Critical IllnessPhase 4MAGNOLIANCT07173855
Effect of Protocolized Magnesium Replacement on Mortality and Atrial Fibrillation in Critically Ill Patients
A Phase 4 study testing Magnesium sulfate administration, Magnesium oxide and Magnesium glucoheptonate in people with Critical Illness, run by Scarborough General Hospital at 6 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Critical Illness
- What is being tested?
- Magnesium sulfate administration, Magnesium oxide and Magnesium glucoheptonate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,853 participants
- Where
- 6 sitesCanada
- Study dates
- 25 Nov 2025to 1 Jun 2027
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 16 years or older
- Admission orders written to a medical-surgical intensive care unit at a participating site
- Magnesium replacement protocol ordered
Who cannot join
- Prior enrollment in or withdrawal from MAGNOLIA trial
- Sustained ventricular tachycardia
- Pre-eclampsia
- Myasthenia gravis
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
Canada6 sites, 6 recruiting
- Recruiting
Lakeridge Health Ajax-Pickering
Ajax, Ontario, L1S 2J4
Sarah Dulmage, 9055768711 ext. 32748, sdulmage@lh.ca
- Recruiting
Lakeridge Health Bowmanville
Bowmanville, Ontario, L1C 2N3
Sarah Dulmage, 905-576-8711 ext. 32748, sdulmage@lh.ca
- Recruiting
Lakeridge Health Oshawa
Oshawa, Ontario, L1G 8A2
Sarah Dulmage, 905-576-8711 ext. 32748, sdulmage@lh.ca
- Recruiting
Scarborough Centenary Hospital
Toronto, Ontario, M1E 4B9
Joshua Craig, 4164382911 ext. 86006, jcraig@shn.ca
- Recruiting
Scarborough General Hospital
Toronto, Ontario, M1P2V5
Joshua Craig, 4164382911 ext. 86006, jcraig@shn.ca
- Recruiting
Scarborough Birchmount Hospital
Toronto, Ontario, M1W 3W3
Joshua Craig, 4164382911 ext. 86006, jcraig@shn.ca
About this study
Official title: Effect of Protocolized Magnesium Replacement in Critically Ill Patients on Mortality and Atrial Fibrillation: the MAGNOLIA Randomized Controlled Trial
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.
Read the 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.
- Conditions
- Critical Illness
- Being tested
- Magnesium sulfate administration, Magnesium oxide, Magnesium glucoheptonate
- Keywords
- Critical illness, Magnesium, Atrial fibrillation, Protocols
- Medical subject headings
- Critical Illness, Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnesium sulfate administrationDrug
Magnesium sulfate is used in both arms for magnesium replacement.
Magnesium oxideDrug
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.
Magnesium glucoheptonateDrug
Magnesium glucoheptonate 30mL po q12h x 2 is an oral option for magnesium replacement in the higher-target arm.
| Study group | Role | What they receive |
|---|---|---|
| Lower target (>0.7mmol) | Other | 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. Receives: Drug: Magnesium sulfate administration |
| Higher target (>0.95mmol/L) | Other | 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. Receives: Drug: Magnesium sulfate administration; Drug: Magnesium oxide; Drug: Magnesium glucoheptonate |
What is being measured
The primary outcome is the main question the study is designed to answer.
30-day ordinal composite of hospital mortality and days free of atrial fibrillation in ICU
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.
Measured: 30 days after enrollment.
Secondary outcomes (18)
Organ-support free days
Number of days alive and free of invasive ventilation, vasopressors, and renal replacement therapy
Measured: 30 days
ICU-free days
Number of days alive and not in ICU
Measured: 30 days
Invasive ventilation-free days
Number of days alive and free of invasive ventilation
Measured: 30 days
Vasopressor-free days
Days alive and not receiving vasopressors
Measured: 30 days
Renal replacement therapy-free days
Days alive and not receiving renal replacement therapy in the ICU
Measured: 30 days
Ventricular arrhythmia
Binary outcome noting the occurence of either sustained ventricular tachycardia or ventricular fibrillation in ICU (1), or not (0).
Measured: 30 days
Intravenous antiarrhythmics
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.
Measured: 30 days
Magnesium and potassium levels in ICU
Daily levels of magnesium and potassium in ICU
Measured: 30 days
Magnesium administrations
Magnesium administrations while in ICU (number per day)
Measured: 30 days
Fluid balance
Daily fluid balance (sum of all liquid intakes minus the sum of all liquid outputs).
Measured: 30 days
DOOR 1: Death and arrhythmia
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.
Measured: 30 days
DOOR 2: Survival, organ dysfunction, hospitalization, discharge
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.
Measured: 30 days
Hospital mortality
Hospital mortality
Measured: 60 days
Hospital mortality
Hospital mortality
Measured: 90 days
Hospital length of stay
Length of hospitalization, including transfers within the health network.
Measured: 90 days
Discharge destination
Categorical variable noting discharge destination on index hospitalization (eg home, retirement home, long-term care, acute care hospital, etc).
Measured: 90 days
Magnesium administrations - by mass
Elemental magnesium administered (g per day)
Measured: 30 days
Magnesium administrations - route
Route of magnesium administrations each day (PO vs IV)
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2025
- Study start25 Nov 2025
- Primary completion1 Mar 2027 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Pragmatic comparative effectiveness trial
- Masking
- None (open label)
- Enrolment
- 3,853 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Scarborough General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Scarborough Health Network, Lakeridge Health Corporation
- Responsible party
- Principal investigator, Christopher Yarnell, Scarborough General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07173855
- Sponsor's protocol ID
- ICU-25-018
- Acronym
- MAGNOLIA
- Status last verified
- Sep 2025
- First submitted
- 8 Sep 2025
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified data will be posted in the Health Data Nexus (https://healthdatanexus.ai/) deidentified data repository overseen by the University of Toronto Temerty Centre for Artificial Intelligence Research and Education in Medicine. This will allow credentialed access to deidentified individual patient data.