Clinical trial NCT05287191: MAGNAM Trial, Magnesium Versus Amiodarone in Atrial Fibrillation in Critical Care
Official title: MAGNesium and Digoxin Versus AMiodarone for Fast Atrial Fibrillation in the ICU (MAGNAM Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Atrial Fibrillation New Onset
Keywords: Atrial fibrillation
critical illness
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: Sunnybrook Research Institute
First posted: 2022-03-18
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Individual patient, pragmatic, comparative effectiveness, randomised, controlled trial
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria: Each participant must meet all of the following inclusion criteria to participate in this study:

1. Admitted to a participating hospital ICU
2. 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)
3. Undergoing, or able to commence continuous electrocardiographic monitoring ("telemetry") as part of their routine clinical care
4. Treating physician determines the patient has clinically significant AF that requires medical treatment

Exclusion Criteria:

1. Age \<18 years
2. Palliative goals of care or expected to die in the next 12 hours
3. Fast Atrial Fibrillation (\>120/min) present for \> 48 hours
4. Treatment with digoxin or a class I or III anti-arrhythmic medication within the preceding 24 hours
5. MgSO4 dose of \> 3g IV in the last 2 hours.
6. History of high grade Atrio-Ventricular conduction block or bradyarrhythmia without pacemaker
7. 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.)
8. Recent cardiac surgery during index hospital admission
9. Known pregnancy
10. Sustained (more than 10 continuous seconds documented on a rhythm strip) ventricular arrhythmia within the past 24 hours
11. Known or suspected pre-excitation syndrome
12. Persistent hyperkalemia \> 6mmol/l despite treatment
13. Previously enrolled in the MAGNAM trial
14. Recent lung transplantation (during this admission)

Primary outcomes:
measure: Heart rate control (<110 beats per minute) and/or restoration of normal sinus
timeFrame: 6 hours
measure: ICU free days
timeFrame: 90 days
Secondary outcomes:
measure: Hospital mortality
timeFrame: Up to 90 days
measure: Heart rate
timeFrame: 24 hours
measure: Continuation of trial intervention
timeFrame: Up to 90 days
measure: Presence of new rate and / or rhythm control medications at the time of first ICU discharge
timeFrame: Up to 90 days
measure: Serious adverse events
timeFrame: Up to 90 days
measure: Avoidance of amiodarone
timeFrame: Up to 90 days
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: St Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network - Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network - Toronto Western Hospital
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: Brian H Cuthbertson, MD
role: PRINCIPAL_INVESTIGATOR
References: