Ticagrelor in Post-transplant Patients With Pediatric Hepatic Artery Thrombosis (HAT)

Study Overview
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Brief Summary
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Hepatic artery thrombosis (HAT) represents a major cause of graft loss and mortality after Pediatric liver transplantation. Ticagrelor (a new reversible inhibitor of P2Y12 receptor with faster onset of action and greater platelet inhibition) was used to treat patients with pediatric post-transplant hepatic artery thrombosis (HAT) compared to low molecular weight heparin.

Detailed Description
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In pediatric patients with post-transplant hepatic artery thrombosis (HAT) , low molecular weight heparin is a commonly used method. Ticagrelor, a direct-acting and reversible ADP receptor antagonist, is now the most commonly used ADP receptor antagonist in the treatment of coronary diseases. Compared to its predecessor clopidogrel, the pharmacokinetic profil of ticagrelor is more predictable, demonstrating a faster onset of action and a more consistent platelet inhibition. However, because of the excellent antithrombotic effect and increased bleeding potential, it is recommended that major bleeding, such as OPCAB or CABG surgery, be expected with a high probability, and in case of fatal surgery, the drug should be discontinued for 5 days. The present study is to evaluate the safety and efficacy of Ticagrelor in pediatirc receipt with post-operative HAT.

Official Title
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Determine the Safety/Efficacy of Ticagrelor in Post-transplant Patients With Hepatic Artery Thrombosis (HAT)

Conditions
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Hepatic Artery Thrombosis, Liver Transplant; Complications, Pediatric Disease

Intervention / Treatment
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* Drug: Ticagrelor Oral Tablet [Brilinta]
* Drug: Low molecular weight heparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age from 2 months to 5 years old. voluntary participation in clinical trials, and informed consent; Contrast- Enhanced Ultrasonography proved HAT Exclusion Criteria: History of sensitivity to study medications or any of their excipients Renal failure (eGFR <30 or requiring dialysis) A known bleeding diathesis, hemostatic or coagulation disorder, or prior major bleeding Prior stroke Active pathological bleeding History of intracranial haemorrhage Life expectancy <12 months based on investigator's judgement Patients considered to be at risk of bradycardic events (e.g., known sick sinus syndrome or second or third degree atrioventricular [AV)] block) unless already treated with a permanent pacemaker Anemia (hematocrit < 27%) Platelet count < 100,000/ml Concomitant use of strong CYP 3A inhibitors or inducers

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ticagrelor, 2-3mg/kg, 12h<br>2-3mg/kg, q12h, p.o. for 2w | Drug: Ticagrelor Oral Tablet [Brilinta]<br>* Ticagrelor, 2-3mg/kg, 12h, p.o.<br>* Other names: Ticagrelor;|
| Active Comparator: low molecular weight heparin<br>half amount low molecular weight heparin | Drug: Low molecular weight heparin<br>* half amount low molecular weight heparin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Contrast-Enhanced Ultrasonography-Based Hepatic Perfusion Index | The peak systolic maximum velocity (Vmax) of the HA, and HA resistive index (HARI) | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| High on-treatment platelet reactivity (HPR) | HPR defined as platelet reactivity index (PRI) ≥50% using VASP analysis | Two hours after the injection of either active drug or placebo | 
| Post-operative major bleeding event | post-operative major bleeding defined as HAT related bleeding | within 72 hours after operation |