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Trial registered on ANZCTR


Registration number
ACTRN12623001208695
Ethics application status
Approved
Date submitted
24/08/2023
Date registered
23/11/2023
Date last updated
23/11/2023
Date data sharing statement initially provided
23/11/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effectiveness of aspirin in children undergoing heart surgery
Scientific title
Platelet responsiveness to Aspirin as measured using Light Transmission Aggregometry (LTA) and Thromboelastography with platelet mapping (TEG-PM) in children after Heart Surgery.
Secondary ID [1] 310266 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Congenital heart disease 331243 0
Aspirin resistance 331244 0
Condition category
Condition code
Cardiovascular 328002 328002 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
Participants in this study will have blood samples drawn to evaluate the effectiveness of aspirin therapy in pediatric patients undergoing heart surgery and who need anti-platelet therapy after surgery.

Administration of aspirin is standard for care for the participants of this study. Prior to this study and in most places around the world, aspirin is administered without testing for its efficacy.

Aspirin is initiated as soon as enteral feeding is initiated.

Frequency of aspirin test:
1. Before administration of aspirin
2. After at least 3 days of aspirin therapy
3. After at least 3 days of increased aspirin dose (only if not responsive to routine dose)
Patients are followed up for 6 months post-surgery for evidence of clots
Intervention code [1] 326853 0
Early Detection / Screening
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 335866 0
Inadequate response to aspirin as determined by LTA demonstrating >/=20% platelet aggregation stimulated by arachidonic acid
Timepoint [1] 335866 0
After at least 3 days of adequate aspirin therapy - usually prior to hospital discharge, in rare circumstances at next outpatient visit
Secondary outcome [1] 425926 0
Inadequate response to aspirin as measure by TEG demonstrating >/=70% platelet aggregation stimulated by ADP< 50% inhibition of platelet function on TEG-PM on maximum permissible dose of aspirin
Timepoint [1] 425926 0
After at least 3 days of increased aspirin therapy - usually prior to hospital discharge, in rare circumstances at next outpatient visit
Secondary outcome [2] 425927 0
Measurement of dose-dependent response to aspirin in patients with an initial inadequate response to aspirin using LTA and TEG to an increased dose of aspirin
Timepoint [2] 425927 0
If LTA test demonstrates inadequate response to aspirin, the dose of aspirin is increased after consultation with a haematologist and is then retested after at least 3 days of the increased dose - usually prior to hospital discharge, in rare circumstances at next outpatient visit.
Secondary outcome [3] 425928 0
4) Incidence of thrombosis as defined by.
a. All cardiac thromboses visualised on cardiac imaging (echocardiogram, cardiac computed tomography, or magnetic resonance imaging).
b. All clinically significant non-cardiac thromboses causing symptoms and signs requiring medical review and ultrasound
c. Does not include thrombosis at site of vascular access.
Timepoint [3] 425928 0
12 weeks and 6 months after initiation of aspirin therapy
Secondary outcome [4] 425929 0
5) Incidence of clinically significant bleeding complications (ISTH guidance for definitions) as identified from electronic medical recorded
a. Major bleeding
i. Fatal bleeding and/or
ii. Symptomatic bleeding in a critical area or organ such as gastrointestinal, intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial or intramuscular with compartment syndrome
iii. Bleeding causing a fall in haemoglobin of 2g/dL or more leading to transfusion of >15ml/kg
b. Clinically relevant minor bleeding
i. A hospital admission for bleeding or
ii. A physician guided medical or surgical treatment for bleeding or
iii. A change in antithrombotic thvident/reported clinicallyerapy (including interruption or discontinuation of aspirin)
Timepoint [4] 425929 0
Up to 6 months after surgery

Eligibility
Key inclusion criteria
• Age 0-18 years of age
• Family/carer/patient able to provide informed consent.
• Children who require aspirin thromboprophylaxis after cardiac surgery such as;
• Systemic to pulmonary artery shunts
• Cavo-pulmonary shunt
• Fontan procedure
• Right ventricle to pulmonary artery conduit implantation
• Repairs involving large intra-cardiac baffles
• Valve repairs
• Any other patient receiving thromboprophylaxis with aspirin who does not meet the exclusion criteria
Minimum age
0 Days
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Patients with documented allergic reaction to aspirin
• Patients in whom aspirin is contra-indicated due to past adverse reactions such as Reye’s syndrome or renal dysfunction
• Patients on long-term anticoagulation with other drugs in addition to aspirin e.g. warfarin, clopidogrel or other antiplatelet medications.
• Relative contraindication: Patients who had GI bleeds associated with aspirin in the past should be assessed carefully, but not excluded immediately, given that aspirin can cause gastritis in any patient if they are fasted, have a concurrent illness etc

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
1 Sample Size Estimation
Sample sizes have been calculated based on the annual population of patients requiring thrombotic prophylaxis using aspirin seen at our institution which is approximately 200 cases per year. Using a 95% confidence interval and with a 5% margin of error we will need to recruit a total of 132 participants.

