MAGNAM Trial, Magnesium Versus Amiodarone in Atrial Fibrillation in Critical Care

NCT05287191 | Recruiting Phase 3

• 1 other identifier: 3664
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 5

Brief 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 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.

Conditions

Atrial Fibrillation New Onset

Keywords

Atrial fibrillation; critical illness

Outcome Measures

Primary Outcomes (2)

• Heart rate control (<110 beats per minute) and/or restoration of normal sinus

  heart rate control

  6 hours

• ICU free days

  ICU free days

  90 days

Secondary Outcomes (6)

• Hospital mortality

  Up to 90 days

• Heart rate

  24 hours

• Continuation of trial intervention

  Up to 90 days

• Presence of new rate and / or rhythm control medications at the time of first ICU discharge

  Up to 90 days

• Serious adverse events

  Up to 90 days

Study Arms (2)

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

Drug: Magnesium sulfate and then Digoxin

Standard of care arm

ACTIVE COMPARATOR

Intravenous amiodarone as compactor group intervention

Drug: Amiodarone

Interventions

Magnesium sulfate and then Digoxin DRUG

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.

Experimental arm

Amiodarone DRUG

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).

Standard of care arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Admitted to a participating hospital ICU
• A newly documented episode of fast Atrial Fibrillation with heart rate \>120/min confirmed by a 12-lead ECG assessment regardless of baseline rhythm (note- The AF can be acute or chronic diagnosis)
• Undergoing, or able to commence continuous electrocardiographic monitoring ("telemetry") as part of their routine clinical care
• Treating physician determines the patient has clinically significant AF that requires medical treatment

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Sunnybrook Research Institute: collaborator

Study Sites (5)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N3M5, Canada

RECRUITING

St Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

RECRUITING

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

RECRUITING

University Health Network - Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

University Health Network - Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

RECRUITING

MeSH Terms

Conditions

Atrial Fibrillation; Critical Illness

Interventions

Magnesium Sulfate; Amiodarone

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Magnesium Compounds; Inorganic Chemicals; Sulfates; Sulfuric Acids; Sulfur Acids; Sulfur Compounds; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Brian H Cuthbertson, MD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brian H Cuthbertson, MD

CONTACT

416 480 6100; brian.cuthbertson@sunnybrook.ca

Project Manager

CONTACT

MAGNAM@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Blinded follow up for key outcomes
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Individual patient, pragmatic, comparative effectiveness, randomised, controlled trial

Study Record Dates

• First Submitted: January 6, 2022
• First Posted: March 18, 2022
• Study Start: January 5, 2022
• Primary Completion: October 31, 2025
• Study Completion: April 30, 2026
• Last Updated: April 25, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 12 months after publication
• Access Criteria: Contact PI

Locations

CA (5)