Effect of Protocolized Magnesium Replacement on Mortality and Atrial Fibrillation in Critically Ill Patients
- Conditions
- Critical Illness
- Interventions
- Drug: Lower target (>0.7mmol/L)Drug: Higher target (>0.95mmol/L)
- Registration Number
- NCT07173855
- Lead Sponsor
- Scarborough General Hospital
- Brief Summary
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.
- Detailed Description
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. We will include patients aged 16 years or older who have ICU admission orders, including an order for the magnesium replacement protocol. 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. For analyses, we will use Bayesian regression with weakly skeptical priors and an intention-to-treat approach. Because both targets lie within the standard of care, we will use an opt-out consent approach. 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 3253
- Age 16 years or older
- Admission orders written to a medical-surgical intensive care unit at a participating site
- Magnesium replacement protocol ordered
- Prior enrollment in or withdrawal from MAGNOLIA trial
- Sustained ventricular tachycardia
- Pre-eclampsia
- Myasthenia gravis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lower target (>0.7mmol) Lower target (>0.7mmol/L) Protocolized magnesium replacement when magnesium level is 0.70mmol/L or less. Higher target (>0.95mmol/L) Higher target (>0.95mmol/L) Protocolized magnesium replacement when magnesium level is 0.95mmol/L or less.
- Primary Outcome Measures
Name Time Method 30-day ordinal composite of hospital mortality and days free of atrial fibrillation in ICU 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.
- Secondary Outcome Measures
Name Time Method ICU-free days 30 days Number of days alive and not in ICU
Organ-support free days 30 days Number of days alive and free of invasive ventilation, vasopressors, and renal replacement therapy
Invasive ventilation-free days 30 days Number of days alive and free of invasive ventilation
Ventricular arrhythmia 30 days Binary outcome noting the occurence of either sustained ventricular tachycardia or ventricular fibrillation in ICU (1), or not (0).
Intravenous antiarrhythmics 30 days Binary variable noting administration of intravenous antiarrhythmics in ICU (1) or not (0). Intravenous antiarrhythmics include amiodarone, metoprolol, esmolol, diltiazem, procainamide, lidocaine, flecainide, adenosine, digoxin.
Vasopressor-free days 30 days Days alive and not receiving vasopressors
Renal replacement therapy-free days 30 days Days alive and not receiving renal replacement therapy in the ICU
Magnesium and potassium levels in ICU 30 days Daily levels of magnesium and potassium in ICU
Magnesium administrations 30 days Magnesium administrations while in ICU (number, route, dose).
Fluid balance 30 days Daily fluid balance (sum of all liquid intakes minus the sum of all liquid outputs).
DOOR 1: Death and arrhythmia 30 days This is a desirability of outcome ordinal ranking (DOOR) outcome. The possible binary levels are, from worst to best: death, ventricular arrhythmia, atrial fibrillation or flutter, none of the above.
DOOR 2: Survival, organ dysfunction, hospitalization, discharge 30 days This is a desirability of outcome ordinal ranking (DOOR) outcome. The binary levels are, ordered from best to worst: discharge home, discharge to location other than home, ongoing hospital admission, persistent organ dysfunction in ICU, death.
Hospital mortality 90 days Hospital mortality
Hospital length of stay 90 days Length of hospitalization, including transfers within the health network.
Discharge destination 90 days Categorical variable noting discharge destination on index hospitalization (eg home, retirement home, long-term care, acute care hospital, etc).
Trial Locations
- Locations (5)
Lakeridge Health Ajax-Pickering
🇨🇦Ajax, Ontario, Canada
Lakeridge Health Oshawa
🇨🇦Oshawa, Ontario, Canada
Scarborough Centenary Hospital
🇨🇦Toronto, Ontario, Canada
Scarborough General Hospital
🇨🇦Toronto, Ontario, Canada
Scarborough Birchmount Hospital
🇨🇦Toronto, Ontario, Canada
Lakeridge Health Ajax-Pickering🇨🇦Ajax, Ontario, Canada