Edoxaban for the Treatment of Coagulopathy in Patients With Active Cancer and Acute Ischemic Stroke: a Pilot Study. (ENCHASE Study)

Study Overview
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Brief Summary
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Purpose: Cancer-related hypercoagulability plays an important role in the development of cancer-related stroke. With rapidly aging population and increasing cancer prevalence, cancer related stroke has become an important stroke subtype. Recent studies suggest that hypercoagulability is associated with poor prognosis and effective correction of coagulopathy maybe protective for survival in cancer related stroke patients. Optimal strategies to correct coagulopathy in cancer stroke patient remains to be determined. Currently, the use of low molecular-weighted heparin is recommended in these patients, but non-vitamin K oral anticoagulants (NOACs) could be safe alternative without the need for injection subcutaneously. Furthermore, NOACs could be an optimal treatment strategy for cancer-related stroke in terms of correcting coagulopathy with less injection related complication (ex. pain and infection) compared to Enoxaparin.

Official Title
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Edoxaban for the Treatment of Coagulopathy in Patients With Active Cancer and Acute Ischemic Stroke: a Pilot Study. (ENCHASE Study)

Conditions
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Correction of Cancer-related Coagulopathy With Novel Oral Anticoagulant (Edoxaban)

Intervention / Treatment
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* Drug: Edoxaban
* Drug: Enoxaparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults over 20 years old Acute cerebral infarction within 30 days of symptom onset was confirmed by diffusion-weighted brain magnetic resonance imaging (DWI) Cancer-related stroke, not diagnosed with other classic (arteriosclerosis, cardioembolicm, small-vessel occlusion, etc.) cerebral infarction, within six months of diagnosis, chemotherapy, surgery for cancer. with informed consent from the patient or next-of-kin, When the subject becomes able to decide whether to participate in the study, the researcher acquires further consent directly from the subject. Exclusion Criteria: Patients with primary intracranial malignancy Patients with classic causes of cerebral infarction Patients with infectious or immunological disease that may affect blood D-dimer levels Patients whose cerebral infarction is thought to be caused by tumor (vascular occlusion due to tumor tissue) Patients who can not use anticoagulants with thrombocytopenia (platelet <50,000), anemia (hemoglobin <8) Decreased renal function (creatine clearance <15 mL / mim) Patients who received intravenous tissue plasminogen activator Patients with uncontrolled severe hypertension Patients who received prosthetic heart valve replacement requiring anticoagulation Patients with moderate to severe mitral stenosis Pulmonary embolism requiring hemodynamically unstable or thrombolysis or pulmonary embolization Pregnant and lactating women Patients who are hypersensitive to the major component or constituent of the test drug Patients with liver diseases associated with blood clotting disorders and clinically significant bleeding risks

Ages Eligible for Study
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Minimum Age: 20 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>Edoxaban, per oral, 60mg qd (may consider reduced dose to 30mg qd in patients with proper clinical reason by attending physician, estimated creatinine clearance of 30 to 50 ml per minute, a body weight of 60 kg or less, or the concomitant use of verapamil or quinidine), for 90 days. | Drug: Edoxaban<br>* Edoxaban, per oral, 60mg qd (may consider reduced dose to 30mg qd in patients with proper clinical reason by attending physician, estimated creatinine clearance of 30 to 50 ml per minute, a body weight of 60 kg or less, or the concomitant use of verapamil or quinidine), for 90 days.<br>|
| Active Comparator: Enoxaparin group<br>Enoxaparin, subcutaneous injection, 1mg/kg BID (may consider reduced dose to 1mg/kg qd in patients with proper clinical reason by attending physician, Creatinine clearance <30 mL/min), for 90 days. | Drug: Enoxaparin<br>* Enoxaparin, subcutaneous injection, 1mg/kg BID (may consider reduced dose to 1mg/kg qd in patients with proper clinical reason by attending physician, Creatinine clearance <30 mL/min), for 90 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| D-dimer change | interval change of serum D-dimer level between day 0 and 7 | 7 days after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Surrogate endpoint | number of micro-embolic signal detected by transcranial doppler | 7 days after treatment | 
| Functional outcome | modified Rankin scale at 90 days, from 0 to 6, higher is worse | 90 days after enrollment | 
| Incidence of Treatment-Emergent Adverse Events [symptomatic intracerebral hemorrhage] | symptomatic intracerebral hemorrhage major bleeding all-cause death | 90 days after enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer-related stroke, coagulopathy, D-dimer, Edoxaban, enoxaparine