Magnesium vs Amiodarone for Atrial Fibrillation

(MAGNAM Trial)

Recruiting at 4 trial locations

Overseen By Project Manager

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Sunnybrook Health Sciences Centre

Must not be taking: Digoxin, Anti-arrhythmics

Disqualifiers: Age <18, Pregnancy, Others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6-24 hours

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for fast atrial fibrillation (AF), a condition where the heart beats irregularly and too quickly. The researchers aim to determine if magnesium sulfate (a mineral supplement), followed by digoxin, is more effective than the usual treatment, amiodarone, in restoring a normal heart rhythm. Participants will be selected from hospital ICUs and must have a new and rapid AF episode. This trial suits those who have recently experienced rapid AF and are under continuous heart monitoring as part of their care. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you have not taken digoxin or certain heart rhythm medications in the last 24 hours. If you are on these medications, you may need to stop them before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that magnesium sulfate is usually well-tolerated. Studies indicate that receiving magnesium does not affect blood pressure, pulse, or heart rhythm. Patients who received magnesium often had a lower heart rate 24 hours after experiencing fast atrial fibrillation (an irregular and rapid heartbeat) compared to those who did not receive it.

Amiodarone, a common treatment for heart rhythm issues, has been shown to effectively stabilize heart rhythms, though it can sometimes cause side effects like low blood pressure or a slow heart rate.

Both treatments have been studied for their safety in humans, indicating they are considered safe enough for testing in the current trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using magnesium sulfate for treating atrial fibrillation because it offers a different approach compared to traditional medications like amiodarone. Magnesium sulfate acts as a first-line treatment and is followed by digoxin and then amiodarone, which could potentially streamline treatment steps. Unlike standard treatments that primarily focus on restoring heart rhythm, magnesium sulfate might provide a more immediate impact on heart rate control, offering a potentially faster and more efficient option. This new protocol could lead to quicker stabilization for patients experiencing fast atrial fibrillation.

What evidence suggests that this trial's treatments could be effective for atrial fibrillation?

Research has shown that magnesium sulfate, which participants in this trial may receive, can help control heart rate in people with atrial fibrillation (AF). Patients who received magnesium experienced a lower heart rate within 24 hours of an AF episode. A review of several studies suggests that administering magnesium through an IV, in doses from 1.2 to 10 grams, is both safe and effective for treating sudden AF. Meanwhile, amiodarone, used in the standard of care arm of this trial, is a well-known treatment for AF and often helps restore a normal heart rhythm. Both treatments are promising, but they manage AF in different ways. ^{1 4 6 7 8}

Who Is on the Research Team?

Brian Cuthbertson, MD

Principal Investigator

Sunnybrook Health Sciences Centre

Are You a Good Fit for This Trial?

The MAGNAM trial is for adults in critical care with a new or existing diagnosis of fast atrial fibrillation (heart rate over 120/min) who need medical treatment. They must be able to have heart monitoring and not have used certain heart medications recently, nor should they have specific heart conditions, be pregnant, or critically ill with life expectancy under 12 hours.

Inclusion Criteria

I have had a recent episode of fast heart rate over 120 beats per minute due to atrial fibrillation.

I can have heart monitoring as part of my care.

My doctor says I need treatment for my irregular heartbeat.

Exclusion Criteria

You have chosen to focus on comfort care, or are expected to pass away within the next 12 hours.

I have a history of serious heart rhythm problems without a pacemaker.

Your potassium levels are consistently too high, even with treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive 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

6-24 hours

Continuous monitoring in ICU

Follow-up

Participants are monitored for safety and effectiveness after treatment, including heart rate control and restoration of normal sinus rhythm

Up to 90 days

Regular assessments during ICU stay and at discharge

Long-term follow-up

Continuation of trial intervention and monitoring for secondary outcomes such as hospital mortality and serious adverse events

Up to 90 days

What Are the Treatments Tested in This Trial?

Interventions

• Amiodarone
• Digoxin
• Magnesium Sulfate

Trial Overview This study tests if high-dose Magnesium Sulfate followed by Digoxin can more effectively restore normal heart rhythm compared to Amiodarone in patients with rapid atrial fibrillation. It's a randomized controlled trial across multiple centers where patients are chosen at random to receive one of the treatments.

How Is the Trial Designed?

Group I: Experimental arm Experimental Treatment 1 Intervention

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

Group II: Standard of care arm Active Control 1 Intervention

Intravenous amiodarone as compactor group intervention

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Sunnybrook Research Institute

Collaborator

Trials

33

Recruited

216,000+

Published Research Related to This Trial

In a study of 42 critically ill patients with atrial tachyarrhythmias, intravenous magnesium sulfate was found to be more effective than amiodarone in converting patients to sinus rhythm over a 24-hour period.

Both magnesium sulfate and amiodarone were equally effective in initially slowing the ventricular response rate in patients who did not convert to sinus rhythm, indicating that while magnesium is superior for conversion, both treatments can help manage heart rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parenteral magnesium sulfate versus amiodarone in the therapy of atrial tachyarrhythmias: a prospective, randomized study. Moran, JL., Gallagher, J., Peake, SL., et al.[2019]

In a study of 29 critically ill patients with new-onset atrial fibrillation, magnesium sulfate (MgSO4) was effective in converting 16 patients to sinus rhythm, potentially reducing the need for the antiarrhythmic drug amiodarone.

