Apixaban for the Acute Treatment of Venous Thromboembolism in Children

Study Overview
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Brief Summary
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To assess the safety and descriptive efficacy of apixaban in pediatric subjects requiring anticoagulation for the treatment of a VTE.

Official Title
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A RANDOMIZED, OPEN-LABEL, ACTIVE CONTROLLED, SAFETY AND DESCRIPTIVE EFFICACY STUDY IN PEDIATRIC SUBJECTS REQUIRING ANTICOAGULATION FOR THE TREATMENT OF A VENOUS THROMBOEMBOLIC EVENT

Conditions
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Venous Thromboembolism

Intervention / Treatment
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* Drug: Apixaban
* Drug: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Birth to <18 years of age with a minimum weight of 2.6 kg at the time of randomization. Presence of an index VTE which is confirmed by imaging. Intention to manage the index VTE with anticoagulation treatment for at least 6 to 12 weeks. Subjects able to tolerate oral feeding, nasogastric (NG), gastric (G) feeding and are currently tolerating enteric medications, as per investigator's judgement. Exclusion Criteria: Anticoagulant treatment for the index VTE for greater than 14 days prior to randomization. Neonates that are enrolled into the PK cohort must be on a minimum of 5 days and a maximum of 14 days SOC anticoagulation prior to randomization. Neonates that are enrolled into the post PK cohort may receive SOC anticoagulation for up to 14 days prior to randomization. Thrombectomy, thrombolytic therapy, or insertion of a caval filter to treat the index VTE. A mechanical heart valve. Active bleeding or high risk of bleeding at the time of randomization. Intracranial bleed, including intraventricular hemorrhage, within 3 months prior to randomization. Abnormal baseline liver function at randomization. Inadequate renal function at the time of randomization. Platelet count <50×109 per L at randomization. Uncontrolled severe hypertension at the time of randomization. Use of prohibited concomitant medication at the time of randomization. Female subjects who are either pregnant or breastfeeding a child. Use of aggressive life-saving therapies such as ventricular assist devices (VAD) or extracorporeal membrane oxygenation (ECMO) at the time of enrollment. Unable to take oral or enteric medication via the NG or G tube. Known inherited or acquired antiphospholipid syndrome (APS). Known inherited bleeding disorder or coagulopathy with increased bleeding risk (eg, hemophilia, von Willebrand disease, etc.)

Ages Eligible for Study
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Minimum Age: 0 Days
Maximum Age: 17 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apixaban<br>Subjects between birth to <18 years will be dosed on a body weight tiered regimen. Subjects ≥35kg will receive 10mg twice daily(BID) for 7 days followed by 5mg BID thereafter;<35kg to 25kg will receive 8mg BID for 7 days followed by 4mg BID thereafter;<25 to 18kg will receive 6mg BID for 7 days and then 3mg BID thereafter;<18 to 12kg will receive 4mg BID for 7 days and then 2mg BID thereafter;<12 to 9kg will receive 3mg BID for 7 days and then 1.5mg BID thereafter;< 9kg to 6kg will receive 2 mg BID for 7 days and 1mg BID thereafter;<6kg to 5kg will receive 1mg BID for 7 days and 0.5mg BID thereafter;<5kg to 4kg will receive 0.6mg twice daily for 7 days and 0.3mg BID thereafter;PK cohort neonates ≥ 2.6kg will receive 0.1mg BID. Dose will be adjusted as determined by PK measurements (ie, to 0.2mg BID, 0.1mg daily or dose will stay the same).For the post PK cohort Neonates ˂4kg to 2.6kg, if confirmed by PK sub analysis,subjects will receive 0.2mg BID for 7 days and 0.1mg BID thereafter. | Drug: Apixaban<br>* Tablet or Solution<br>Drug: Standard of Care<br>* Unfractionated heparin, low molecular weight heparin, and/or a vitamin K antagonist. For subjects under 2 years of age, standard of care will be limited to unfractionated heparin or low molecular weight heparin.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The composite of major and clinically relevant non major bleeding. | The composite of major and clinically relevant non major bleeding. | up to 12 weeks | 
| A composite of all image confirmed and adjudicated symptomatic and asymptomatic recurrent VTE and VTE related mortality. | A composite of all image confirmed and adjudicated symptomatic and asymptomatic recurrent VTE and VTE related mortality. | up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apixaban concentration | Apixaban concentration | Day 14 | 
| Anti-Xa Levels | Anti-Xa Levels | Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VTE, thromboembolism, thrombosis, embolism, apixaban, Eliquis