Ideal Steroids for Asthma Treatment in the PICU

Asthma Childhood Clinical Trial

— iSTAT PICU  

Official title:

Ideal Steroids for Asthma Treatment in the PICU (iSTAT PICU): A Prospective, Comparative, Single-arm Study Assessing Dexamethasone Versus Methylprednisolone in Severe Status Asthmaticus Admitted to the Pediatric Intensive Care Unit

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03900624
• Other study ID #: IRB00187813
• Status: Completed
• Phase: Phase 4
• Start date: April 21, 2019
• Est. completion date: May 15, 2022

Study information

• Verified date: February 2024
• Source: Johns Hopkins All Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: May 15, 2022
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 17 Years

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

Related Conditions & MeSH terms

• Asthma
• Asthma Childhood

Intervention

Drug:
• Dexamethasone
Non-randomized, open-label, prospective use of intravenous dexamethasone for children admitted to the PICU with status asthmaticus

Locations

Country	Name	City	State
United States	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Johns Hopkins All Children's Hospital

Country where clinical trial is conducted

United States, 

References & Publications (9)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Svedmyr N. Action of corticosteroids on beta-adrenergic receptors. Clinical aspects. Am Rev Respir Dis. 1990 Feb;141(2 Pt 2):S31-8. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	From enrollment through hospital discharge, up to 1 week
Other	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
Primary	Length of Stay	Hospital length of stay measured in days.	From enrollment through hospital discharge, up to 1 week
Secondary	Duration of Continuous Nebulized Albuterol	Duration (in days) of continuous nebulized albuterol.	From enrollment through hospital discharge, up to 1 week