The new treatment protocol, which involved an MgSO4 bolus followed by continuous infusion, achieved a 90% conversion rate to sinus rhythm within 24 hours, indicating both efficacy and safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of magnesium-amiodarone step-up scheme in critically ill patients with new-onset atrial fibrillation: a prospective observational study. Sleeswijk, ME., Tulleken, JE., Van Noord, T., et al.[2017]

In a clinical trial involving 48 patients with new-onset rapid atrial fibrillation, intravenous magnesium sulfate (MgSO4) did not show a significant difference in reducing heart rate compared to a saline placebo after 2 hours.

Both treatment groups experienced a decrease in heart rate, but the rate of decrease and the proportion of patients converting to normal sinus rhythm were similar, indicating that MgSO4 may not be effective for this condition in the emergency department setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnesium sulfate versus placebo for paroxysmal atrial fibrillation: a randomized clinical trial. Chu, K., Evans, R., Emerson, G., et al.[2015]

In a study of 97 patients with symptomatic atrial fibrillation (AF), the use of Magnesium Sulfate (MgSO4) alongside flecainide resulted in a higher cardioversion rate (91.3%) compared to those who did not receive MgSO4 (80.4%).

While the combination of MgSO4 and flecainide did not show statistically significant improvements, MgSO4 was associated with a lower heart rate at the time of cardioversion and had a high safety profile, suggesting it may help reduce the need for more aggressive treatments in the emergency department.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous Magnesium Sulfate Reduces the Need for Antiarrhythmics during Acute-Onset Atrial Fibrillation in Emergency and Critical Care. Gilardi, E., Pomero, F., Ravera, E., et al.[2022]

In a study involving 15 adults with newly recognized atrial fibrillation, parenteral magnesium sulfate (MgSO4) significantly reduced ventricular rates by 16% within 5 minutes, demonstrating its potential efficacy in acute management.

When combined with digoxin, the therapy showed a tendency for even greater rate control, suggesting that MgSO4 could be a valuable addition to treatment strategies for rapid ventricular rates in atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of magnesium sulfate on ventricular rate control in atrial fibrillation. Hays, JV., Gilman, JK., Rubal, BJ.[2019]

In a study of 438 patients undergoing lobectomy, both amiodarone and magnesium sulfate significantly reduced the incidence of atrial fibrillation (AF) compared to a control group, with amiodarone showing a slightly lower AF rate (10% vs. 12.5%).

Both medications also contributed to shorter intensive care unit and total hospital stays, indicating their effectiveness not only in preventing AF but also in improving overall recovery after lung surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study between amiodarone and magnesium sulfate as antiarrhythmic agents for prophylaxis against atrial fibrillation following lobectomy. Khalil, MA., Al-Agaty, AE., Ali, WG., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8691303/

The Role of Magnesium in the Management of Atrial ... Patients that received magnesium had a lower mean heart rate after 24 hours of the onset of the atrial fibrillation with RVR episode compared to the patients ...

2. aafp.org aafp.org/pubs/afp/issues/2009/0715/p157.html

Therapeutic Uses of Magnesium Results of a meta-analysis suggest that 1.2 to 10 g of intravenous magnesium sulfate is also a safe and effective strategy for the acute ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9598104/

The Role of Hypomagnesemia in Cardiac Arrhythmias Adjunctive therapy with magnesium showed to be helpful in further reducing the incidence of atrial fibrillation in patients with a magnesium ...

4. facebook.com facebook.com/EMNote.org/posts/intravenous-magnesium-sulfate-mgso4-appears-to-be-an-effective-adjunct-treatment/883780360455359/

Intravenous magnesium sulfate (MgSO4) appears to be an ... Trial evidence shows i.v. magnesium to be effective for controlling the ventricular response in patients with AF. Early investigations ...

5. academic.oup.com academic.oup.com/ehjcvp/article/3/2/108/2669829

Treating arrhythmias with adjunctive magnesium: identifying ... Trial evidence shows i.v. magnesium to be effective for controlling the ventricular response in patients with AF. Early investigations showed significant ...

6. arrhythmia.biomedcentral.com arrhythmia.biomedcentral.com/articles/10.1186/s42444-022-00065-z

Electrolyte's imbalance role in atrial fibrillation Calcium and magnesium could influence the risk of atrial fibrillation which is the leading cause of cardiac death, heart failure and ischemic stroke.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12324752/

The Effect of Continuous Magnesium Infusion to Prevent ... Postoperative continuous magnesium infusion after a bolus was effective in preventing POAF in patients undergoing OP-CABG by maintaining serum ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/0002870389904067

Effect of the infusion of magnesium sulfate during atrial ... Magnesium infusion did not affect blood pressure, pulse rate, PR or QRS or QT interval. Increasing the pacing frequency resulted in a statistically significant ...