Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001076763
Ethics application status
Approved
Date submitted
21/07/2022
Date registered
4/08/2022
Date last updated
17/02/2023
Date data sharing statement initially provided
4/08/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessment of Magnesium administration effect on Atrial Fibrillation duration in patients admitted to the Intensive Care Unit.
Scientific title
A multi-centre, cluster, cross-over pilot study comparing efficacy of magnesium administration on the duration of early atrial fibrillation in intensive care patients requiring vasoactive drug support.
Secondary ID [1] 307632 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial Fibrillation 327123 0
Condition category
Condition code
Cardiovascular 324265 324265 0 0
Other cardiovascular diseases
Emergency medicine 324275 324275 0 0
Other emergency care

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Study treatment is open-label intravenous magnesium loading of 10mmol diluted in 100 mL normal saline infused over 1 hour if the serum magnesium level <1.5mmol/L followed by continuous intravenous infusion of 3mmol/hr (10mmol Magsenium sulfate diluted in 100ml of normal saline) followed by an infusion to aim for an ionised Mg level of 0.9 to 1.3 mmol/L (total serum magnesium of 1.5 to 2 mmol/L).
If the baseline ionised Mg level is 0.9 to 1.3 mmol/L (total magnesium of 1.5 to 2 mmol/L), the continuous intravenous infusion will start without the loading dose.
The study treatment will be delivered until one of the following occurs:
1. Vasoactive therapy and mechanical ventilation have been stopped
2. Four days have passed since start of treatment
3. Discharge from ICU
4. Onset of severe oliguria (<0.5 ml/kg/hr for 12 hours) or significant new renal dysfunction (a 50% increase in baseline serum creatinine)
5. Death
Each study ICU will use the method of administration for magnesium therapy for six months.
At the end of these six months, the ICU will then swap to the other routine administration method for the next six months.
Study treatment will only be administered in situations where the treating clinician believes magnesium treatment is required to assist with the optimisation of magnesium levels. There will be no other recommended changes in management. Day-to-day management and assessment of electrolyte replacement will be up to the treating clinician.
A flowchart regarding the administration of Magnesium will be provided at the bedside to guide the intervention protocol. Pre-printed blood tests will be provided for the appropriate dosage adjustment. A subsequent audit of bedside charts to confirm adherence to the intervention protocol.
Intervention code [1] 324082 0
Treatment: Drugs
Comparator / control treatment
The traditional (standard approach) of magnesium replacement via intermittent fixed boluses of magnesium as per the discretion of the treating clinician aiming for a level of > 0.7 mmol/L.
Control group
Active

Outcomes
Primary outcome [1] 332078 0
Duration of new-onset atrial fibrillation (collected via study-specific data collection sheet by bedside nurse)
Timepoint [1] 332078 0
4 days post study enrollment or until ICU discharge
Secondary outcome [1] 412112 0
Incidence of Atrial fibrillation (collected via data-link of electronic medical records)
Timepoint [1] 412112 0
Until ICU discharge
Secondary outcome [2] 412113 0
Incidence of fast Atrial fibrillation (collected via data-link of electronic medical records)
Timepoint [2] 412113 0
Until ICU discharge
Secondary outcome [3] 412114 0
Days alive and free of Atrial fibrillation analysed as a composite outcome collected via data-link to medical records.
Timepoint [3] 412114 0
Until ICU discharge
Secondary outcome [4] 412115 0
ICU-free days collected via data-linkage to medical records
Timepoint [4] 412115 0
At 28 days post ICU admission
Secondary outcome [5] 412116 0
Hospital-free days as collected via data-linkage to medical records
Timepoint [5] 412116 0
At 28 days post ICU admission
Secondary outcome [6] 412117 0
ICU Mortality as collected via data-linkage to medical records
Timepoint [6] 412117 0
At Hospital discharge
Secondary outcome [7] 412118 0
Hospital Mortality as collected via data-linkage to medical records
Timepoint [7] 412118 0
At hospital discharge
Secondary outcome [8] 412119 0
Duration of Mechanical ventilation as collected via data-linkage to medical records
Timepoint [8] 412119 0
During ICU admission
Secondary outcome [9] 412120 0
Duration of vasopressor and inotrope infusion will be assessed as a composite outcome and collected via data-linkage to medical records
Timepoint [9] 412120 0
During ICU admission
Secondary outcome [10] 412121 0
Clinical complications including delirium, stroke, pneumonia (as coded at ICU discharge using ICD-10 coding) as collected via data-linkage to medical records
Timepoint [10] 412121 0
At Hospital discharge
Secondary outcome [11] 412122 0
Use of other anti-arrhythmic agents (Amiodarone or Digoxin) as collected via data-linkage to medical records
Timepoint [11] 412122 0
During ICU admission

