Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000757819p
Ethics application status
Not yet submitted
Date submitted
1/04/2021
Date registered
16/06/2021
Date last updated
16/06/2021
Date data sharing statement initially provided
16/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Validation of a method for heparin reversal with protamine in patients undergoing cardiac surgery.
Scientific title
Determination of the validity of a proposed method for estimating the appropriate dose of protamine for effective heparin reversal in patients undergoing cardiac surgery.
Secondary ID [1] 295904 0
None
Secondary ID [2] 304176 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiac Surgery 321865 0
Condition category
Condition code
Cardiovascular 319194 319194 0 0
Other cardiovascular diseases
Surgery 319195 319195 0 0
Other surgery

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
While guidelines for protamine administration have been published by several cardiac surgical societies, a number of different approaches are currently used. These include: 1. Giving protamine in a fixed 1:1 ratio (1mg. protamine to 1 mg or 100 International Units of heparin) based on the initial dose of heparin. 2. A fixed ratio of 1:1 based on the total dose of heparin administered during the case. 3. A ratio based on either the total dose of heparin given throughout the case or the initial heparin dose, depending on the individual anaesthetist/institution( waring from 0.5:1 to 1:1).

Doses of protamine derived from a heparin:activated clotting time (ACT) dose-response curve and estimated blood volume will be estimated for each patient, allowing the effective heparin concentration to be estimated at each ACT measured. This approach is aligned with clinical practice, as the estimated dose of protamine will be within the range normally used.

The post-protamine ACT is used to assess that an appropriate dose of protamine has been used, and this will be confirmed by viscoelastic testing. The pre-protamine ACT will be used to estimate the appropriate dose of protamine for heparin reversal after rewarming and before re-infusion of pump blood. Viscoelastic testing with the Clotpro or TEG6s will allow comparison of the clot times with and without heparinase to determine effectiveness of this predicted protamine dose in reversing heparin effect. Inadequate reversal will be treated with additional protamine in the usual manner by anaesthetic and surgical team.

The ACT is measured routinely throughout the cardiac surgical procedure. The creation of the heparin:ACT dose-response curve will require no additional blood samples over and above those that are normally used to confirm that an appropriate level of coagulation has been reached, apart from one blood sample taken prior to heparinisation. The volume of blood required is less than 5 mL.

The cardiac surgical procedures are those that require bypass, with anticoagulation achieved by using heparin. The duration varies depending on surgical difficulty but is usually longer than two hours. There will be no additional time require for performance of blood tests. If the dose of protamine estimated is the correct dose, total time will be reduced.

The minimum and maximum dose of heparin to be administered depends on the anaesthetist carrying out the procedure, and is not relevant to the calculation of protamine for the purpose of this study, as the dose of protamine is estimated by individual patient's response to the heparin as shown by the current ACT. The minimum dose of heparin to be administered will be in the order of 10,000 units, the maximum dose may be as high as to 80,000 units.

Heparinase is not administered to the patient, it ia component of the viscoelastic tests to compare the clotting time in a single sample of blood with and without the presence of heparin.
Heparin is given after the first incision and prior to going on to bypass.

Protamine is administered after rewarming, before re-infusion of pump blood. An ACT will be measured five minutes after the protamine is given. Viscoelastic testing is performed at this time to confirm that the heparin has bene reversed, and to determine if there are other factors that might contribute to ongoing bleeding.

Heparin and protamine are given by slow intravenous injection. Infusions are not used.

