Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12618001489280
Ethics application status
Approved
Date submitted
29/08/2018
Date registered
5/09/2018
Date last updated
15/03/2021
Date data sharing statement initially provided
7/08/2019
Date results information initially provided
15/03/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
An observational study of heparin administration and reversal during catheter ablation for atrial fibrillation (CA-AF).
Scientific title
A Heuristic Approach to determine the optimal method of Heparin Dosing and Reversal in all Patients Undergoing Anaesthesia for Catheter Ablation for Atrial Fibrillation (CA-AF)'
Secondary ID [1] 295955 0
None
Universal Trial Number (UTN)
U1111-1219-6648
Trial acronym
Heparin Heuristics
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prevention of micro embolism during Catheter Ablation for atrial fibrillation 309465 0
Condition category
Condition code
Cardiovascular 308300 308300 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Each patient serves as their own control for the purpose of observing intravenous protamine dosage.
The patients are grouped according to the type of point of care ACT measuring device, and the oral anticoagulant they are taking. Each patient will be compared only to the median value of the slope of the heparin dose-response curve, as indicated below.
The data has been collected during the Course of routine anaesthesia for patients, starting in 2009. Pre heparin ACT was added to the data collected in 2011.

Heparin and protamine are administered intravenously as part of standard procedure. Heparin is required because the cardiologist inserts catheters into the right and left atria, and there is a significant risk of embolism and stroke in the presence of atrial fibrillation during the procedure.

Each patient undergoing CA-AF is given an intravenous dose of heparin to achieve an ACT of between 300 and 400 seconds. As each patient responds to heparin in a different manner, each patient requires the dose to be individualised. Thereafter, a heparin infusion is started between 0.2 and 0.3 times the initial heparin dose per hour, and adjusted by administration or a bolus dose of heparin or altering the infusion rate to maintain the desired ACT. Between three and four hours after the start of the procedure, when the procedure is completed, a dose of protamine is administered intravenously to reverse the heparin and achieve an ACT similar to the ACT before the initial dose of heparin.

For purposes of the study, the patient is observed for the duration of anaesthesia. Information recorded for the study forms part of the normal anaesthetic record and would be recorded even if the study were not to take place. The approximate dose of protamine for reversal of heparin is 1 mG for every 1 mG (100 International Units) of heparin given to achieve the desired ACT.

The initial dose of heparin and the resultant ACT enables the slope the heparin dose (mg/Kg) or heparin concentration (units/mL) to be calculated. It is hoped that by calculating the median values over a large number of observations, that a mathematical model can be derived that would allow the median slope to be used to calculate a predictable dose of heparin for each individual patient to achieve the desired ACT. Once the individual heparin dose-response curve has been developed, subsequent doses of heparin can be calculated to maintain the ACT. Additionally, the pre-protamine ACT can be used in conjunction with the slope to calculate the approximate amount of active heparin, and hence the appropriate dose of protamine to reverse that heparin.
Intervention code [1] 312280 0
Not applicable
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 307270 0
Proportion of participants having an initial post-heparin activated clotting time in the desired range of between 300 and 400 seconds, using a point of care ACT measuring device such as the i-Stat. (http://www.pocttesting.org/uploads/1/8/3/5/18355427/_istat_act1.pdf).
The initial pre-heparin blood sample is taken from the arterial line, and subsequent samples taken during the procedure are taken from an intravenous catheter inserted as part of the procedure by the cardiologist.
Timepoint [1] 307270 0
The ACT is measured before heparin is given and ten minutes after the administration of heparin, and thereafter at 30 minute intervals.

The statistical analysis of the data will be carried out once all patients are admitted to the study.
Primary outcome [2] 307271 0
Proportion of participants having post-protamine ACT not statistically different from pre-heparin ACT.
The ACT is measured using using a point of care ACT measuring device such as the i-Stat three minutes after the intravenous administration of protamine. The pre-heparin ACT and post-protamine ACT are compared.

The statistical analysis of the data will be carried out once all patients are admitted to the study.
Timepoint [2] 307271 0
The ACT is measured immediately before heparin administration, after induction of anaesthesia. The Act is measured again, three minutes after after the reverse of heparin by intravenous administration of protamine.
Secondary outcome [1] 351355 0
The effect on the heparin dose-response curve due to the presence of different oral anticoagulants will be assessed by calculating the median value for each group and generating box and whisker plots.
Timepoint [1] 351355 0
The median and Winsorized mean slopes of the heparin dose-response curve are recalculated three minutes after each patient has been given the initial dose of heparin and the post-heparin ACT has been recorded.

