Magnesium Sulfate for Atrial Fibrillation Prevention

(ATOMIC Trial)

Overseen By Miranda Hunt

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Dr. Stephanie Sibley

Must not be taking: Parenteral magnesium

Disqualifiers: Atrial fibrillation, Cardiac surgery, Dialysis, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 days

140 Participants Needed

Trial Summary

What is the purpose of this trial?

A double-blind, multi-centre, randomized, placebo-controlled, feasibility pilot trial in the prevention of new onset atrial fibrillation of critically ill patients admitted to an ICU.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug magnesium sulfate for preventing atrial fibrillation?

Research shows that magnesium sulfate can reduce the incidence of atrial fibrillation after coronary artery bypass surgery, which suggests it might help prevent atrial fibrillation in other situations too. ^{1 2 3 4 5}

Is magnesium sulfate safe for humans?

Magnesium sulfate is generally considered safe for humans, with studies showing it has negligible side effects when used as an antiarrhythmic agent (a treatment for irregular heartbeats) after heart surgery. ^{2 3 4 5 6}

How does the drug magnesium sulfate differ from other treatments for atrial fibrillation?

Magnesium sulfate is unique because it is used intravenously (directly into the vein) to help control the heart rate in atrial fibrillation, especially in cases where patients may have magnesium deficiency. It is noted for its rapid action and effectiveness in some cases where other drugs have failed, although its overall effect on heart rate control is limited. ^{1 2 5 7 8}

Research Team

Stephanie Sibley, MD

Principal Investigator

Queen's University

Eligibility Criteria

This trial is for adults over 18 in critical care needing breathing support or medication for shock. They must be receiving heart monitoring and expected to survive more than 24 hours. Pregnant women, those with current or past atrial fibrillation, patients post-cardiac surgery, on dialysis, or needing magnesium therapy cannot join.

Inclusion Criteria

I am in critical care needing breathing support or medication for shock.

I am 18 years old or older.

I am under continuous heart monitoring.

Exclusion Criteria

I was admitted to the ICU more than 12 hours ago.

You are not expected to live more than 24 hours, or you are receiving palliative care.

I have ongoing or occasional atrial fibrillation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either magnesium sulfate or placebo intravenously for a total of 10 doses

5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

Long-term follow-up

Participants are monitored for functional outcomes such as death after discharge

365 days

Treatment Details

Interventions

• Magnesium Sulfate
• Placebo

Trial Overview The study tests if magnesium sulfate can prevent new-onset atrial fibrillation in critically ill ICU patients compared to a placebo. It's a double-blind pilot trial meaning neither the participants nor the researchers know who receives the real treatment.

Participant Groups

Group I: Magnesium Sulfate Experimental Treatment 1 Intervention

4g Magnesium sulfate (100mL) BID, given intravenously over 2 hours, for a total of 10 doses

Group II: 0.9% NaCl Placebo Group 1 Intervention

100mL 0.9% NaCl BID, given intravenously over 2 hours, for a total of 10 doses

Magnesium Sulfate is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Magnesium sulfate for:

• Seizure prevention in pre-eclampsia
• Asthma exacerbation treatment
• Constipation treatment

Approved in European Union as Magnesium sulphate for:

• Pre-eclampsia and eclampsia treatment
• Hypomagnesemia treatment

Approved in Canada as Magnesium sulfate for:

• Seizure prevention in pre-eclampsia
• Asthma exacerbation treatment

Who Is Running the Clinical Trial?

Dr. Stephanie Sibley

Lead Sponsor

Trials

1

Recruited

140+

Dr. Stephanie Sibley

Lead Sponsor

Trials

1

Recruited

140+

Queen's University

Lead Sponsor

Trials

382

Recruited

122,000+

Southeastern Ontario Academic Medical Organization (SEAMO)

Collaborator

Trials

1

Recruited

140+

Findings from Research

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 167 coronary artery bypass patients, adding magnesium sulfate to propranolol did not significantly reduce the incidence of postoperative atrial fibrillation compared to propranolol alone, with rates of 22.4% and 19.5% respectively.

