Atrial Fibrillation New Onset
Conditions
Keywords
Atrial fibrillation, critical illness
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.
Interventions
DRUGMagnesium sulfate and then Digoxin
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.
DRUGAmiodarone
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).
Sponsors
Sunnybrook Research Institute
Sunnybrook Health Sciences Centre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Blinded follow up for key outcomes
Intervention model description
Individual patient, pragmatic, comparative effectiveness, randomised, controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Heart rate control (<110 beats per minute) and/or restoration of normal sinus | 6 hours | heart rate control |
| ICU free days | 90 days | ICU free days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Continuation of trial intervention | Up to 90 days | Continuation of any of the drugs in the intervention (magnesium, digoxin or amiodarone) at the time of discharge from ICU |
| Presence of new rate and / or rhythm control medications at the time of first ICU discharge | Up to 90 days | Presence of new rate and / or rhythm control medications |
| Hospital mortality | Up to 90 days | Hospital mortality |
| Avoidance of amiodarone | Up to 90 days | Avoidance of amiodarone during the ICU admission |
| Serious adverse events | Up to 90 days | Serious adverse events |
| Heart rate | 24 hours | Maintenance rate control |
Countries
Canada
Contacts
Primary ContactBrian H Cuthbertson, MD
Backup ContactProject Manager
Outcome results
None listed