Eligibility
Key inclusion criteria
Patients who are invasively mechanically ventilated and receiving vasoactive agents.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients who are allergic to the allocated trial drug.
2. Patients who have undergone cardiac surgery.
3. Pre-eclampsia, eclampsia, or post-partum hypertension.
4. Patients who are known to have atrial fibrillation.
5. Patients with severe Chronic Kidney Disease (eGFR<30ml/min).
6. Patients who Have severe oliguria (<0.5 ml/kg/hr for 12 hours)
7. Patients with serum total Magnesium level of < 0.4mmol/l.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Multi-center cluster cross-over trial
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
These two methods of magnesium replacement have never been compared in any trials in mechanically ventilated adult ICU patients requiring vasoactive support. This is, therefore, a pilot study in order to determine the feasibility of comparing these two methods, as well as to establish the primary outcome of duration of new-onset atrial fibrillation at day 4 in non-cardiac surgery patient requiring vasoactive support. Furthermore, it will be used to establish baseline data within the secondary outcome.
As such, the method of administration will be used for defined periods of 6 months at each hospital, rather than aiming for a particular number of patients recruited. Provisional estimates of mechanically ventilated patients on vasopressors or inotropic support at each hospital would suggest that approximately 300 patients will be recruited. Thus, from previous ICU studies assuming that at least 20 patients will develop AF in each group, we would have a >90% power to detect a decrease in the typical duration of AF from 8 hours (as reported in the literature) to 5 hours with an SD of 2 hours.
Analysis will be conducted on an intention-to-treat basis. Analyses of the primary composite endpoint will involve cluster (ICU) summary measures obtained by aggregating the composite endpoint to a rate per ICU per time period and calculating the difference in event rates between the first and second periods for each ICU. these differences will then be entered as the dependent variable into an unweighted linear regression with randomised sequence as the independent variable, from which the coefficient of the randomised sequence is then the estimated two methods of magnesium replacement difference. Uncertainty concerning treatment effects will be estimated using standard 95% confidence intervals. For secondary outcomes on a binary scale the same methods will apply, and for outcomes on a continuous scale the linear mixed model methods will be applied.
Sensitivity analyses will be performed for the impact of patients with missing outcome data using multiple imputation methods. Categorical variables will be compared using the Pearson chi-square or Fisher exact test. Continuous variables will be assessed for normality. Normally distributed variables will be compared using student t-test, and nonparametric data will be compared utilising Wilcoxon rank-sum test.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
16/02/2023
Actual
16/02/2023
Date of last participant enrolment
Anticipated
1/03/2024
Actual
Date of last data collection
Anticipated
1/07/2024
Actual
Sample size
Target
300
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 22856 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 22857 0
Ballarat Health Services (Base Hospital) - Ballarat Central
Recruitment postcode(s) [1] 38161 0
3084 - Heidelberg
Recruitment postcode(s) [2] 38162 0
3350 - Ballarat Central

Funding & Sponsors
Funding source category [1] 311896 0
Hospital
Name [1] 311896 0
Austin Health
Country [1] 311896 0
Australia
Funding source category [2] 311974 0
Hospital
Name [2] 311974 0
Ballarat Base Hospital
Country [2] 311974 0
Australia
Primary sponsor type
Individual
Name
Prof Rinaldo Bellomo
Address
Austin Health
145 Studley Rd,
Heidelberg VIC 3084
Country
Australia
Secondary sponsor category [1] 313376 0
Individual
Name [1] 313376 0
Dr Khaled El-Khawas
Address [1] 313376 0
Ballarat Base Hospital part of Grampian Health
Intensive care Unit
1 Drummond St N,
Ballarat Central VIC 3350
Country [1] 313376 0
Australia
Secondary sponsor category [2] 313377 0
Individual
Name [2] 313377 0
A/Prof Glenn Eastwood
Address [2] 313377 0
Austin Health
145 Studley Rd,
Heidleberg VIC 3084
Country [2] 313377 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311331 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 311331 0
Ethics committee country [1] 311331 0
Australia
Date submitted for ethics approval [1] 311331 0
20/08/2021
Approval date [1] 311331 0
11/11/2021
Ethics approval number [1] 311331 0
HREC/77347/Austin-2021

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120742 0
Dr Khaled El-Khawas
Address 120742 0
Ballarat Base Hospital, Grampian Health
1 Drummond St N,
Ballarat Central VIC 3350
Country 120742 0
Australia
Phone 120742 0
+61 3 5320 6706
Fax 120742 0
Email 120742 0
[email protected]
Contact person for public queries
Name 120743 0
Glenn Eastwood
Address 120743 0
Austin Health
145 Studley Rd,
Heidelberg VIC 3084
Country 120743 0
Australia
Phone 120743 0
+61 3 9496 4835
Fax 120743 0
+61 3 9496 3932
Email 120743 0
[email protected]
Contact person for scientific queries
Name 120744 0
Rinaldo Bellomo
Address 120744 0
Austin Health
145 Studley Rd,
Heidelberg VIC 3084
Country 120744 0
Australia
Phone 120744 0
+61 3 9496 5000
Fax 120744 0
Email 120744 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
16703Ethical approval    384421-(Uploaded-21-07-2022-12-21-21)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.