The combination of magnesium and propranolol led to more cases of postoperative hypotension, which complicated treatment and did not provide a clear benefit in preventing atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The combination of propranolol and magnesium does not prevent postoperative atrial fibrillation. Solomon, AJ., Berger, AK., Trivedi, KK., et al.[2019]

In a study of 234 patients undergoing coronary artery bypass grafting (CABG), those who received intravenous magnesium sulfate had a significantly lower incidence of postoperative atrial fibrillation (AF) compared to those who did not receive the treatment (p = 0.038).

While magnesium sulfate reduced the occurrence of AF after surgery, it did not affect the number of patients discharged with AF, and patients who experienced AF had a higher likelihood of longer hospital stays (p = 0.036).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnesium sulfate for prevention of postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting. Brackbill, ML., Moberg, L.[2019]

In a study of 88 patients undergoing elective coronary artery bypass grafting (CABG), magnesium sulfate (MgSO4) was found to be safe and effective in reducing the incidence of atrial fibrillation (AF) post-surgery, with no significant complications related to its use.

Both high (10 gm) and low (5 gm) doses of MgSO4 showed similar effectiveness in preventing AF, suggesting that the lower dose is sufficient and may help avoid potential adverse effects associated with higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnesium Sulfate Reduces Incidence of Atrial Fibrillation after Coronary Arterial Bypass Surgery: What Is the Proper Dose? A Randomized Trial. Taksaudom, N., Cheewinmethasiri, J., Chittawatanarat, K., et al.[2018]

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 100 patients with arrhythmias after cardiac surgery, magnesium sulfate was found to be an effective antiarrhythmic agent, showing a 56% effectiveness rate compared to 74% for standard agents like lidocaine and amiodarone, although this difference was not statistically significant.

Magnesium sulfate was particularly more effective in patients with low magnesium levels and in cases of ventricular arrhythmias, suggesting its potential as a first-line treatment without the need for routine blood level monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiarrhythmic effect of magnesium sulfate after open heart surgery: effect of blood levels. Kiziltepe, U., Eyileten, ZB., Sirlak, M., et al.[2019]

Intravenous magnesium sulfate (MgSO4) significantly reduced the ventricular rate in patients with rapid atrial fibrillation, showing a notable decrease at 15, 30, and 60 minutes after administration.

The effectiveness of MgSO4 did not vary between magnesium deficient and nondeficient patients, indicating that magnesium levels do not influence the response to this treatment in the context of rapid atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnesium efficacy in magnesium deficient and nondeficient patients with rapid ventricular response atrial fibrillation. Eray, O., Akça, S., Pekdemir, M., et al.[2020]

Intravenous magnesium sulfate was successfully used to treat tachyarrhythmias in four patients, demonstrating rapid efficacy and no adverse reactions, particularly in cases resistant to other treatments.

The treatment was effective for different types of tachyarrhythmias, including supraventricular tachycardia and torsade de pointes, suggesting that magnesium sulfate could be a valuable option for patients with magnesium depletion or resistant arrhythmias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic effectiveness of intravenous magnesium sulfate in tachyarrhythmia. Apropos of 4 clinical cases]. Rabaçal, C., Pereira, D., Carvalho, E., et al.[2006]

References

1. United States pubmed.ncbi.nlm.nih.gov

Effect of magnesium sulfate on ventricular rate control in atrial fibrillation. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

The combination of propranolol and magnesium does not prevent postoperative atrial fibrillation. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Magnesium sulfate for prevention of postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting. [2019]

4. Thailand pubmed.ncbi.nlm.nih.gov

Magnesium Sulfate Reduces Incidence of Atrial Fibrillation after Coronary Arterial Bypass Surgery: What Is the Proper Dose? A Randomized Trial. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Magnesium sulfate versus placebo for paroxysmal atrial fibrillation: a randomized clinical trial. [2015]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Antiarrhythmic effect of magnesium sulfate after open heart surgery: effect of blood levels. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Magnesium efficacy in magnesium deficient and nondeficient patients with rapid ventricular response atrial fibrillation. [2020]

8. Portugal pubmed.ncbi.nlm.nih.gov

[Therapeutic effectiveness of intravenous magnesium sulfate in tachyarrhythmia. Apropos of 4 clinical cases]. [2006]