A Phase 3b, prospective, randomized, open-label, blind evaluator (PROBE) study evaluating the efficacy and safety of LMWheparin/edoxaban versus dalteparin in venous thromboembolism associated with cancer

Phase 3

Completed

Conditions: deep vein thrombosis-pulmonary embolism
venous thromboembolism
10014523

Registration Number: NL-OMON45054

Lead Sponsor: Daiichi Sankyo, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 174

Inclusion Criteria

Inclusion Criteria:
1. Male or female subjects with age * 18 years or the otherwise legal lower age according to the country of residence;
2. Confirmed symptomatic or unsuspected lower extremity proximal DVT (ie, popliteal, femoral, iliac or inferior vena cava vein thrombosis), or confirmed symptomatic PE, or unsuspected PE of a segmental or larger pulmonary artery;
3. Cancer, other than basal-cell or squamous-cell carcinoma of the skin. Cancer should be active (see Section 6.1) or diagnosed within 2 years prior to randomization. The diagnosis/history of cancer must be objectively documented;
4. Intention for long-term treatment (at least 6 months) with parenteral LMWH;
5. Able to provide written informed consent.

Exclusion Criteria

1. Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current (index) episode of DVT and/or PE;
2. More than 72 hours pre-treatment with therapeutic dosages of anticoagulant treatment (LMWH, unfractionated heparin, and fondaparinux per local labeling), oral direct anticoagulants or vitamin K antagonist (VKA) prior to randomization to treat the current (index) episode;
3. Treatment with therapeutic doses of an anticoagulant including dalteparin for an indication other than VTE prior to randomization;
4. Active bleeding or any contraindication for treatment with LMWH/dalteparin or edoxaban;
5. Indication for dalteparin other than DVT and/or PE;
6. An Eastern Cooperative Oncology Group (ECOG) Performance Status of 3 or 4 at the time of randomization (see Appendix 17.6);
7. Calculated creatinine clearance (CrCL) < 30 mL/min;
8. History of heparin associated thrombocytopenia;
9. Acute hepatitis, chronic active hepatitis, liver cirrhosis;
10. Hepatocellular injury with concurrent transaminase (alanine transaminase [ALT]/aspartate transaminase [AST] > 3 x upper limit of normal [ULN]) and bilirubin (> 2 x ULN) elevations in the absence of a clinical explanation;
11. Life expectancy < 3 months;
12. Platelet count < 50,000/mL;
13. Uncontrolled hypertension as judged by the Investigator (eg, systolic blood pressure > 170 mmHg or diastolic blood pressure > 100 mmHg despite antihypertensive treatment);
14. Women of childbearing potential without proper contraceptive measures, and women who are pregnant or breast feeding;
15. Chronic treatment with non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) including both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) inhibitors for * 4 days/week anticipated to continue during the study;
16. Treatment with aspirin in a dosage of more than 100 mg/per day or dual antiplatelet therapy (any 2 antiplatelet agents including aspirin plus any other oral or intravenous antiplatelet drug) anticipated to continue during the study;
17. Systemic use of the P-gp inhibitors ketoconazole, itraconazole, erythromycin, azithromycin or clarithromycin at the time of randomization; subsequent use is permitted (with appropriate dose reduction of edoxaban);
18. Subjects with any condition that as judged by the Investigator would place the subject at increased risk of harm if he/she participated in the study.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary study outcome is the composite of recurrent VTE, and major bleeding.<br /><br>Recurrent VTE is either:<br /><br>* symptomatic confirmed (new) DVT or (new) PE;<br /><br>* unsuspected (new) proximal DVT of the legs or unsuspected (new) PE located in<br /><br>segmental or more proximal arteries:<br /><br>* Unsuspected DVT or PE are thrombi that are detected during imaging testing<br /><br>performed for other reasons (eg, computed tomography (CT) for cancer staging)<br /><br>and not for suspicion of DVT or PE.<br /><br>* fatal PE (including unexplained death for which PE cannot be ruled out). </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary Outcomes:<br /><br>* Recurrent VTE;<br /><br>* Major bleeding;<br /><br>* CRNM bleeding;<br /><br>* Major + CRNM bleeding;<br /><br>* All bleedings;<br /><br>* Event-free survival, defined as the proportion of subjects over time free of<br /><br>recurrent VTE, major bleeding events, and death;<br /><br>* VTE-related death;<br /><br>* Mortality from all causes;<br /><br>* Recurrent DVT;<br /><br>* Recurrent PE;<br /><br>* Healthcare resource utilization for potential recurrent VTE and bleed events.<br /><br>Other outcomes include:<br /><br>* Cardiovascular events (MI, stroke, SEE ;<br /><br>* Thrombotic events at other locations ;<br /><br>* Reason for permanent early discontinuation of study drug.</p><br>