Cancer Venous Thromboembolism (VTE)

Study Overview
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Brief Summary
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The primary objective is to demonstrate the non-inferiority of edoxaban (preceded by a short course of LMWH) compared with dalteparin for the prevention of the combined outcome of recurrent venous thromboembolism (VTE) or major bleeding in subjects with VTE associated with cancer during a 12-month study period. If non-inferiority is established, LMWH/edoxaban will be compared with dalteparin for superiority.

Official Title
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A Phase 3b, Prospective, Randomized, Open-label, Blind Evaluator (PROBE) Study Evaluating the Efficacy and Safety of (LMW) Heparin/Edoxaban Versus Dalteparin in Venous Thromboembolism Associated With Cancer

Conditions
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Venous Thromboembolism (VTE), Deep Vein Thrombosis (DVT), Pulmonary Embolism (PE), Cancer

Intervention / Treatment
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* Drug: Edoxaban
* Drug: Dalteparin
* Drug: Low molecular weight heparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects with age ≥ 18 years or the otherwise legal lower age according to the country of residence; Confirmed acute lower extremity proximal DVT or PE for which long term treatment with low molecular weight heparin (LMWH) is indicated; Cancer, other than basal-cell or squamous-cell carcinoma of the skin; Able to provide written informed consent. Exclusion Criteria: Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current (index) episode of DVT and/or PE; Treatment with therapeutic doses of an anticoagulant other than that used for pretreatment of the current (index) VTE episode prior to randomization; Active bleeding or high risk for bleeding contraindicating treatment with LMWH or edoxaban; Any other contraindication listed in the local labeling of dalteparin, enoxaparin, or edoxaban;

Ages Eligible for Study
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Minimum Age: 18 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: Edoxaban group<br>After 5 days of low molecular weight heparin (LMWH), patients receive edoxaban treatment daily - tablet for oral use | Drug: Edoxaban<br>* After the 5 day treatment with LMWH, patients receive edoxaban 60 mg once daily (QD) as 2 × 30 mg tablets (or 1 x 30 mg tablet QD for patients requiring dose adjustment) for the remainder of the treatment period.<br>* Other names: DU-176b;Drug: Low molecular weight heparin<br>* Therapeutic doses of subcutaneous LMWH were administered for at least 5 days (to patients in the edoxaban group); this 5-day period may have included the pre-randomization LMWH (if applicable). The choice of parenteral LMWH was up to the treating physician.<br>* Other names: LMWH;|
| Active Comparator: Dalteparin group<br>Participants receive Dalteparin treatment daily -solution for subcutaneous injection | Drug: Dalteparin<br>* Dalteparin was administered via subcutaneous injection at a dose of 200 IU/kg (maximum daily dose 18,000 IU) for 30 days, and at a dose of 150 IU/kg from Day 31 to the end of treatment.<br>* Other names: Active comparator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adjudicated Recurrent Venous Thromboembolism (VTE) or Major Bleeding Event |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adjudicated Major Bleeding Events While on Treatment | The primary safety endpoint was major bleeding events during the On-Treatment Study Period (defined as on-study drug or up to 3 days after the last dose of study drug). | 12 months | 
| Number of Participants With Recurrent Venous Thromboembolism (VTE) During the Overall Study Period |  | 12 months | 
| Number of Participants With Recurrent Deep Vein Thrombosis (DVT) During the Overall Study Period |  | 12 months | 
| Number of Participants With Recurrent Non-Fatal Pulmonary Embolism (PE) During the Overall Study Period |  | 12 months | 
| Number of Participants With VTE-Related Death |  | 12 months | 
| Number of Participants With Recurrent VTE, Major Bleed or All-Cause Death |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Active Cancer with Metastasis