2 Statistical Analysis Plan
Data analysis will be conducted using the appropriate measures of spread and locations. Prior to analysis, a rigorous process of data cleaning to check outlying figures, missing, and implausible data against source data will be undertaken. Descriptive statistics will be used to summarise patient characteristics. Parametric or nonparametric techniques appropriate to the distribution of data will be applied. Results of the study will inform the future prophylactic management of thrombosis in children undergoing cardiac surgery in our institution.

3 Interim Analyses
Description of any interim analyses and stopping guidelines, including who will have access to these interim results and make the final decision to terminate the trial.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
17/10/2022
Date of last participant enrolment
Anticipated
31/12/2023
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
132
Accrual to date
93
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 25448 0
Queensland Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 41195 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 314473 0
Hospital
Name [1] 314473 0
Study Education and Research Trust Account (SERTA) funded by Children's Health Queensland (CHQ)
Country [1] 314473 0
Australia
Primary sponsor type
Hospital
Name
Children's Health Queensland Hospital and Health Service
Address
Queensland Children's Hospital501 Stanley Street,South BrisbaneQLD 4101
Country
Australia
Secondary sponsor category [1] 316629 0
None
Name [1] 316629 0
Address [1] 316629 0
Country [1] 316629 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313524 0
Children's Health Queensland Human Research Ethics Committe (CHQ HREC)
Ethics committee address [1] 313524 0
Queensland Children's Hospital501 Stanley Street,South Brisbane, QLD 4101
Ethics committee country [1] 313524 0
Australia
Date submitted for ethics approval [1] 313524 0
01/02/2022
Approval date [1] 313524 0
15/02/2022
Ethics approval number [1] 313524 0
HREC/22/QCHQ/79527

Summary
Brief summary
A significant number of neonates and infants require systemic-to-pulmonary artery shunt procedures as a part of staged treatment of their congenital cardiac condition. These shunts are at risk of thrombotic occlusion. Shunt patency is critical for survival of these children. The interim mortality of shunt dependent children has been found to be as high as 14%, and about 33% of these are due to thrombosis of the shunt. Some eventually undergo correction of their cardiac anomalies while the remaining undergo further surgeries for a single ventricle palliation (Fontan pathway). The children with single ventricle palliation are dependent on the patency of their subsequent shunts for survival. They are at risk of life-threatening thrombosis throughout their lives. Cross-sectional surveys of post-Fontan patients have reported a prevalence of intracardiac thrombosis of 17% to 33% and incidences of venous thrombosis and stroke ranging from 3% to 19%. The reported mortality from post-Fontan surgery thromboembolism is 25%. Aspirin has been the cornerstone of thromboprophylaxis in such children and its use has been associated with a significantly lower risk of mortality. Unfortunately, not all children respond equally to aspirin with an increase in the dose of aspirin suggested to reduce the incidence of thrombosis in some while the remaining have no response to aspirin. The prevalence of aspirin unresponsiveness in adults is estimated to be 0.4 to 35%, however this information in lacking in the paediatric population. The primary objective of the study is therefore to determine the prevalence of aspirin resistance in children undergoing cardiac surgery in Queensland. Secondary objectives are: 1) to assess if response to aspirin is dose dependent and 2) assess the incidence of thrombosis in children who respond to aspirin.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 128442 0
A/Prof Nelson Alphonso
Address 128442 0
Queensland Children's Hospital501 Stanley Street,South BrisbaneQLD 4101
Country 128442 0
Australia
Phone 128442 0
+61 7 30685775
Fax 128442 0
Email 128442 0
[email protected]
Contact person for public queries
Name 128443 0
Nelson Alphonso
Address 128443 0
Queensland Children's Hospital501 Stanley Street,South BrisbaneQLD 4101
Country 128443 0
Australia
Phone 128443 0
+61 7 30685775
Fax 128443 0
Email 128443 0
[email protected]
Contact person for scientific queries
Name 128444 0
Nelson Alphonso
Address 128444 0
Queensland Children's Hospital501 Stanley Street,South BrisbaneQLD 4101
Country 128444 0
Australia
Phone 128444 0
+61 7 30685775
Fax 128444 0
Email 128444 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
Patient privacy.
Cohort data will be available in the form of a publication.


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.