Prophylactic Anticoagulation for Catheter-related Thrombosis

Study Overview
=================
Brief Summary
-----------------
The main objective of this study is to compare the efficacy and safety of aspirin, low molecule heparin and rivaroxaban for preventing catheter-related thrombosis in middle-to-high-risk ambulatory patients with cancer and implantable venous access ports.

Detailed Description
-----------------
Study Type: Interventional, randomized, parallel Assignment and no masking Study Arms & Intervention: Drug 1: Aspirin, 100mg/day orally; Drug 2: rivaroxaban, 10mg/day orally; Drug 3: low molecule heparin, 4000IU(0.4ml)/day subcutaneous injection; Reference: mechanical prophylaxis. Follow-up Period: 6 months. The trial visits occurred at time before each chemotherapy cycle. The following details should be included at each visit: Khorana score, height and weight, blood routine examination, coagulation function, stool-routine and occult blood test, renal and liver function, ultrasonography of both legs and neck. Primary Outcome: The primary efficacy end point was the occurrence of thrombus in the vein at the puncture site or nearby. The primary was the occurrence of a major bleeding event as defined by the International Society on Thrombosis and Haemostasis (ISTH). Secondary Outcome: The secondary efficacy end point was occurrence of occurrence of other thrombosis or embolism events like deep vein thrombosis or pulmonary embolism. The secondary safety endpoint was the occurrence of any clinically relevant non-major bleeding, minor bleeding and adverse events. Population: patients with cancer and implantable venous access ports Eligibility Criteria: Age 18-75 years; Patients with malignant tumors who received implantable drug delivery devices as intravenous access for systematic chemotherapy; Eastern Cooperative Oncology Group (ECOG) class 0-1; Expected to receive chemotherapy within 1 week of enrollment; Expected survival of more than 6 months; Ambulatory patients or outpatient chemotherapy patients whose intravenous chemotherapy less than 24 hours per hospital stay; Khorana score 1-3 point. Exclusion Criteria: Patients with a history of allergies to low molecular weight heparin, rivaroxaban, aspirin or other non-steroidal anti-inflammatory drugs, especially those with asthma, neurovascular edema or shock; Patients with bleeding risks: thrombocytopenia (platelet count < 50*109/L), clinically significant active bleeding, active gastric ulcer disease, severe arterial hypertension, history of previous stroke; moderate to severe liver and kidney dysfunction; pregnant or lactating women; patients who are administered systemically with pyrrole-antimycotic agents (eg ketoconazole, itraconazole, voriconazole and posaconazole) or HIV protease inhibitors (eg ritonavir); Patients taking methotrexate; Patients with systemic use of non-steroidal anti-inflammatory drugs; Patients who have had anticoagulant drugs for any other reason.

Official Title
-----------------
The Efficacy and Safety of Prophylactic Anticoagulation for Catheter-related Thrombosis in Patients With Cancer and Implantable Venous Access Ports: a Prospective Multi-center Randomized Controlled Trial.

Conditions
-----------------
Venous Thrombosis Due to Central Venous Access Device (Disorder), Prophylactic Anticoagulation, Patients With Tumor

Intervention / Treatment
-----------------
* Drug: Rivaroxaban 10mg
* Drug: Aspirin 100mg
* Drug: low molecule heparin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: age 18-75 years; patients with malignant tumors who received implantable drug delivery devices as intravenous access for systematic chemotherapy; Eastern Cooperative Oncology Group (ECOG) class 0-1; expected to receive chemotherapy within 1 week of enrollment; expected survival of more than 6 months; ambulatory patients or outpatient chemotherapy patients whose intravenous chemotherapy less than 24 hours per hospital stay; Khorana score 1-3 point. Exclusion Criteria: patients with a history of allergies to low molecular weight heparin, rivaroxaban, aspirin or other non-steroidal anti-inflammatory drugs, especially those with asthma, neurovascular edema or shock; patients with bleeding risks: thrombocytopenia (platelet count < 50*109/L), clinically significant active bleeding, active gastric ulcer disease, severe arterial hypertension, history of previous stroke; moderate to severe liver and kidney dysfunction; pregnant or lactating women; patients who are administered systemically with pyrrole-antimycotic agents (eg ketoconazole, itraconazole, voriconazole and posaconazole) or HIV protease inhibitors (eg ritonavir); patients taking methotrexate; patients with systemic use of non-steroidal anti-inflammatory drugs; patients who have had anticoagulant drugs for any other reason.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aspirin 100mg<br> | Drug: Aspirin 100mg<br>* 100mg orally per day<br>|
| Experimental: rivaroxaban 10mg<br> | Drug: Rivaroxaban 10mg<br>* 10mg orally per day<br>|
| Experimental: low molecule heparin<br> | Drug: low molecule heparin<br>* 0.4ml per day subcutaneous injection<br>|
| No Intervention: Reference<br>mechanical prophylaxis | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| occurrence of catheter-related thrombosis | detect the occurrence of catheter-related thrombosis with ultrasound, venography if necessary | from enrollment to the first time of occurrence of catheter-related thrombosis, up to 1 month after the completion of last chemotherapy cycle | 
| occurrence of major-bleeding event | define occurrence of major-bleeding event with ISTH standard | from enrollment to the first time of occurrence of major-bleeding event, up to 1 month after the completion of last chemotherapy cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| occurrence of other thrombosis or embolism events except for catheter-related thrombosis | detect deep vein thrombosis with ultrasound for the lower extremity, , ultrasound for the upper extremity, pulmonary arteriography or venography if necessary | from enrollment to the first time of occurrence of other thrombosis or embolism events except for catheter-related thrombosis , up to 1 month after the completion of last chemotherapy cycle | 
| occurrence of clinically relevant non-major-bleeding, minor-bleeding or non-bleeding event | define occurrence of non-major-bleeding or minor-bleeding event with ISTH standard, evaluate the relevant adverse drug reaction with NCI CTCAE 5.0 | from enrollment to the first time of occurrence of events, up to 1 month after the completion of last chemotherapy cycle | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
implantable venous access ports, Catheter Related thrombosis, thromboprophylaxis, anticoagulants, aspirin, low molecule heparin, rivaroxaban, cancer