Intravenous Magnesium: Prompt Use for Asthma in Children Treated in the Emergency Department
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 3
- 主要终点
- Enrollment
研究概览
简要总结
Many children currently being hospitalized with severe asthma could potentially avoid hospitalization and be sent home if their treatment in the emergency department was more effective. The investigators will conduct a pilot trial that will lead to a larger study to conclusively answer whether a simple and inexpensive medicine, intravenous magnesium sulfate, can be used in the emergency department to prevent hospitalization for these children.
详细描述
5.4.1 Acquisition The specific study agent to be used in this pilot trial is Magnesium Sulfate in Water for Injection, a sterile, nonpyrogenic solution of magnesium sulfate heptahydrate in water. Study agent will be acquired by each hospital's research pharmacy from Pfizer, Inc as a solution of magnesium sulfate in water at 80 mg/mL. Agent will be shipped directly from Pfizer to each study hospital pharmacy.
5.4.2 Preparation, Storage & Labeling Doses for each IVMg arm will be prepared in identical manner, by drawing a specified volume of Intravenous Magnesium Sulfate (IVMg) from the commercial container using sterile technique and mixing in a polyvinylchloride container with a specified volume of sterile water. For the 50 mg/kg arm, this will be accomplished by mixing 25 mL of IVMg (80 mg/mL) with 15 mL of sterile water for a final concentration of 50 mg/mL and volume of 40 mL. For the 75 mg/kg arm, this will be accomplished by mixing 37.5 mL of IVMg (80 mg/mL) with 2.5 mL of sterile water for a final concentration of 75 mg/mL and volume of 40 mL. For the placebo arm, 40 mL of 0.9% sodium chloride solution will be drawn into a polyvinylchloride container identical in appearance to the containers used for the IVMg arms. Each prepared dose will be labeled according to the sequential randomization scheme and stored according to local pharmacy procedure. Unused doses prepared locally will be replaced after one week of storage.
5.4.3 Dosing Schedule
After randomization the institutional pharmacist will draw equivolumetric dosages (1 mL/kg, with max of 40 mL) from previously prepared vials. Enrolled subjects will be randomized to one of three arms:
- IVMg 75 mg/kg arm: 75 mg/kg (max 3 gm) infused over 20 minutes through a peripheral IV catheter
- IVMg 50 mg/kg arm: 50 mg/kg (max 2 gm) infused over 20 minutes through a peripheral IV catheter
- Placebo arm: 1 mL/kg (max 40 ml) of normal saline over 20 minutes through a peripheral IV catheter 5.4.4 Dose Modification for Potential Toxicity Clinicians will not administer IVMg to enrolled subjects outside of the study protocol until study outcomes have been determined 2 hours after the start of the infusion. The half-life of IVMg is approximately 2 hours.49 Repeated-dose protocols in an ICU setting that gave as much as 125 mg/kg IVMg to children with asthma over two hours produced no hypotension or other serious adverse effects.47 Because of this margin of safety, open-label IVMg 50 mg/kg can be administered safely 2 hours after the study infusion under strict study monitoring protocols without need for unblinding.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Doses will be prepared ahead of time by an investigational pharmacist, arms will be identical in appearance, and clinicians administering the study drug will be blinded to the study arm the patient receives.
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
75 mg/kg
Doses for each IVMg arm will be prepared in identical manner, by drawing a specified volume of IVMg from the commercial container using sterile technique and mixing in a polyvinylchloride container with a specified volume of sterile water. For the 75 mg/kg arm, this will be accomplished by mixing 37.5 mL of IVMg (80 mg/mL) with 2.5 mL of sterile water for a final concentration of 75 mg/mL and volume of 40 mL. After randomization the institutional pharmacist will draw dosages (1 mL/kg, with max of 40 mL) from previously prepared vials. The dose will be delivered by the clinical nurse over 20 minutes through a peripheral IV.
干预措施: Magnesium Sulfate, Heptahydrate (Drug)
50 mg/kg
Doses for each IVMg arm will be prepared in identical manner, by drawing a specified volume of IVMg from the commercial container using sterile technique and mixing in a polyvinylchloride container with a specified volume of sterile water. For the 50 mg/kg arm, this will be accomplished by mixing 25 mL of IVMg (80 mg/mL) with 15 mL of sterile water for a final concentration of 50 mg/mL and volume of 40 mL. After randomization the institutional pharmacist will draw dosages (1 mL/kg, with max of 40 mL) from previously prepared vials. The dose will be delivered by the clinical nurse over 20 minutes through a peripheral IV.
干预措施: Magnesium Sulfate, Heptahydrate (Drug)
Placebo
For the placebo arm, 40 mL of 0.9% sodium chloride solution will be drawn into a polyvinylchloride container identical in appearance to the containers used for the IVMg arms. After randomization the institutional pharmacist will draw dosages (1 mL/kg, with max of 40 mL) from previously prepared vials. The dose will be delivered by the clinical nurse over 20 minutes through a peripheral IV.
干预措施: 0.9% saline (Drug)
结局指标
主要结局
Enrollment
时间窗: 7 months of enrollment.
The primary outcome in this pilot trial is demonstration of the ability to enroll severely ill children with asthma in a randomized trial requiring timely delivery of IVMg or placebo. The investigators anticipate that the primary outcome of the future large trial will be the proportion of children hospitalized at the index visit in each arm.
次要结局
- Hospitalization(Actual disposition from chart review 1 week after enrollment.)
- Hospitalization Anticipated by Treating Physician 2 Hours After Start of Study Infusion(Physician-anticipated hospitalization 2 hours after the start of study drug infusion)
- Adverse Events and Safety Profiles - Hypotension and Perfusion(2 hours after study drug infusion.)
- Rescue Therapies Used During ED Care - SQ or IM Epinephrine(One week after enrollment)
- Return ED Visit(Within 10 days after ED discharge)
- Baseline Serum Magnesium(At IV placement before infusion of study drug)
- Post-infusion Serum Magnesium 1(20-40 minutes after the start of study drug infusion)
- Post-infusion Ionized Magnesium 1(20-40 minutes after the start of study drug infusion)
- Baseline Ionized Magnesium(At IV placement before infusion of study drug)
- Post-infusion Serum Magnesium 2(90-150 minutes after the start of study drug infusion)
- Post-infusion Ionized Magnesium 2(90-150 minutes after the start of study drug infusion)
- Rescue Therapies Used During ED Care - IV Epinephrine(One week after enrollment)
- Rescue Therapies Used During ED Care - IV Terbutaline(One week after enrollment)
- Rescue Therapies Used During ED Care - IV Magnesium(One week after enrollment)
- Adverse Events and Safety Profiles - Supraventricular Tachycardia(1 week)
- Adverse Events and Safety Profiles - Abdominal Discomfort(1 week)
- Adverse Events and Safety Profiles - Vomiting(1 week)
- Adverse Events and Safety Profiles - Fatigue(1 week)
- Adverse Events and Safety Profiles - Hypokalemia(1 week)
- Adverse Events and Safety Profiles - Delirium(1 week)
- Adverse Events and Safety Profiles - Hypoxia(1 week)
- Adverse Events and Safety Profiles - Respiratory Distress(1 week)
- Adverse Events and Safety Profiles - Metabolic Acidosis(1 week)
- Adverse Events and Safety Profiles - Duodenal Ulcer Perforation(1 week)
研究者
Mike Johnson
Associate Professor of Pediatrics
University of Utah