Atrial Fibrillation New OnsetPhase 3MAGNAMNCT05287191
MAGNAM Trial, Magnesium Versus Amiodarone in Atrial Fibrillation in Critical Care
A Phase 3 study testing Magnesium sulfate and then Digoxin and Amiodarone in people with Atrial Fibrillation New Onset, run by Sunnybrook Health Sciences Centre at 5 sites in Canada.
Trial summary
A multi-centre, non-blinded, comparative effectiveness, randomised controlled trial. Patients will be prospectively enrolled from Critical Care Units and will be assessed for study enrollment based on inclusion/exclusion criteria at the time of the onset of fast atrial fibrillation (AF)(irregular and often rapid heart… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation New Onset
- What is being tested?
- Magnesium sulfate and then Digoxin and Amiodarone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 5 sitesCanada
- Study dates
- 5 Jan 2022to 30 Apr 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Age <18 years
- Palliative goals of care or expected to die in the next 12 hours
- Fast Atrial Fibrillation (>120/min) present for > 48 hours
- Treatment with digoxin or a class I or III anti-arrhythmic medication within the preceding 24 hours
- MgSO4 dose of > 3g IV in the last 2 hours.
- History of high grade Atrio-Ventricular conduction block or bradyarrhythmia without pacemaker
Show all 14Show fewer
- Non-cardiac indication or contraindication to one of the study treatments (hypertensive disorders of pregnancy, pre-term labour, neuromuscular junction disorders i.e. known Myasthenia gravis; documented prior history of amiodarone toxicity or relative contraindication such as thyroid disease, cirrhosis, pulmonary fibrosis, etc.)
- Recent cardiac surgery during index hospital admission
- Known pregnancy
- Sustained (more than 10 continuous seconds documented on a rhythm strip) ventricular arrhythmia within the past 24 hours
- Known or suspected pre-excitation syndrome
- Persistent hyperkalemia > 6mmol/l despite treatment
- Previously enrolled in the MAGNAM trial
- Recent lung transplantation (during this admission)
Trial locations and contacts
5 sites in 1 country.
Project Manager contact
5 sites in 1 country
Canada5 sites, 5 recruiting
- Recruiting
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N3M5
Project Manager, MAGNAM@sunnybrook.ca
Brian Cuthbertson, MD
- Recruiting
St Michael's Hospital
Toronto, Ontario, M5B 1W8
Marlene Santos, Marlene.Santos@unityhealth.to
Jan Friedrich, MD
- Recruiting
Mount Sinai Hospital
Toronto, Ontario, M5G 1X5
Jenna Spring, MD, Jenna.Spring@sinaihealth.ca
Jenna Spring, MD
- Recruiting
University Health Network - Toronto General Hospital
Toronto, Ontario, M5G 2C4
David McAlpine, MD, David.McAlpine@uhn.ca
Eddy Fan, MD
- Recruiting
University Health Network - Toronto Western Hospital
Toronto, Ontario, M5T 2S8
Bourke Tillmann, BourkeWilliam.Tillmann@uhn.ca
Bourke Tillmann, MD
About this study
Official title: MAGNesium and Digoxin Versus AMiodarone for Fast Atrial Fibrillation in the ICU (MAGNAM Trial)
A multi-centre, non-blinded, comparative effectiveness, randomised controlled trial. Patients will be prospectively enrolled from Critical Care Units and will be assessed for study enrollment based on inclusion/exclusion criteria at the time of the onset of fast atrial fibrillation (AF)(irregular and often rapid heart rate). The authors hypothesize that high dose Magnesium Sulphate with the addition of Digoxin as a second line treatment will improve the success rate in returning the heart to normal rhythm as well as speed of resolution of critical illness in new onset rapid atrial fibrillation in the critically ill cared for in general ICUs.
Read the detailed description
This is a Multi-centre, randomised controlled, clinical trial that is comparing a Stepwise Strategy of Magnesium Followed by Digoxin, With an Amiodarone Backup vs a Strategy of First-line Amiodarone to See Which is More Effective in Returning the Heart to Normal Rhythm After Experiencing Rapid Atrial Fibrillation in General ICUs. It will take place in Critical Care Units in Toronto Health Sciences Centres over a course of 2 years. The sample size is 200 patients.