Eligibility
Key inclusion criteria
All patients presenting for catheter ablation for atrial fibrillation, or implantation of a left atrial occlusion device.
Minimum age
20 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Known allergic response to heparin. In this case, heparin will not be used.
Known history of heparin induced thrombosis/thrombocytopenia

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Both
Statistical methods / analysis
Robust inferential methods are available that perform well with relatively small sample sizes, even in situations where classic methods based on means and variances perform poorly with relatively large sample sizes and have the potential of substantially increasing power even under slight departures from normality.{Mair P., Wilcox R, Robust Statistical Methods in R Using the WRS2 Package. Journal of Statistical Software. https://dornsife.usc.edu/assets/sites/239/docs/WRS2.pdf)

A paired samples t-test (Trimciv2) will be used to show the effect of protamine on the on the pre-protamine ACT. To test the relationship between pre-heparin ACT and post-protamine ACT, marginal trimmed means will be compared to test the hypothesis that the trimmed means of the marginal distributions are equal. The functions yuend and ydbt ( bootstrap method) will be used for this purpose.

Ref: Wilcox, Rand R.. Understanding and Applying Basic Statistical Methods Using R (Statistics in Practice) (p. 358). Wiley. Kindle Edition.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
9/03/2009
Date of last participant enrolment
Anticipated
12/08/2019
Actual
30/07/2020
Date of last data collection
Anticipated
12/08/2019
Actual
30/07/2020
Sample size
Target
600
Accrual to date
Final
710
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 11752 0
Greenslopes Private Hospital - Greenslopes
Recruitment postcode(s) [1] 23838 0
4120 - Greenslopes

Funding & Sponsors
Funding source category [1] 300494 0
Hospital
Name [1] 300494 0
Greenslopes Private Hospital - Greenslopes
Country [1] 300494 0
Australia
Primary sponsor type
Individual
Name
Philip Cumpston
Address
Cardiac Catheter Laboratory,
Greenslopes Private Hospital,
Newdegate Street
Greenslopes. QLD 4120
Country
Australia
Secondary sponsor category [1] 300043 0
None
Name [1] 300043 0
Address [1] 300043 0
Country [1] 300043 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301292 0
Greenslopes Research and Ethics Committee
Ethics committee address [1] 301292 0
Newdegate Street
Greenslopes. QLD 4120
Ethics committee country [1] 301292 0
Australia
Date submitted for ethics approval [1] 301292 0
01/08/2018
Approval date [1] 301292 0
14/08/2018
Ethics approval number [1] 301292 0
18/38

Summary
Brief summary
:This study was initiated to clarify the confusing response to heparin and the difficulty in obtaining adequate heparinisation during catheter ablation for atrial fibrillation (CA-AF). The initial pilot study enabled a more rational approach to heparin management, and after recruiting 500 patients into the study, analysis is progressing with a view to demonstrating a method that enables:
o accurate prediction of the heparin dose required to achieve an ACT with the desired range
o maintenance of the ACT within the desired range during the procedure
o a simple method for reversing the active heparin with protamine.
Trial website
Trial related presentations / publications
Public notes
Prior to data collection for review (March 2009), guidance was sought by the previous chair of the Greenslopes Research and Ethics Committee (GREC) as to the requirement to submit for review of the committee. It was advised that this was not required, as no data was being collected beyond that which is collected for standard care.
A formal review of this decision was carried out by the GREC in July 2018. At this meeting, formal approval was granted on the basis that the committee considered this to be a retrospective analysis of patient records keep by the principal investigator.

Contacts
Principal investigator
Name 86518 0
Dr Philip Cumpston
Address 86518 0
Cardiac Catheter Laboratory,
Greenslopes Private Hospital
Newdegate Street
Greenslopes. QLD 4120

All written :correspondence to
Dr Philip Cumpston
P.O. Box 742
Cooroy. QLD 4563
Country 86518 0
Australia
Phone 86518 0
+61730099914
Fax 86518 0
+61730099914
Email 86518 0
[email protected]
Contact person for public queries
Name 86519 0
Dr Philip Cumpston
Address 86519 0
Cardiac Catheter Laboratory
Greenslopes Private Hospital
Newdegate Street
Greenslopes. QLD 4120
Country 86519 0
Australia
Phone 86519 0
+61730099914
Fax 86519 0
+61730099914
Email 86519 0
[email protected]
Contact person for scientific queries
Name 86520 0
Dr Philip Cumpston
Address 86520 0
Cardiac Catheter Laboratory
Greenslopes Private Hospital
Newdegate Street
Greenslopes. QLD 4120
Country 86520 0
Australia
Phone 86520 0
+61730099914
Fax 86520 0
+61730099914
Email 86520 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Unidentified data from the study, including age, height,weight,sex,oral anticoagulant, estimated blood volume, pre-heparin ACT, heparin dose, post-heparin ACT, pre-protamine ACT, post-protamine ACT
When will data be available (start and end dates)?
beginning of September 2019 until end August 2020
Available to whom?
Australian and New Zealand anaesthetists carrying out research in this area
Available for what types of analyses?
comparative studies and after review by principle investigator
How or where can data be obtained?
Contact [email protected]


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Basic resultsNo 375865-(Uploaded-12-03-2021-13-32-47)-Basic results summary.docx
Plain language summaryNo Retrospective analysis of data collected during ca... [More Details]

Documents added automatically
No additional documents have been identified.