Critical Illness
Conditions
Keywords
Critical illness, Magnesium, Atrial fibrillation, Protocols
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. 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.
Interventions
Magnesium sulfate is used in both arms for magnesium replacement.
DRUGMagnesium oxide
In the higher-target arm, magnesium oxide 420mg po q12h x 2 is one of the options available for magnesium replacement when magnesium levels lie between 0.75 and 0.95mmol/L.
DRUGMagnesium glucoheptonate
Magnesium glucoheptonate 30mL po q12h x 2 is an oral option for magnesium replacement in the higher-target arm.
Sponsors
Scarborough Health Network
Lakeridge Health Corporation
Scarborough General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Pragmatic comparative effectiveness trial
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 16 years or older * Admission orders written to a medical-surgical intensive care unit at a participating site * Magnesium replacement protocol ordered
Exclusion criteria
* Prior enrollment in or withdrawal from MAGNOLIA trial * Sustained ventricular tachycardia * Pre-eclampsia * Myasthenia gravis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Discharge destination | 90 days | Categorical variable noting discharge destination on index hospitalization (eg home, retirement home, long-term care, acute care hospital, etc). |
| Magnesium administrations - by mass | 30 days | Elemental magnesium administered (g per day) |
| Organ-support free days | 30 days | Number of days alive and free of invasive ventilation, vasopressors, and renal replacement therapy |
| ICU-free days | 30 days | Number of days alive and not in ICU |
| Invasive ventilation-free days | 30 days | Number of days alive and free of invasive ventilation |
| 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 |
| Ventricular arrhythmia | 30 days | Binary outcome noting the occurence of either sustained ventricular tachycardia or ventricular fibrillation in ICU (1), or not (0). |
| Magnesium administrations - route | 30 days | Route of magnesium administrations each day (PO vs IV) |
| 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 per day) |
| 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 | 60 days | Hospital mortality |
| Hospital length of stay | 90 days | Length of hospitalization, including transfers within the health network. |
| 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. |
Countries
Canada
Contacts
Primary ContactJoshua Craig
Outcome results
None listed