Investigational Product and Planned Use Magnesium sulphate
The trial intervention will be Magnesium sulphate followed by digoxin as second line therapy with Amiodarone as third line. The Standard of care intervention will be Amiodarone as first line treatment in the and then no more than 2g MgSO4 be delivered.
Data will be collected retrospectively at the outcome timepoints.
Statistical Analysis:
This analysis will be conducted using the intention to treat principle, therefore all randomised patients will be included in the main analysis. Crossovers and protocol violations will remain in their original study group.
Baseline data will be summarized per group for continuous variables using means and standard deviations or medians and interquartile ranges as indicated the distribution and for discrete variables using frequencies and percentages. For the rate / rhythm co-primary outcome the authors will use a sentinel time point analysis at the 6 and 24 hour time points assuming there no / very low competing risk for death using a multivariate regression model to test for differences between groups and adjusting for baseline variables such as age, hospital site, shock status (requirement for inotropes Y/N), mechanical ventilation (Y/N) and known chronic atrial fibrillation. For the ICU length of stay co-primary outcome the authors recognise the competing risk of death and for this outcome and the authors propose to use Fine and Gray models adjusting for the stratification variables (as above). Estimates will be presented as sub-distribution hazards and 95% confidence intervals. The authors will test for interaction between sub-group and treatment and present the estimates per sub-group.
All secondary outcomes are binary and differences between groups will be tested using Chi square test or Fisher exact test as appropriate. Missing data will be uncommon for our key outcome data considering the nature of this data. The authors do not propose to use imputation for missing data in these primary or secondary analyses.
- Conditions
- Atrial Fibrillation New Onset
- Being tested
- Magnesium sulfate and then Digoxin, Amiodarone
- Keywords
- Atrial fibrillation, critical illness
- Medical subject headings
- Atrial Fibrillation, Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnesium sulfate and then DigoxinDrug
We will test MgSO4 and then digoxin IV (in 3 divided dose) as second line therapy with amiodarone IV as third line. Digoxin will be protocolised to commence between 30 minutes and 12 hours after MgSO4 if fast Atrial Fibrillation persists as initially designated (dose 1). Undiluted IV digoxin (12 mcg/kg) will be administered in 3 divided doses (6, 3 and 3 mcg/kg) separated by approximately 6 hrs (i.e. dose 1 at 30 mins - 12 hours after MgSO4, followed by dose 2 at -6 hrs and dose 3 at the approximately 12 hrs). Patients with renal dysfunction (creatinine clearance <60 ml/min measured by the Modification of diet in renal disease formula) will receive a reduced dose of 8 mcg/kg in 3 divided doses (4, 2, and 2 mcg/kg) separated by the same time intervals. In the trial intervention group, amiodarone will be given approximately 120 mins after digoxin if necessary whilst completing the digoxin dose. Amiodarone as a 150 mg infusion over 10 minutes followed by 900 mg over 24 hours.
AmiodaroneDrug
We will test Amiodarone (150mg IV then 900mg IV over the next 24 hours ) as first line treatment in the standard of care group. No more than 2g MgSO4 be delivered over 2 hours maximum for this group in the first 24 hours after randomisation unless clinically indicated for measured hypomagnesaemia (a value below the index hospital laboratories lower limit of normal).
