Efficacy of Apixaban in Malignancy With Deep Venous Thrombosis

Study Overview
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Brief Summary
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The aim of study was to evaluate the efficacy and safety of Apixaban in patients with acute deep venous thrombosis and active malignancy compared with weight adjusted subcutaneous (LMWH). It was hypothesised that Apixaban could be as effective as rivaroxiban and edoxaban in treatment of patients with acute DVT and active malignancy with a lower risk of bleeding especially in those with GIT cancer.

Detailed Description
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Patients with active malignancy have hypercoagulable state particularly, those receiving intravenous chemotherapy, with six fold higher risk of venous thromboembolism (VTE) [1]. Anticoagulation for malignancy associated deep venous thrombosis (DVT) can be difficult because of different limitations like bleeding, drug-drug interactions with chemotherapy and inconvenience with repeated subcutaneous injections of low-molecular-weight heparin (LMWH) [2]. In comparison with patients without active malignancy, patients with cancer who are on warfarin therapy have 2 to 6 folds more major bleeding events and 2 to 3 times more VTE recurrence [3,4]. The American College of Chest Physicians Guidelines recommended (LMWH) as standard therapy for management of acute VTE in patients with active malignancy [5]. Recently, Rivaroxiban and Edoxaban were considered as an alternative to weight-adjusted subcutaneous LMWH after pulmonary embolism in patients with active cancer without gastrointestinal (GIT) malignancy [6]. Apixaban is a direct factor Xa inhibitor approved by FDA for treatment of DVT and VTE [7]. However its efficacy in management of acute DVT and VTE associated with cancer is still unresolved issue. The aim of study was to evaluate the efficacy and safety of Apixaban in patients with acute deep venous thrombosis and active malignancy compared with weight adjusted subcutaneous (LMWH).

Official Title
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Efficacy and Safety of Apixaban in Patients With Active Malignancy and Acute Deep Venous Thrombosis.

Conditions
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Deep Vein Thrombosis, Malignancy

Intervention / Treatment
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* Drug: Apixaban
* Drug: Enoxaparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients with active malignancy presenting with acute deep venous thrombosis and still treated with chemotherapy Exclusion Criteria: Patients with pulmonary embolism and hemodynamic instability requiring thrombolytic therapy Previous DVT or venous thromboembolism Administration of LMWH or unfractionated heparin before randomization Brain tumours, cerebral metastes, hepatic tumours or impairment Child-Pugh B or C, -Recent or current active or life threating bleeding (e.g. intr acranial haemorrhage or gastrointestinal bleeding) Thrombocytopenia (platelets <100 x 109L) Severe chronic kidney disease (estimated glomerular filtration rate <30 ml/minute) Pregnant women

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Apixaban<br>50 patients with DVT with malignancy were randomized to apixaban 10 mg twice daily dose for 7 days followed by apixaban 5 mg twice daily | Drug: Apixaban<br>* 10 mg/12 h for 1 week followed by 5 mg/12 h<br>|
| Active Comparator: Enoxaparin<br>50 patients with DVT with malignancy were randomized to enoxaparin (1mg/Kg/SC every 12 h) | Drug: Enoxaparin<br>* 1mg/Kg/sc/12h<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrent deep venous thrombosis or venous thromboembolism | New or non resolving completely occluded deep venous thrombosis or occurrence of pulmonary embolism | 6 months | 
| Occurrence of fatal or major bleeding | Need for hospitalization, blood transfusion, surgical intervention or resulting into death | 6 months | 
| Mortality related to massive pulmonary embolism | Death caused by hemodynamic instability secondary to massive pulmonary embolism | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of non-fatal or minor bleeding | Bleeding that does not need hospitalization, blood transfusion, surgical intervention or resulting into death | 6 months |