Pediatric Asthma Trial of Corticosteroid Heterogeneity (PATCH): Trial of Dexamethasone Versus Methylprednisolone for Pediatric Critical Asthma

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Dexamethasone (0.6mg/kg; Max 16mg) Once Daily
  For this intervention, Dexamethasone will be administered at 0.6mg/kg/dose once daily for a maximum dose of 16 mg for 2 days
• Препарат Dexamethasone (0.25 mg/kg/dose, Max dose 16mg) every 6-hours
  For this intervention, Dexamethasone will be administered at 0.25mg/kg/dose every 6 hours for a maximum dose of 16 mg for 2 days
• Препарат Methylprednisolone
  For this intervention, Methylprednisolone will be administered at 1 mg/kg/dose every 6 hours for a maximum dose of 60 mg for 5 days

Первичные конечные точки

• Post-Discharge Systemic Corticosteroid Exposure [Срок оценки: Within 30 days of hospital discharge]
• Cumulative Adverse Events of Special Interest [Срок оценки: From enrollment through 30-days following hospital discharge]

Вторичные конечные точки (2)

• Pediatric Asthma Quality of Life [Срок оценки: Measured at 30-days post hospital discharge]
• Critical Asthma Adjunct Intervention Free Hours [Срок оценки: From Enrollment through 30 days post Hospital Discharge]

Критерии участия

Критерии включения

• Age 3-17 years
• Intensive care unit admission
• Treatment for critical asthma

Критерии исключения

• History of unrepaired critical congenital heart disease
• History of cystic fibrosis
• Active tracheostomy dependence

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Johns Hopkins All Children's Hospital — St. Petersburg

Публикации

• Sellers AR, Roddy MR, Darville KK, Sanchez-Teppa B, McKinley SD, Sochet AA. Dexamethasone for Pediatric Critical Asthma: A Multicenter Descriptive Study. J Intensive Care Med. 2022 Nov;37(11):1520-1527. doi: 10.1177/08850666221082540. Epub 2022 Mar 3. PMID 35236174
• Roddy MR, Sellers AR, Darville KK, Teppa-Sanchez B, McKinley SD, Martin M, Goldenberg NA, Nakagawa TA, Sochet AA. Dexamethasone versus methylprednisolone for critical asthma: A single center, open-label, parallel-group clinical trial. Pediatr Pulmonol. 2023 Jun;58(6):1719-1727. doi: 10.1002/ppul.26386. Epub 2023 Mar 17. PMID 36929864
• Fowler CA, Ryder JM, Roberts AR, Sochet AA, Roddy MR. Methylprednisolone dosing for pediatric critical asthma: a single-center cohort study. J Asthma. 2024 Dec;61(12):1672-1678. doi: 10.1080/02770903.2024.2375276. Epub 2024 Jul 6. PMID 38954523

Идентификаторы

NCT: NCT07455396 · IRB00544439

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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