Magnesium Trial in Acute Asthma in Emergency Department

Обзор

Despite optimal initial emergency department (ED) therapy, 50% of children with severe acute asthma have ongoing moderate-severe respiratory distress. Guidelines recommend intravenous magnesium (IVMg) for them, yet evidence for IVMg efficacy is scant and disparate. While early small Randomized Controlled Trials (RCTs) suggested hospitalization benefit, recent large observational studies found no association between IVMg and improved outcomes. IVMg therapy is resource-intensive, can cause hypotension and demands close monitoring. Previous RCTs only assessed early Mg effect at 1-2 hours, overlooked the peak effect of key co-interventions such as corticosteroids and did not use validated scores. IVMg use is variable and often delayed until ≥4 hours after ED therapy is started and after the hospitalization decision has been made. Thus, in observational studies children given IVMg are 6-10 times more likely to be hospitalized; these studies have major confounding and the true IVMg treatment effect is thus unknown. To conclusively determine if IVMg alters the exacerbation course, it must be given early, and the primary outcome measure should be the severity of respiratory distress measured at the peak effect of key co-interventions to focus on a clinically meaningful and objective effect. The Pediatric Respiratory Assessment Measure (PRAM)-a valid, discriminative, reproducible and responsive-to-change instrument-is thus the ideal primary outcome measure. Hospitalization outcome has major confounding by indication and MD perceptions. Primary Aim: In children with acute asthma remaining in moderate-severe distress after 1 hour of initial ED therapy, is early IVMg therapy associated with a significantly greater improvement in respiratory distress, measured by PRAM, at 2 hours after starting the intervention, compared to placebo? Hypothesis: IVMg will yield significantly greater PRAM improvement of ≥1.0 point than placebo. Expected Outcomes: This trial will clarify if there is an incremental benefit of IVMg in decreasing respiratory distress in pediatric refractory acute asthma. A positive result will establish a proven standard of care for this indication, with a need for Knowledge Translation (KT) to implement routine early IVMg therapy. A negative result will lead to de-implementation of IVMg which may also lead to cost savings.

Подробное описание

The investigators propose a 6-centre randomized, double-blind, placebo-controlled trial. Two groups will be compared: IV Mg sulfate and IV (intravenous) 0.9% saline placebo. After initial therapy with the systemic Corticosteroids (CSs) routinely used for acute asthma management at a given site, 3 treatments with inhaled salbutamol and ipratropium (ipratropium use as per local practice), eligible patients with PRAM ≥5 will, under the care of the research nurse, receive a 30-minute IV infusion of 75 mg/kg of Mg sulfate (maximum 2.0 g) \[experimental group\] or an identical volume of 0.9% saline \[control group\]. Outcomes will be measured during the 180-minute observational period in the ED and at 72 hours post ED discharge.

Вмешательства

• Препарат magnesium sulfate
  After initial therapy with the systemic CSs routinely used for acute asthma management at a given site, 3 treatments with inhaled salbutamol and ipratropium, eligible patients with PRAM ≥5 will, under the care of the research nurse, receive a 30-minute IV infusion of 75 mg/kg of Mg sulfate(maximum 2.0 g) \[experimental group\]
• Препарат Normal Saline
  After initial therapy with the systemic CSs routinely used for acute asthma management at a given site, 3 treatments with inhaled salbutamol and ipratropium, eligible patients with PRAM ≥5 will, under the care of the research nurse, receive a 30-minute IV infusion of 0.9% saline \[control group\].

Первичные конечные точки

• Pediatric Respiratory Assessment Measure (PRAM) score: This score ranges from 0-12. A score from 0-3 is mild, 4-7 moderate and 8-12 severe. A low score is a better outcome and a high score is a worse outcome. [Срок оценки: The primary outcome measure will be the PRAM score at 120 minutes post start of experimental therapy.]

Вторичные конечные точки (9)

• Changes in PRAM score [Срок оценки: Changes in PRAM score from baseline (pre intervention) to 30, 60, 120, 180 minutes after start of experimental therapy]
• Hospitalization for asthma at the index ED visit [Срок оценки: Up to 24 hours after starting experimental therapy]
• Changes in respiratory rate [Срок оценки: From baseline (pre-intervention) to 30,60,120 and 180 minutes post intervention (respiratory rate )]
• Changes in oxygen saturation [Срок оценки: From baseline (pre-intervention) to 30,60,120 and 180 minutes post intervention ( oxygen saturation)]
• Changes in blood pressure [Срок оценки: From baseline (pre-intervention) to 10,20,30,60,120, and 180 minutes post intervention (blood pressure).]
• PRAM denoting mild asthma (≤ 3 points is a widely accepted discharge criterion). [Срок оценки: at 120 minutes post intervention]
• Hospitalization for asthma at any medical facility [Срок оценки: within 72 hours post- ED discharge]
• Unscheduled asthma-related visits to any health care provider [Срок оценки: within 72 hours post- ED discharge]
• Hospital length of stay. [Срок оценки: From presentation at the Emergency Department triage to the time of hospital discharge, up to 4 weeks.]

Критерии участия

Критерии включения

• Age 2.00-17.99 years (prior to 18th birthday),
• Diagnosis of asthma, defined as an asthma or probable asthma diagnosis/asthma-like phenotype made by a physician (this includes ED physician) in a patient who in the opinion of the treating ED physician requires therapy for acute asthma in the ED (GINA asthma guidelines, 2024).
• Moderate-severe asthma after initial therapy with 3 treatments of inhaled salbutamol and ipratropium, defined as an eligibility PRAM ≥5, indicating a strong association with hospitalization.

Критерии исключения

• Receipt of IVMg within 24 hours prior to ED arrival.
• Need for airway support on arrival. (Airway support on arrival meeting exclusion criteria will include immediate need for high flow nasal cannula therapy, non-invasive CPAP/bi-PAP ventilation or invasive ventilation with endotracheal intubation, as decided by the attending Emergency Department (ED) physician. Supplemental oxygen therapy will not represent an exclusion criterion.)
• Known renal, chronic pulmonary, neurologic, cardiac or systemic disease: these may influence outcomes after Mg.
• Known hypersensitivity to Mg sulfate.
• Previous enrollment.
• Poor mastery of English and/or French language precluding informed consent understanding.
• No phone/email; unavailable for follow-up

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

Четверное слепое

Основная цель

Лечение

Центры проведения

Канада · 6 центров

• Alberta Children's Hospital — Calgary
• Stollery Children's Hospital — Edmonton
• McMaster Children's Hospital — Hamilton
• Children's Hospital of Eastern Ontario — Ottawa
• The Hospital for Sick Children — Toronto
• CHU-Sainte Justine Hospital — Montreal

Идентификаторы

NCT: NCT06785272 · 5274

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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