Intravenous Magnesium: Prompt Use for Asthma in Children Treated in the Emergency Department (IMPACT-ED)

静脉注射镁：在急诊科治疗的儿童哮喘中立即使用 (IMPACT-ED)

• 批准号: 10599339
• 负责人: Michael David Johnson
• 金额: $ 35.57万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10599339
• 关键词: Accident and Emergency department; Acute; Address; Adrenal Cortex Hormones; Adverse event; Albuterol; Applied Research; Asthma; Blood Pressure; Blood Pressure Monitors; Blood specimen; Breathing; Bronchodilator Agents; Child; Childhood; Childhood Asthma; Chronic Disease; Clinical; Clinical Trials; Complex; Consent; Cost Savings; Critically ill children; Data; Development; Devices; Direct Costs; Dose; Drug Kinetics; Emergency Care; Enrollment; Evaluation; Facilities and Administrative Costs; Funding; Future; Goals; Guidelines; Health Care Costs; Home; Hospitalization; Hospitalized Child; Hypotension; Infusion procedures; Inhalation; Intervention; Intravenous; Intravenous Bolus; Knowledge; Length; Life; Magnesium; Magnesium Sulfate; Measures; Medicine; Meta-Analysis; Modeling; Monitor; Multicenter Trials; National Heart, Lung, and Blood Institute; Needles; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pilot Projects; Placebos; Positioning Attribute; Procedures; Protocols documentation; Publishing; Randomized; Recommendation; Reporting; Research; Respiratory distress; Safety; Saline; Schools; Serum; Serum Magnesium Level; Sickle Cell Anemia; Site; Standardization; Steroids; Study Subject; Testing; Translating; Work; arm; childcare allowance; clinical database; design; double-blind placebo controlled trial; experience; improved; intravenous administration; ionization; novel; participant enrollment; patient safety; pediatric emergency; pharmacodynamic model; pharmacokinetic model; pharmacologic; pilot trial; prevent; prospective; randomized placebo controlled trial; randomized placebo-controlled clinical trial; randomized trial; standard care; trial planning

PROJECT SUMMARY ABSTRACT Asthma is the most common chronic illness of childhood and a leading cause of hospitalization and healthcare costs for children. Most children hospitalized for asthma first receive breathing treatments and steroid medicines in an emergency department (ED) according to national guidelines. An additional medicine, intravenous magnesium sulfate (IVMg), may help severely sick children avoid hospitalization. National asthma guidelines recommend IVMg for severely sick children, but note a lack of consistent evidence to support this recommendation. Only about one in four children hospitalized for asthma received IVMg in the ED. Estimates of the potential effects of broader use of IVMg on hospitalization are limited by the small size of prior trials, but increased use could potentially avoid 18,000 hospitalizations each year, producing direct cost savings of $65 million yearly in addition to saving significant indirect costs of missed school and parental work. A few major questions remain about IVMg. First, it has not been tested early in ED treatment, when the impact on hospitalization would be greatest. Second, the clinical impact of hypotension, a driver of low utilization, is not characterized in prior trials or clinical databases. Third, no trials have compared different IVMg doses or measured serum magnesium levels to optimize dosing, so the most effective dose is unknown. All prior trials of IVMg in children with asthma have been small. A large randomized, placebo-controlled clinical trial of IVMg that could answer whether IVMg can reduce hospitalization might be challenging for a few reasons. First, enrolling patients fast enough to give IVMg early in ED treatment is challenging. Second, understanding blood pressure changes after IVMg is essential to plan safety monitoring for a larger trial. Third, little pharmacologic information has been gathered to guide the doses of IVMg to be tested. We must conduct a small pilot clinical trial to test our procedures and gather necessary information to plan the large trial. The Pediatric Emergency Care Applied Research Network (PECARN) is a network of children’s EDs that has conducted similar research involving acutely ill children. Our goals in this project are to: 1. Demonstrate the feasibility of enrolling children in the ED with severe acute asthma in a multicenter, randomized, controlled trial of placebo, low-dose IVMg, or high-dose IVMg. 2. Demonstrate the feasibility of timely delivery of study medication to enrolled patients and assessment of blood pressure and associated adverse events in a standardized protocol. 3. Externally validate a previously constructed PK model and develop a combined PK/PD model for IVMg using magnesium (total and ionized) serum concentrations and their correlation with measures of safety and respiratory distress in children with asthma. After completing this pilot trial in three sites, we will plan a multi-center randomized trial of IVMg in children with severe acute asthma at more sites to enroll enough children to know if IVMg can reduce hospitalization.

项目摘要 哮喘是儿童最常见的慢性疾病，也是住院和医疗保健的主要原因 孩子的费用。大多数哮喘住院儿童首先接受呼吸治疗和类固醇 根据国家指南，在急诊科（艾德）使用药物。一种额外的药物， 静脉注射硫酸镁（IVMg）可能有助于重症儿童避免住院治疗。全国哮喘 指南建议重症儿童使用IVMg，但指出缺乏一致的证据支持这一点 推荐只有大约四分之一的哮喘住院儿童在急诊室接受了IVMg治疗。 更广泛使用IVMg对住院治疗的潜在影响受到先前试验规模小的限制，但 增加使用每年可能避免18，000例住院治疗，直接节省65美元的费用 此外，每年还节省了大量的缺课和父母工作的间接费用。 关于IVMg仍然存在一些主要问题。首先，它没有在艾德治疗的早期进行测试， 住院治疗是最好的。其次，低血压的临床影响，低利用率的驱动因素， 在先前的试验或临床数据库中未表征。第三，没有试验比较不同的IVMg剂量或 测量血清镁水平以优化剂量，因此最有效剂量未知。 所有先前在哮喘儿童中进行的IVMg试验都是小规模的。一项大型随机、安慰剂对照临床研究 IVMg的试验可以回答IVMg是否可以减少住院治疗，这对一些人来说可能具有挑战性 原因首先，在艾德治疗早期足够快地招募患者以给予IVMg是具有挑战性的。第二、 了解IVMg后的血压变化对于计划大型试验的安全性监测至关重要。第三、 几乎没有收集到药理学信息来指导待测试的IVMg剂量。我们必须进行 一个小型的试点临床试验，以测试我们的程序，并收集必要的信息，以计划大型试验。 儿科急诊应用研究网络（PECARN）是一个儿童急诊网络， 对患有急性病的儿童进行了类似的研究。我们在这个项目中的目标是： 1.证明在一个有严重急性哮喘的儿童中招募艾德的可行性， 安慰剂、低剂量IVMg或高剂量IVMg的多中心、随机、对照试验。 2.证明及时向入组患者提供研究药物的可行性， 在标准化方案中评估血压和相关不良事件。 3.外部验证先前构建的PK模型，并开发PK/PD组合模型， 使用镁（总和离子）血清浓度的IVMg及其与 哮喘儿童的安全措施和呼吸窘迫。 在三个中心完成这项初步试验后，我们将计划在患有以下疾病的儿童中进行IVMg的多中心随机试验： 在更多的研究中心招募足够的儿童来了解IVMg是否可以减少住院治疗。