Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000642684
Ethics application status
Approved
Date submitted
10/06/2014
Date registered
18/06/2014
Date last updated
26/07/2019
Date data sharing statement initially provided
26/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Characterization of endothelial function, arterial stiffness and inflammation in Atrial Fibrillation: Effect of cardioversion
Scientific title
Characterization of endothelial function, arterial stiffness and inflammation in Atrial Fibrillation: Effect of cardioversion
Secondary ID [1] 284764 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial fibrillation
 292135 0
Condition category
Condition code
Cardiovascular 292469 292469 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Electrical cardioversion

Cardioversion will be performed on patients who were fasted for up to eight hours prior to the procedure. Patients will be sedated with midazolam and a 150J biphasic shock will be used to reset SR. Patients will be closely monitored by trained staff for the duration of the procedure and discharged when clinically stable and fully recovered from sedation (within 1.5 hours post cardioversion for all patients).
Intervention code [1] 289559 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 292332 0
The objective of our studies is to evaluate the effects of reverting AF patients (n=60) back to sinus rhythm via cardioversion and the effect this has on endothelial function.

The EndoPAT device was utilised to non-invasively measure endothelial function. One PAT finger probe is placed on the index finger of the hand undergoing hyperemia testing (right hand), and a second PAT probe was placed on the contralateral index finger (left hand) and is used as a control. Patients will be recumbent and rested prior to endothelial function evaluation.

Endothelial dependent response relates to flow mediated increase in pulse wave amplitude (PWA) following 5 minute pneumatic cuff occlusion of the brachial artery. The PAT hyperemia ratio is defined as the ratio of the average PWA during the 1-minute period beginning exactly 60 seconds of reactive hyperemia compared with the average PWA during a 210-second preocclusion baseline period. In an effort to decrease confounding variables, including potential systemic effects of unilateral arm ischaemia, this ratio is normalized to the concurrent signal from the contralateral, nonischemic hand. PAT measurements will be analyzed with a computerized, automated algorithm (Itamar Medical Ltd, Caesarea, Israel).
Endothelial function was also measured with Eliza assays of Asymmetric dimethyl arginine (ADMA) and flow cytometry assessing von Willebrand factor (vWF).
Timepoint [1] 292332 0
Prior to cardioversion procedure
Within 6 hours post-procedure
7 days after procedure
3 months post-procedure
Primary outcome [2] 292335 0
The objective of our studies is to evaluate the effects of reverting AF patients (n=60) back to sinus rhythm via cardioversion and the effect this has on inflammation.

Inflammation will be assessed using ELIZA assays of Soluble CD40L, routine biochemical assays of hs-CRP and flow-cytometry of CD40-CD40L.
Timepoint [2] 292335 0
Prior to cardioversion procedure
Within 6 hours post-procedure
7 days after procedure
3 months post-procedure
Primary outcome [3] 292383 0
The objective of our studies is to evaluate the effects of reverting AF patients (n=60) back to sinus rhythm via cardioversion and the effect this has on arterial stiffness.

Aortic pulse wave velocity (PWV) and augmentation index (AIx) are commonly used noninvasive measurements of arterial stiffness and wave reflection strength, respectively. We have recently purchased, a new device (SphygmoCor Xcel; AtCor Medical) which measures AIx using a partially inflated brachial cuff and PWV using a partially inflated femoral cuff together with carotid applanation tonometry.
To assess AIx, brachial artery compression waveforms will be obtained by partially inflating a cuff over the brachial artery approximately midway between the shoulder and the elbow. The brachial waveforms are calibrated using cuff-measured brachial systolic and diastolic pressures, and then used to generate central aortic pressure waveforms by applying proprietary digital signal processing and transfer function. The central aortic pulse wave is used to determine AIx: the ratio of wave reflection amplitude to central pulse pressure. To assess PWV, carotid pulse waves are measured by applanation tonometry (high-fidelity micromanometer; Millar instruments) and femoral pulse waves are simultaneously obtained by a partially inflated cuff over the femoral artery at the leg midway between the hip and the knee. PWV is determined by calculating the ratio of the corrected distance between the pulse measuring sites to the time delay between the carotid and femoral pulse waves. The distance is measured with a nonstretchable tape (1) from the suprasternal notch to the carotid site, (2) from the femoral artery at the inguinal ligament to the proximal edge of the thigh cuff and (3) from the suprasternal notch to the proximal edge of the thigh cuff. Distances 1 and 2 were subtracted from distance 3 and used in the calculation of PWV.
Timepoint [3] 292383 0
Prior to cardioversion procedure
Within 6 hours post-procedure
7 days after procedure
3 months post-procedure
Secondary outcome [1] 308727 0
nil
Timepoint [1] 308727 0
nil

