Effect of Protocolized Magnesium Replacement in Critically Ill Patients on Mortality and Atrial Fibrillation: the MAGNOLIA Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 3,253
- 试验地点
- 11
- 主要终点
- 30-day ordinal composite of hospital mortality and days free of atrial fibrillation in ICU
研究概览
简要总结
In patients with critical illness, such as severe infections, heart attacks, or respiratory failure, most intensive care units (ICUs) measure magnesium levels and give supplemental doses of magnesium when levels are below certain targets. However, the best targets are unknown. The goal of this clinical trial is to study protocols for magnesium supplementation in people with critical illness, comparing a protocol with higher target level to a protocol with a lower target level.
The main question this study aims to answer is whether magnesium supplementation protocols targeting a higher or lower level lead to better 30-day survival and less atrial fibrillation.
Participants will not have to do any specific tasks, undergo any additional tests, or complete any surveys.
详细描述
Background: Measurement of serum magnesium levels, and administration of supplemental magnesium when levels are below target, is a common element of routine care for critically ill patients. However, targets for replacement vary, and the targets that lead to the best outcomes are unknown.
Methods: Multi-center open-label parallel group randomized controlled superiority trial of adult critically ill patients receiving protocolized magnesium replacement, comparing a higher target (>0.95mmol/L) to a lower target (>0.7mmol/L). The trial will be embedded into the electronic medical record (EMR) at 5 hospitals across 2 health networks in Ontario, Canada, with a shared EMR. Patients aged 16 years or older who have ICU admission orders and an order for the magnesium replacement protocol will be included. Patients with pre-eclampsia, sustained ventricular tachycardia, or neuromuscular junction disease will be excluded. The primary outcome will be an ordinal composite, evaluated at 30 days, composed of death and the number of days free of atrial fibrillation or flutter in ICU. Secondary outcomes will include ventricular arrhythmia and antiarrhythmics administered; receipt of vasopressors, ventilation, and new renal replacement therapy in ICU; lengths of ICU and hospital stay; hospital mortality at 60 and 90 days, magnesium levels, and magnesium supplementation. Analyses will use Bayesian regression with weakly skeptical priors and an intention-to-treat approach. Because both targets lie within the standard of care, the trial will use opt-out consent. Screening will be integrated with the EMR, such that when a patient meets inclusion criteria, a pop-up will appear for the ordering clinician. After the clinician confirms eligibility, the patient will be randomized and assigned to their target. Outcome ascertainment will occur within the EMR.
Discussion: This randomized controlled trial addresses an important uncertainty regarding routine care in the ICU with an EMR-embedded design. The innovative EMR-embedded design facilitates the large sample sizes and comprehensive, equitable recruitment needed for a trial evaluating a routine care intervention, and will lead to seamless integration with routine care upon trial completion.
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
- None
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 16 years or older
- •Admission orders written to a medical-surgical intensive care unit at a participating site
- •Magnesium replacement protocol ordered
排除标准
- •Prior enrollment in or withdrawal from MAGNOLIA trial
- •Sustained ventricular tachycardia
- •Pre-eclampsia
- •Myasthenia gravis
研究组 & 干预措施
Lower target (>0.7mmol)
Protocolized magnesium replacement according to magnesium level as follows: for 0.45 - 0.70mmol/L, magnesium sulfate 4g IV x 1 and repeat magnesium level the next day; for < 0.45mmol/L, magnesium sulfate 6g IV x 1, alert most responsible physician, and repeat level in 4 hours.
干预措施: Magnesium sulfate administration (Drug)
Higher target (>0.95mmol/L)
Protocolized magnesium replacement according to magnesium level as follows: for 0.75-0.95mmol/L, magnesium sulfate 2g IV x 1, magnesium oxide 420 mg po q12h x 2, or magnesium glucoheptonate 30mL po q12h x 2; for 0.45 - 0.74mmol/L, magnesium sulfate 4g IV x 1 and repeat magnesium level the next day; for < 0.45mmol/L, magnesium sulfate 6g IV x 1, alert most responsible physician, and repeat level in 4 hours.
干预措施: Magnesium sulfate administration (Drug)
Higher target (>0.95mmol/L)
Protocolized magnesium replacement according to magnesium level as follows: for 0.75-0.95mmol/L, magnesium sulfate 2g IV x 1, magnesium oxide 420 mg po q12h x 2, or magnesium glucoheptonate 30mL po q12h x 2; for 0.45 - 0.74mmol/L, magnesium sulfate 4g IV x 1 and repeat magnesium level the next day; for < 0.45mmol/L, magnesium sulfate 6g IV x 1, alert most responsible physician, and repeat level in 4 hours.
干预措施: Magnesium oxide (Drug)
Higher target (>0.95mmol/L)
Protocolized magnesium replacement according to magnesium level as follows: for 0.75-0.95mmol/L, magnesium sulfate 2g IV x 1, magnesium oxide 420 mg po q12h x 2, or magnesium glucoheptonate 30mL po q12h x 2; for 0.45 - 0.74mmol/L, magnesium sulfate 4g IV x 1 and repeat magnesium level the next day; for < 0.45mmol/L, magnesium sulfate 6g IV x 1, alert most responsible physician, and repeat level in 4 hours.
干预措施: Magnesium glucoheptonate (Drug)
结局指标
主要结局
30-day ordinal composite of hospital mortality and days free of atrial fibrillation in ICU
时间窗: 30 days after enrollment.
This is an ordinal outcome with 32 levels ranging from -1 (worst) to 30 (best). It is evaluated at 30 days. The worst outcome (-1) corresponds to mortality in hospital within 30 days from trial enrollment. Among patients who do not die in hospital by day 30, we count the number of days when they did not have atrial fibrillation in the ICU. For example, a survivor who never had atrial fibrillation in ICU would be scored as "30." A survivor who had 5 days of atrial fibrillation in ICU would be scored as "25." A patient who is discharged from hospital, either to home or transferred to another site, but is readmitted to a study hospital and dies within 30 days of enrollment, would be counted as having had hospital mortality. This stipulation is relevant because of the frequency of transfers between sites within a health network, due to regionalization of services such as vascular surgery, thoracic surgery, dialysis, and angiography.
次要结局
- Magnesium administrations(30 days)
- Fluid balance(30 days)
- DOOR 1: Death and arrhythmia(30 days)
- ICU-free days(30 days)
- Vasopressor-free days(30 days)
- Renal replacement therapy-free days(30 days)
- Magnesium and potassium levels in ICU(30 days)
- DOOR 2: Survival, organ dysfunction, hospitalization, discharge(30 days)
- Hospital mortality(90 days)
- Hospital length of stay(90 days)
- Hospital mortality(60 days)
- Discharge destination(90 days)
- Hospital mortality(90 days)
- Hospital length of stay(90 days)
- Organ-support free days(30 days)
- ICU-free days(30 days)
- Invasive ventilation-free days(30 days)
- Vasopressor-free days(30 days)
- Renal replacement therapy-free days(30 days)
- Ventricular arrhythmia(30 days)
- Intravenous antiarrhythmics(30 days)
- Magnesium and potassium levels in ICU(30 days)
- Magnesium administrations(30 days)
- Fluid balance(30 days)
- DOOR 1: Death and arrhythmia(30 days)
- DOOR 2: Survival, organ dysfunction, hospitalization, discharge(30 days)
- Discharge destination(90 days)
- Magnesium administrations - by mass(30 days)
- Magnesium administrations - route(30 days)
研究者
Christopher Yarnell
Intensivist and Researcher
Scarborough General Hospital