison H. Corticosteroids in status asthmaticus. J Pediatr. 1980 Mar;96(3 Pt 2):596-9. doi: 10.1016/s0022-3476(80)80872-9. |
| 24515516 | Background | Keeney GE, Gray MP, Morrison AK, Levas MN, Kessler EA, Hill GD, Gorelick MH, Jackson JL. Dexamethasone for acute asthma exacerbations in children: a meta-analysis. Pediatrics. 2014 Mar;133(3):493-9. doi: 10.1542/peds.2013-2273. Epub 2014 Feb 10. |
| 29173304 | Background | Paniagua N, Lopez R, Munoz N, Tames M, Mojica E, Arana-Arri E, Mintegi S, Benito J. Randomized Trial of Dexamethasone Versus Prednisone for Children with Acute Asthma Exacerbations. J Pediatr. 2017 Dec;191:190-196.e1. doi: 10.1016/j.jpeds.2017.08.030. |
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 |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| NHLBI Asthma Classification | National Heart Lung and Blood Institute Chronic Asthma Severity Classification | Count of Participants | Participants |
|
| Pediatric Asthma Severity Score | Score ranges from 5-15. Greater scores signify greater severity of illness with respect to asthma exacerbation. | Median | Inter-Quartile Range | units on a scale |
|
|
|
|
| Secondary | Duration of Continuous Nebulized Albuterol | Duration (in days) of continuous nebulized albuterol. | Posted | Median | Inter-Quartile Range | days | From enrollment through hospital discharge, up to 1 week |
|
|
|
|
| Other Pre-specified | Number of Participants Receiving an Adjunctive Asthma Therapy | Number of participants receiving an adjunctive therapy:
| Posted | Count of Participants | Participants | From enrollment through hospital discharge, up to 1 week |
|
|
|
|
| Other Pre-specified | 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. | Posted | Count of Participants | Participants | From enrollment through hospital discharge, up to 1 week |
|
|
|
| 0 |
| 61 |
| 0 |
| 61 |
| 12 |
| 61 |
| EG001 | 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 | 0 | 31 | 0 | 31 | 3 | 31 |
|
| Hypertension | General disorders | Non-systematic Assessment |
|
| Adrenal Insufficiency | Endocrine disorders | Non-systematic Assessment |
|
| Altered Mentation | Nervous system disorders | Non-systematic Assessment |
|
Not provided
Not provided
| D000072473 |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
| Moderate Persistent |
|
| Severe Persistent |
|
| Adrenal insufficiency |
|
| Altered mentation |
|
| Clinically-relevant gastrointestinal bleeding |
|
| Gastritis |
|
| Necrotizing enterocolitis |
|
| Ventilator associated pneumonia |
|