Magnesium Sulfate for Rapid Heartbeat

(ATRIUM Trial)

Overseen By Marc McDowell, PharmD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Aurora Health Care

Must be taking: Diltiazem

Disqualifiers: Renal disease, Heart failure, Pregnancy, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: 2 hours

153 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of magnesium sulfate for treating rapid heartbeat in atrial fibrillation with rapid ventricular response (AFF RVR). Participants will receive varying doses of magnesium sulfate or a placebo (a substance with no active treatment) to determine the most effective option. Individuals diagnosed with AFF RVR and experiencing a heart rate of 120 beats per minute or higher may qualify for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that you are on diltiazem for heart rate control.

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

Research has shown that magnesium sulfate is generally safe when used in the right amounts. It often treats conditions like seizures during pregnancy and low magnesium levels, indicating that the body usually handles it well. However, excessive intake can cause serious side effects. Previous studies found that these side effects can include nausea, low blood pressure, and skin flushing. Following dosing guidelines is important to reduce risks. This trial tests different doses, focusing on safety and tolerance. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using magnesium sulfate for treating rapid heartbeat because it offers a potentially faster and safer option compared to standard treatments like beta-blockers or calcium channel blockers. Magnesium sulfate works by stabilizing the electrical activity of the heart, which is different from how current medications generally work. This approach could lead to quicker relief from symptoms and fewer side effects. Additionally, the treatment is administered intravenously, allowing for rapid action, which is crucial for patients experiencing acute episodes of rapid heartbeat.

What evidence suggests that magnesium sulfate might be an effective treatment for rapid heartbeat?

Research shows that magnesium sulfate can help manage certain irregular heartbeats. In this trial, participants will receive either magnesium sulfate or a placebo. Studies have found that administering magnesium through an IV can lower pulse rates when combined with other medications for acute atrial fibrillation, a fast heartbeat condition. Magnesium has also been shown to reduce heart rate and improve heart function in various heart issues. Early research suggests that magnesium might lower the risk of early death in heart attack cases by helping the heart muscles relax. These findings suggest that magnesium sulfate could be beneficial for treating rapid heartbeat conditions. ^{6 7 8 9 10}

Who Is on the Research Team?

Travis Hase, MD

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for individuals with a type of irregular heartbeat known as atrial fibrillation/flutter and rapid heart rate. Specific eligibility criteria are not provided, but typically participants must meet certain health standards to be included.

Inclusion Criteria

I am taking Diltiazem for heart rate control.

Primary diagnosis AFF RVR greater than or equal to 120 bpm

English speaking

Exclusion Criteria

Withdrew from study

Impaired consciousness

Previously enrolled in this trial during a different patient encounter

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive intravenous magnesium or placebo to evaluate safety and efficacy in treating AFF RVR

2 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including heart rate changes and adverse effects

24 hours

What Are the Treatments Tested in This Trial?

Interventions

• Magnesium Sulfate

Trial Overview The study is testing the effects of two different doses of intravenous magnesium (2g and 4g) compared to a saline placebo in managing atrial fibrillation with a rapid ventricular response. It's set up so neither the patients nor the doctors know who gets which treatment.

How Is the Trial Designed?

Group I: Experimental Arm Two, Magnesium Sulfate 4g Experimental Treatment 1 Intervention

Magnesium Sulfate 4g/50ml 0.9% NaCl

Group II: Experimental Arm One, Magnesium Sulfate 2g Experimental Treatment 1 Intervention

Study drug (Magnesium Sulfate 2 gram/50ml 0.9% NaCl)

Group III: Control Arm, normal saline Placebo Group 1 Intervention

50ml 0.9% NaCl

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?

Aurora Health Care

Lead Sponsor

Trials

46

Recruited

16,400+

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Published Research Related to This Trial

In a study of eight normomagnesemic patients, intravenous magnesium sulfate (MgSO4) significantly increased serum magnesium levels and prolonged key ECG intervals, indicating its potential to affect heart conduction.

The observed prolongation of the PR interval and other conduction times suggests that magnesium may help treat certain arrhythmias by blocking slow sodium channels, although it did not significantly impact other cardiac conduction parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrophysiologic effects of intravenous magnesium in patients with normal conduction systems and no clinical evidence of significant cardiac disease. Kulick, DL., Hong, R., Ryzen, E., et al.[2019]

Magnesium sulfate (MgSO4) treatment in obstetrics has been associated with negative effects on the fetus and newborn, raising concerns about its safety in these populations.

There are conflicting reports regarding the tocolytic efficacy of magnesium sulfate, meaning its effectiveness in stopping preterm labor is still debated among researchers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficiency and safety of magnesium sulfate treatment in obstetrics]. Mikołajek, W., Chlubek, D.[2017]

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]

Magnesium sulphate has been successfully used as an antiarrhythmic agent in three different patients with arrhythmias affecting their heart function, demonstrating its versatility beyond just treating torsade de pointe.

The cases highlight that magnesium sulphate can effectively treat both ventricular arrhythmias and serve as a second-line treatment for supraventricular arrhythmias, suggesting its potential broader application in various arrhythmic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiarrhythmic effects of magnesium sulphate. Report of three cases. Knudsen, K., Abrahamsson, J.[2019]

A review of 59 studies involving 21,149 eclamptic women found that a significant number (25%) had normal blood pressure or mild-to-moderate hypertension before experiencing seizures, suggesting that eclampsia can occur even without severe hypertension.