Eligibility
Key inclusion criteria
This study will consist of evaluating patients who are undergoing a therapy directed at restoring sinus rhythm, ie. electrical cardioversion; patients of both sexes aged > 18 yrs meeting the following criteria will be enrolled. Consecutive patients with AF undergoing elective cardioversion at the Royal Adelaide Hospital or Wakefield Hospital will be eligible for this study. Endothelial function testing will be performed pre and 2 hours post procedure.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will be excluded if they have known causes of acute AF (such as pneumonia or other infections, alcohol excess, pulmonary embolism), significant heart valve disease, acute cardiovascular or cerebrovascular events (myocardial infarction, acute coronary syndrome or stroke) within the last 3 months, malignancy, connective tissue disease, chronic infection, inflammatory conditions, renal or hepatic dysfunction. We will exclude patients who, for any reason, are contra-indicated to undergo cardioversion of AF. As a final exclusion, patients unable to undergo a brief general anaesthetic will not be enrolled.

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)
Allocation not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
Continuous variables will be reported as mean +/- SD and evaluated utilizing an unpaired Student’s t-test or the Mann Whitney U tests (if non-Gaussian). Categorical variables will reported as numbers and percentage, and compared using the Fisher’s exact test. Sequential data measurements will be evaluated by 1-way ANOVA with repeated measures followed by the Bonferroni’s procedure for posthoc analysis. Statistical significance is established at p<0.05.

Sizing calculation: From previously generated preliminary data in patients with atrial fibrillation (n=16). Baseline endothelial function as measured by EndoPAT = 1.6 +/- 0.3 RHI. 2 hours after cardioversion endothelial function as measured by endopat = 1.8 +/- 0.4 RHI. Hence power calculation: to detect an increase in baseline RHI of 1.0xSD by cardioversion at 2 hours at P< 0.05, we approximate that 60 patients will be needed (a=0.8).

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Date of first participant enrolment
Anticipated
20/06/2014
Actual
Date of last participant enrolment
Anticipated
10/06/2015
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 2611 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 8287 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 289381 0
University
Name [1] 289381 0
Centre for Heart Rhythm Disorders University of Adelaide
Country [1] 289381 0
Australia
Primary sponsor type
University
Name
Centre for Heart Rhythm Disorders University of Adelaide
Address
Adelaide SA 5000 Australia
Country
Australia
Secondary sponsor category [1] 288068 0
None
Name [1] 288068 0
Address [1] 288068 0
Country [1] 288068 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291145 0
Research Ethics Committee Royal Adelaide Hospital
Ethics committee address [1] 291145 0
Level 3 Hanson Institute, IMVS Building, RAH
North Terrace, Adelaide SA 5000
Ethics committee country [1] 291145 0
Australia
Date submitted for ethics approval [1] 291145 0
29/05/2014
Approval date [1] 291145 0
10/06/2014
Ethics approval number [1] 291145 0
HREC/14/RAH/206

Summary
Brief summary
The purpose of this study is to investigate if restoring sinus rhythm in patients with atrial fibrillation by cardioversion is associated with impairment of endothelial function, arterial stiffness and inflammation.

The hypotheses to be tested include:
1) Restoration of sinus rhythm by cardioversion will adversely affect endothelial function, arterial stiffness and inflammation.
2) The length of time patients remain in sinus rhythm will correlate significantly with changes in endothelial function, arterial stiffness and inflammation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 49086 0
Dr Scott Willoughby
Address 49086 0
Centre for Heart Rhythm Disorders
University of Adelaide
Adelaide SA 5000 Australia
Country 49086 0
Australia
Phone 49086 0
+61 8 8313 0131
Fax 49086 0
+61 8 8222 2722
Email 49086 0
scott.willoughby@adelaide.edu.au
Contact person for public queries
Name 49087 0
Dr Scott Willoughby
Address 49087 0
Centre for Heart Rhythm Disorders
University of Adelaide
Adelaide SA 5000 Australia
Country 49087 0
Australia
Phone 49087 0
+61 8 8313 0131
Fax 49087 0
+61 8 8222 2722
Email 49087 0
scott.willoughby@adelaide.edu.au
Contact person for scientific queries
Name 49088 0
Dr Scott Willoughby
Address 49088 0
Centre for Heart Rhythm Disorders
University of Adelaide
Adelaide SA 5000 Australia
Country 49088 0
Australia
Phone 49088 0
+61 8 8313 0131
Fax 49088 0
+61 8 8222 2722
Email 49088 0
scott.willoughby@adelaide.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Trial was not undertaken


What supporting documents are/will be available?

No Supporting Document Provided



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.