| Study group | Role | What they receive |
|---|---|---|
| Experimental arm | Experimental | Intravenous magnesium sulphate as first line followed by digoxin IV loading as second line and then amiodarone IV as third line treatments for fast Atrial Fibrillation Receives: Drug: Magnesium sulfate and then Digoxin |
| Standard of care arm | Active comparator | Intravenous amiodarone as compactor group intervention Receives: Drug: Amiodarone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heart rate control (<110 beats per minute) and/or restoration of normal sinus
heart rate control
Measured: 6 hours
ICU free days
ICU free days
Measured: 90 days
Secondary outcomes (6)
Hospital mortality
Hospital mortality
Measured: Up to 90 days
Heart rate
Maintenance rate control
Measured: 24 hours
Continuation of trial intervention
Continuation of any of the drugs in the intervention (magnesium, digoxin or amiodarone) at the time of discharge from ICU
Measured: Up to 90 days
Presence of new rate and / or rhythm control medications at the time of first ICU discharge
Presence of new rate and / or rhythm control medications
Measured: Up to 90 days
Serious adverse events
Serious adverse events
Measured: Up to 90 days
Avoidance of amiodarone
Avoidance of amiodarone during the ICU admission
Measured: Up to 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2022
- Study start5 Jan 2022
- Primary completion31 Oct 2025 (estimated)
- Study completion30 Apr 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial Fibrillation New OnsetStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Individual patient, pragmatic, comparative effectiveness, randomised, controlled trial
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Sunnybrook Research Institute
- Responsible party
- Sponsor
- Investigators
- Brian H Cuthbertson, MD, Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05287191
- Sponsor's protocol ID
- 3664
- Acronym
- MAGNAM
- Status last verified
- Apr 2024
- First submitted
- 6 Jan 2022
- Last updated
- 25 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Blinded data will be shared with other researchers after verification of their study plan and discussion about recognitions
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MAGNesium and Digoxin Versus AMiodarone for Fast Atrial Fibrillation in the ICU (MAGNAM Trial)
- ClinicalTrials.gov ID
- NCT05287191
- Acronym / sponsor ID
- MAGNAM / 3664
- Conditions
- Atrial Fibrillation New Onset
- Keywords
- Atrial fibrillation, critical illness
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Collaborators
- Sunnybrook Research Institute
- Study start
- 5 Jan 2022 (actual)
- Primary completion
- 31 Oct 2025 (estimated)
- Study completion
- 30 Apr 2026 (estimated)
- First posted
- 18 Mar 2022 (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.
A multi-centre, non-blinded, comparative effectiveness, randomised controlled trial. Patients will be prospectively enrolled from Critical Care Units and will be assessed for study enrollment based on inclusion/exclusion criteria at the time of the onset of fast atrial fibrillation (AF)(irregular and often rapid heart rate). The authors hypothesize that high dose Magnesium Sulphate with the addition of Digoxin as a second line treatment will improve the success rate in returning the heart to normal rhythm as well as speed of resolution of critical illness in new onset rapid atrial fibrillation in the critically ill cared for in general ICUs.
Detailed description
This is a Multi-centre, randomised controlled, clinical trial that is comparing a Stepwise Strategy of Magnesium Followed by Digoxin, With an Amiodarone Backup vs a Strategy of First-line Amiodarone to See Which is More Effective in Returning the Heart to Normal Rhythm After Experiencing Rapid Atrial Fibrillation in General ICUs. It will take place in Critical Care Units in Toronto Health Sciences Centres over a course of 2 years. The sample size is 200 patients.
Investigational Product and Planned Use Magnesium sulphate
The trial intervention will be Magnesium sulphate followed by digoxin as second line therapy with Amiodarone as third line. The Standard of care intervention will be Amiodarone as first line treatment in the and then no more than 2g MgSO4 be delivered.
Data will be collected retrospectively at the outcome timepoints.
Statistical Analysis:
This analysis will be conducted using the intention to treat principle, therefore all randomised patients will be included in the main analysis. Crossovers and protocol violations will remain in their original study group.
Baseline data will be summarized per group for continuous variables using means and standard deviations or medians and interquartile ranges as indicated the distribution and for discrete variables using frequencies and percentages. For the rate / rhythm co-primary outcome the authors will use a sentinel time point analysis at the 6 and 24 hour time points assuming there no / very low competing risk for death using a multivariate regression model to test for differences between groups and adjusting for baseline variables such as age, hospital site, shock status (requirement for inotropes Y/N), mechanical ventilation (Y/N) and known chronic atrial fibrillation. For the ICU length of stay co-primary outcome the authors recognise the competing risk of death and for this outcome and the authors propose to use Fine and Gray models adjusting for the stratification variables (as above). Estimates will be presented as sub-distribution hazards and 95% confidence intervals. The authors will test for interaction between sub-group and treatment and present the estimates per sub-group.