The purpose of this study is to determine how well the approach taken determines the appropriate dose of protamine to reverse active heparin based on the ACT before protamine is administered. The drugs used are those normally used in performing this surgery. Observation of the patient throughout the perioperative patient are the responsibility of the anaesthetic and surgical team performing the procedure, and is not a requirement of this study.
Intervention code [1] 320170 0
Not applicable
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 327063 0
Viscoelastic testing includes the measurement of clotting time on a sample of blood. The sample is tested without heparinase being added by the device, and with heparinase. The process is automated. Using a single sample of blood, a number of parameters are displayed.
The single end-point (primary outcome) is a calculation based on the clotting time without heparinase divided by the clotting time with heparinase. If it is close to 1, then the heparin in the sample has been reversed by the protamine given
The viscoelastic tests that will be used are the In-Test and HI-Test for the Rotem and the R time for the TEG 6s. If the IN-Test clotting time is more than 200 seconds and the IN-Test/HI-test rain is more than 1.25 a residual heparin effect is considered to be present. If the TEG 6s is used, the R time will be measured. If the CK/CK ratio is greater than 1.25 this will be considered as residual heparin effect.
Timepoint [1] 327063 0
The viscoelastic testing will be performed five minutes after the administration of protamine, at completion of surgery and rewarming of the patient prior to re-infusion of pump blood.
Secondary outcome [1] 395161 0
The activated clotting time measured five minutes after the administration of protamine.
Timepoint [1] 395161 0
Five minutes after the administration of protamine. This is given at completion of surgery and rewarming but before re-infusion of pump blood.

Eligibility
Key inclusion criteria
All adult patients undergoing cardiac surgery requiring the use of bypass and heparinisation.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Known adverse reaction to heparin and/or protamine

Study design
Purpose
Duration
Selection
Timing
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
9/08/2021
Actual
Date of last participant enrolment
Anticipated
1/01/2022
Actual
Date of last data collection
Anticipated
1/01/2022
Actual
Sample size
Target
90
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 19051 0
Greenslopes Private Hospital - Greenslopes
Recruitment hospital [2] 19052 0
Sunshine Coast University Private Hospital - Birtinya
Recruitment postcode(s) [1] 33599 0
4120 - Greenslopes
Recruitment postcode(s) [2] 33600 0
4575 - Birtinya

Funding & Sponsors
Funding source category [1] 300495 0
Self funded/Unfunded
Name [1] 300495 0
Country [1] 300495 0
Primary sponsor type
Individual
Name
Dr Philip Cumpston
Address
Dr Philip Cumpston Private Practice
Contact mail at the following address:
P.O. Box 742 Cooroy QLD 4563
Country
Australia
Secondary sponsor category [1] 299972 0
None
Name [1] 299972 0
Address [1] 299972 0
Country [1] 299972 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 301293 0
Ramsay Health Care QLD Human Research Ethics Committee
Ethics committee address [1] 301293 0
Ethics committee country [1] 301293 0
Australia
Date submitted for ethics approval [1] 301293 0
02/08/2021
Approval date [1] 301293 0
Ethics approval number [1] 301293 0

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

Contacts
Principal investigator
Name 86522 0
Dr Philip Cumpston
Address 86522 0
Dr Philip Cumpston Private Practice
P.O. Box 742 Cooroy QLD 4563
Country 86522 0
Australia
Phone 86522 0
+61 411020343
Fax 86522 0
+61 7 30099914
Email 86522 0
pcumpston@icloud.com
Contact person for public queries
Name 86523 0
Philip Cumpston
Address 86523 0
Dr Philip Cumpston Private Practice
P.O. Box 742 Cooroy QLD 4563
Country 86523 0
Australia
Phone 86523 0
+61 411020343
Fax 86523 0
+61 7 30099914
Email 86523 0
pcumpston@icloud.com
Contact person for scientific queries
Name 86524 0
Philip Cumpston
Address 86524 0
Dr Philip Cumpston Private Practice
P.O. Box 742 Cooroy QLD 4563
Country 86524 0
Australia
Phone 86524 0
+61 411020343
Fax 86524 0
+61 7 30099914
Email 86524 0
pcumpston@icloud.com

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 analysed to produce the conclusions reached.
This will include:
ACT prior to heparinisation
ACT prior to reversal of heparin with protamine
ACT taken five minutes after protamine is given
The viscoelastic test indicating clot times with and without heparinase
When will data be available (start and end dates)?
for one year after completion of analysis and publication of results.
Available to whom?
accredited researchers
Available for what types of analyses?
any purpose
How or where can data be obtained?
Access subject to approvals by Principal Investigator:
pcumpston@icloud.com


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.