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
- Are there results?
- Not yet: the study is under way
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.
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Protocolized Magnesium Replacement in Critically Ill Patients on Mortality and Atrial Fibrillation: the MAGNOLIA Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07173855
- Acronym / sponsor ID
- MAGNOLIA / ICU-25-018
- Conditions
- Critical Illness
- Keywords
- Critical illness, Magnesium, Atrial fibrillation, Protocols
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 3,853 participants (estimated)
- Lead sponsor
- Scarborough General HospitalUniversity, hospital or other
- Collaborators
- Scarborough Health Network, Lakeridge Health Corporation
- Study start
- 25 Nov 2025 (actual)
- Primary completion
- 1 Mar 2027 (estimated)
- Study completion
- 1 Jun 2027 (estimated)
- First posted
- 15 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Pragmatic comparative effectiveness trial
| Arm | Type | Receives |
|---|---|---|
| Lower target (>0.7mmol) | Other | Drug: Magnesium sulfate administrationProtocolized 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. |
| Higher target (>0.95mmol/L) | Other | Drug: Magnesium sulfate administration, Drug: Magnesium oxide, Drug: Magnesium glucoheptonateProtocolized 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. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Age 16 years or older
- Admission orders written to a medical-surgical intensive care unit at a participating site
- Magnesium replacement protocol ordered
Key exclusion criteria (4 listed)
- Prior enrollment in or withdrawal from MAGNOLIA trial
- Sustained ventricular tachycardia
- Pre-eclampsia
- Myasthenia gravis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Magnesium sulfate administrationMagnesium sulfate is used in both arms for magnesium replacement. | Drug | Higher target (>0.95mmol/L), Lower target (>0.7mmol) |
| Magnesium oxideIn 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. | Drug | Higher target (>0.95mmol/L) |
| Magnesium glucoheptonateMagnesium glucoheptonate 30mL po q12h x 2 is an oral option for magnesium replacement in the higher-target arm. | Drug | Higher target (>0.95mmol/L) |
Primary outcome
30-day ordinal composite of hospital mortality and days free of atrial fibrillation in ICU
Time frame: 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.
18 secondary outcomes
Organ-support free days
Time frame: 30 days
ICU-free days
Time frame: 30 days
Invasive ventilation-free days
Time frame: 30 days
Vasopressor-free days
Time frame: 30 days
Renal replacement therapy-free days
Time frame: 30 days
Ventricular arrhythmia
Time frame: 30 days
Intravenous antiarrhythmics
Time frame: 30 days
Magnesium and potassium levels in ICU
Time frame: 30 days
Magnesium administrations
Time frame: 30 days
Fluid balance
Time frame: 30 days
DOOR 1: Death and arrhythmia
Time frame: 30 days
DOOR 2: Survival, organ dysfunction, hospitalization, discharge
Time frame: 30 days
Hospital mortality
Time frame: 60 days
Hospital mortality
Time frame: 90 days
Hospital length of stay
Time frame: 90 days
Discharge destination
Time frame: 90 days
Magnesium administrations - by mass
Time frame: 30 days
Magnesium administrations - route
Time frame: 30 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Joshua Craig (4164382911 ext. 86006, jcraig@shn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
30-day ordinal composite of hospital mortality and days free of atrial fibrillation in ICU (time frame: 30 days after enrollment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2026.