Pediatric Asthma Trial of Corticosteroid Heterogeneity (PATCH): A Phase 2 Prospective Randomized Open Blinded End-point (PROBE) Design, Randomized Clinical Trial of Dexamethasone Versus Methylprednisolone for Pediatric Critical Asthma
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Enrollment
- 159
- Locations
- 1
- Primary Endpoint
- Post-Discharge Systemic Corticosteroid Exposure
Study Overview
Brief Summary
Acute asthma exacerbation is caused by dysregulated pulmonary inflammatory pathways such that standard treatment includes prompt administration of exogenous systemic corticosteroids (SCs), but there remains an ongoing dialogue among the expert medical community regarding the superiority of specific SCs including dose, frequency of administration, route, and delivery. Regimens are often chosen based on provider preference, and different strategies include once-daily dosing (ODD) dexamethasone (DM) 0.6 mg/kg/dose for 2 days, every 6 hours (q6h) DM 0.25 mg/kg/dose for 2 days, and methylprednisolone (MP) 1 mg/kg/dose every 6 hours for 5-days.
To address this knowledge gap, the investigators plan to perform a single-center, phase 2, randomized clinical trial of children 3-17 years of age hospitalized for critical asthma (CA) randomized to one of three regimens above. The study would be powered to evaluate rates of additional prescriptions of SC and also secondarily evaluate quality of life metrics.
Detailed Description
Acute asthma exacerbation is caused by dysregulated pulmonary inflammatory pathways such that standard treatment includes prompt administration of exogenous SCs.17 These agents placate the inflammatory process mediated by airway and systemic leukocytes and have been shown to improve the efficacy of nebulized bronchodilators (i.e., β-2 agonists).18-23 There remains an ongoing dialogue among the expert medical community regarding the superiority of specific SCs including dose, frequency of administration, route, and delivery. While the benefits of SCs for asthma exacerbation have been demonstrated in observational data and rare early phase trials, only one prospective trial conducted by the investigators group 6 has specifically compared IV SCs in the Pediatric Intensive Care Unit (PICU) setting among children hospitalized with CA.1 As a result, specific IV SCs for CA are chosen at the discretion of clinical providers with wide variety observed including ODD DM at 0.6mg/kg/dose for 2 days, q6h DM at 0.25 mg/kg/dose for 2 days, and MP 1mg/kg/dose every 6 hours for 5-days24.
In the investigators early phase clinical trial for SCs for pediatric CA, the investigators compared q6H DM to MP and detected no difference in SC-related adverse events of special interest (AESI), continuous β-2-agonist exposure, and hospital LOS.6 Routine endpoints (i.e., mortality, invasive mechanical ventilation (IMV), and LOS) exhibit limited variability and are rare in cases of pediatric CA. As such, more pragmatic clinical endpoints have been proposed by the investigators research group and others including same cause rehospitalization rates, additional post-discharge SC exposure rate, and markers of QOL including the number of missed school days / sports, and a validated QOL scale (i.e., mini-Pediatric Asthma Quality of Life Questionnaire (PAQLQ12-16). For children discharged from Johns Hopkins All Children's with CA, the investigators estimate rehospitalization rates for CA with receipt of subsequent SCs ≤ 30 days of discharge are between 18-45%, with lower rates observed for MP over DM.
To rigorously address these knowledge gaps, the investigators plan to perform a single-center, phase 2, randomized clinical trial of children 3-17 years of age hospitalized for CA randomized to IV DM (stratified further by q6h and ODD dosing regimens) or IV MP powered to evaluate pragmatic post-discharge endpoints including the rate of additional SC exposure ≤ 30-days of hospital discharge and QOL measures at 30-days after hospital discharge measured by the mini-PAQLQ, the number of missed school days, and number of missed days of play and sports. The investigators will additionally characterize and compare safety (i.e., SC-related AESI and serious adverse events (SAEs) and acute inpatient clinical efficacy (i.e., CA-adjunct intervention free hours) endpoints by randomized SC arms.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 3 Years to 17 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 3-17 years
- •Intensive care unit admission
- •Treatment for critical asthma
Exclusion Criteria
- •History of unrepaired critical congenital heart disease
- •History of cystic fibrosis
- •Active tracheostomy dependence
Arms & Interventions
Dexamethasone Every 6-Hours Dosing for 2 days
Dexamethasone 0.25mg/kg/dose every 6-hours for 8-total doses (i.e., 2 days) Max Dose 16mg per administration
Intervention: Dexamethasone (0.25 mg/kg/dose, Max dose 16mg) every 6-hours (Drug)
Dexamethasone Once Daily Dosing for 2days
Dexamethasone Intravenous 0.6mg/kg/dose once daily for two days (Max Dose: 16mg)
Intervention: Dexamethasone (0.6mg/kg; Max 16mg) Once Daily (Drug)
Methylprednisolone Every 6-hours Dosing for 5-days
Methylprednisolone 1mg/kg every 6-hours for 5-days
Intervention: Methylprednisolone (Drug)
Outcomes
Primary Outcomes
Post-Discharge Systemic Corticosteroid Exposure
Time Frame: Within 30 days of hospital discharge
Aggregate occurrence rate (i.e., risk) of systemic corticosteroid exposures after hospital discharge
Cumulative Adverse Events of Special Interest
Time Frame: From enrollment through 30-days following hospital discharge
Cumulative Adverse Events of Special Interest are inclusive of symptomatic hypertension requiring an antihypertensive agent, symptomatic hyperglycemia requiring insulin, symptomatic agitation requiring antipsychotic agent or sedative administration, adrenal insufficiency, and candidiasis.
Secondary Outcomes
- Pediatric Asthma Quality of Life(Measured at 30-days post hospital discharge)
- Critical Asthma Adjunct Intervention Free Hours(From Enrollment through 30 days post Hospital Discharge)