All secondary outcomes are binary and differences between groups will be tested using Chi square test or Fisher exact test as appropriate. Missing data will be uncommon for our key outcome data considering the nature of this data. The authors do not propose to use imputation for missing data in these primary or secondary analyses.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Individual patient, pragmatic, comparative effectiveness, randomised, controlled trial
| Arm | Type | Receives |
|---|---|---|
| Experimental arm | Experimental | Drug: Magnesium sulfate and then DigoxinIntravenous magnesium sulphate as first line followed by digoxin IV loading as second line and then amiodarone IV as third line treatments for fast Atrial Fibrillation |
| Standard of care arm | Active comparator | Drug: AmiodaroneIntravenous amiodarone as compactor group intervention |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (14 listed)
- Age <18 years
- Palliative goals of care or expected to die in the next 12 hours
- Fast Atrial Fibrillation (>120/min) present for > 48 hours
- Treatment with digoxin or a class I or III anti-arrhythmic medication within the preceding 24 hours
- MgSO4 dose of > 3g IV in the last 2 hours.
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 and then DigoxinWe will test MgSO4 and then digoxin IV (in 3 divided dose) as second line therapy with amiodarone IV as third line. Digoxin will be protocolised to commence between 30 minutes and 12 hours after MgSO4 if fast Atrial Fibrillation persists as initially designated (dose 1). Undiluted IV digoxin (12 mcg/kg) will be administered in 3 divided doses (6, 3 and 3 mcg/kg) separated by approximately 6 hrs (i.e. dose 1 at 30 mins - 12 hours after MgSO4, followed by dose 2 at -6 hrs and dose 3 at the approximately 12 hrs). Patients with renal dysfunction (creatinine clearance <60 ml/min measured by the Modification of diet in renal disease formula) will receive a reduced dose of 8 mcg/kg in 3 divided doses (4, 2, and 2 mcg/kg) separated by the same time intervals. In the trial intervention group, amiodarone will be given approximately 120 mins after digoxin if necessary whilst completing the digoxin dose. Amiodarone as a 150 mg infusion over 10 minutes followed by 900 mg over 24 hours. | Drug | Experimental arm |
| AmiodaroneWe will test Amiodarone (150mg IV then 900mg IV over the next 24 hours ) as first line treatment in the standard of care group. No more than 2g MgSO4 be delivered over 2 hours maximum for this group in the first 24 hours after randomisation unless clinically indicated for measured hypomagnesaemia (a value below the index hospital laboratories lower limit of normal). | Drug | Standard of care arm |
Primary outcome
Heart rate control (<110 beats per minute) and/or restoration of normal sinus
Time frame: 6 hours
heart rate control
ICU free days
Time frame: 90 days
ICU free days
6 secondary outcomes
Hospital mortality
Time frame: Up to 90 days
Heart rate
Time frame: 24 hours
Continuation of trial intervention
Time frame: Up to 90 days
Presence of new rate and / or rhythm control medications at the time of first ICU discharge
Time frame: Up to 90 days
Serious adverse events
Time frame: Up to 90 days
Avoidance of amiodarone
Time frame: Up to 90 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2024.
- Individual participant dataSharing planned: Yes. Blinded data will be shared with other researchers after verification of their study plan and discussion about recognitions
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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. This study is not recruiting at the moment.
Project Manager contact
Brian H Cuthbertson, MD principal investigator
Sunnybrook Health Sciences Centre
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Magnesium sulfate and then Digoxin and Amiodarone in people with Atrial Fibrillation New Onset, run by Sunnybrook Health Sciences Centre at 5 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 0 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 25 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Brian H Cuthbertson, MD (416 480 6100 ext. 2895, brian.cuthbertson@sunnybrook.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Heart rate control (<110 beats per minute) and/or restoration of normal sinus (time frame: 6 hours). The study lists 2 primary outcomes in all. 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 25 Apr 2024.