The findings support the idea of administering magnesium sulfate prophylactically to all women with mild pre-eclampsia, as many women showed symptoms like headaches and visual disturbances prior to convulsions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Should magnesium sulfate be administered to women with mild pre-eclampsia? A systematic review of published reports on eclampsia. Berhan, Y., Berhan, A.[2022]

Magnesium sulfate infusion can be an effective treatment for certain types of cardiac dysrhythmias, as demonstrated in a case where a 38-year-old firefighter's atrial tachycardia was successfully converted to normal sinus rhythm after unsuccessful treatment with IV adenosine.

The administration of 2 g of magnesium sulfate over 5 minutes led to complete resolution of the patient's symptoms, suggesting its potential as a rapid intervention for managing supraventricular tachycardia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnesium sulfate for conversion of supraventricular tachycardia refractory to intravenous adenosine. LeDuc, TJ., Carr, JD.[2019]

Magnesium sulphate was found to be effective in managing ventricular arrhythmias in 28 patients with heart failure undergoing digitalis therapy, allowing continued digitalis treatment until cardiac function improved.

The study suggests that magnesium sulphate's anti-arrhythmic properties help mitigate the complications of digitalis therapy, although the specific mechanism of action in this context is explored further in the paper.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Anti-arrhythmic effect of magnesium cations. Protection against ventricular excitability during cardiotonic therapy]. Critelli, G., Ferro, G., Adinolfi, L., et al.[2013]

A 73-year-old man experienced an iatrogenic overdose of magnesium sulfate during treatment for suspected acute myocardial infarction, leading to serious side effects like bradycardia, hypotension, and apnea.

This case highlights the need for better education among emergency department staff regarding proper dosing and potential adverse effects of magnesium sulfate, especially since such overdoses in cardiac patients have not been previously reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iatrogenic magnesium overdose in a patient with suspected acute myocardial infarction. Frohna, WJ.[2012]

Magnesium therapy has been shown to be effective in treating intractable ventricular tachycardia and ventricular fibrillation, even in patients with normal magnesium levels, as well as in cases of 'torsades de pointes' and digoxin intoxication.

Parenteral magnesium sulfate administration was found to be safe and effective for controlling ventricular rates in multifocal atrial tachycardia, with specific dosing guidelines provided for patients without renal failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnesium and cardiac arrhythmias. Iseri, LT.[2013]

Magnesium sulfate treatment was effective in terminating various types of supraventricular tachyarrhythmias (SVTA) in a study of 25 cases, with significant improvements observed in conditions like paroxysmal supraventricular tachycardia (PSVT) and chaotic atrial tachycardia (CAT).

The treatment showed rapid effects, with many patients experiencing recovery within hours to days after intravenous infusion, indicating magnesium sulfate's potential as a safe and effective intervention for managing SVTA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical effects of magnesium sulfate in the treatment of supraventricular tachyarrhythmia]. Shao, M.[2016]

Citations

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

The Role of Hypomagnesemia in Cardiac Arrhythmias Magnesium sulphate administration decreases the reinitiation of torsade de pointes or other ventricular tachycardia rather than converting the ...

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

Treating arrhythmias with adjunctive magnesium: identifying ... Early investigations showed significant reductions in pulse rates when i.v. magnesium was used in combination with digoxin for managing acute AF.88,89 A trial ...

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

Therapeutic Uses of Magnesium Studies have shown the effectiveness of magnesium in eclampsia and preeclampsia, arrhythmia, severe asthma, and migraine.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/014067369291828V

Intravenous magnesium sulphate in suspected acute ... Several small clinical trials in suspected acute myocardial infarction have suggested that early mortality can be reduced by intravenous infusion of magnesium ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9389857/

Effects of magnesium sulphate on the cardiovascular ... MgSO4 produced dose-dependent decreases in arterial pressure, heart rate, left ventricular dP/dtmax and left ventricular minute work index (LVMWI).

6. drugs.com drugs.com/mtm/magnesium-sulfate.html

Magnesium sulfate Uses, Side Effects & Warnings Using too much magnesium sulfate can cause serious, life-threatening side effects. Do not use magnesium sulfate as a laxative without medical ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/magnesium-sulfate-oral-route-topical-application-route-route-not-applicable/description/drg-20088513

Magnesium sulfate (oral route, topical application ... Magnesium sulfate is used for short-term relief of constipation. It is also used as a soaking solution to relieve minor sprains, bruises, muscle aches or ...

8. drugs.com drugs.com/sfx/epsom-salt-side-effects.html

Epsom Salt Side Effects: Common, Severe, Long Term Learn about the side effects of Epsom Salt (magnesium sulfate), from common to rare, for consumers and healthcare professionals.

9. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK554553/

Magnesium Sulfate - StatPearls - NCBI Bookshelf Magnesium sulfate is a medication used to manage and treat multiple clinical conditions and holds several on and off-label uses.

10. go.drugbank.com go.drugbank.com/drugs/DB00653

Magnesium sulfate: Uses, Interactions, Mechanism of Action Magnesium sulfate is a drug used to treat convulsions during pregnancy, nephritis in children, magnesium deficiency, and tetany.