Prophylactic Anticoagulation for Catheter-related Thrombosis

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.

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.

Study Overview

• Status: Unknown
• Conditions: Venous Thrombosis Due to Central Venous Access Device (Disorder); Prophylactic Anticoagulation; Patients With Tumor
• Intervention / Treatment: Drug: Aspirin 100mg; Drug: Rivaroxaban 10mg; Drug: low molecule heparin

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:

1. Age 18-75 years;
2. Patients with malignant tumors who received implantable drug delivery devices as intravenous access for systematic chemotherapy;
3. Eastern Cooperative Oncology Group (ECOG) class 0-1;
4. Expected to receive chemotherapy within 1 week of enrollment;
5. Expected survival of more than 6 months;
6. Ambulatory patients or outpatient chemotherapy patients whose intravenous chemotherapy less than 24 hours per hospital stay;
7. Khorana score 1-3 point.

Exclusion Criteria:

1. 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;
2. 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;
3. moderate to severe liver and kidney dysfunction;
4. pregnant or lactating women;
5. patients who are administered systemically with pyrrole-antimycotic agents (eg ketoconazole, itraconazole, voriconazole and posaconazole) or HIV protease inhibitors (eg ritonavir);
6. Patients taking methotrexate;
7. Patients with systemic use of non-steroidal anti-inflammatory drugs;
8. Patients who have had anticoagulant drugs for any other reason.

• Study Type: Interventional
• Enrollment (Anticipated): 1640
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jian Huang, Doctor; Phone Number: 13958123068; Email: hjys@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Dongyang, Zhejiang, China
      • Not yet recruiting
      • the People's Hospital of Dongyang City
      • Contact: Gui Nv Hu, Doctor
    • Hangzhou, Zhejiang, China
      • Not yet recruiting
      • The First Affiliated Hospital of Zhejiang University School of Medicine
      • Contact: Zhi Y Feng
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Second Affiliated Hospital, School of Medicine, Zhejiang University
      • Contact: Jian Huang, Doctor
    • Hangzhou, Zhejiang, China
      • Not yet recruiting
      • Sir Run Run Shaw Hospital, the Affiliated Hospital of Zhejiang University School of Medicine
      • Contact: Wen J Chen, Doctor
    • Hangzhou, Zhejiang, China
      • Not yet recruiting
      • the First People's Hospital of Xiaoshan District, Hangzhou
      • Contact: Zhen Y Wang, Doctor
    • Hangzhou, Zhejiang, China
      • Not yet recruiting
      • Women's Hospital of School of Medicine Zhejiang University
      • Contact: Jing P Long, Doctor
    • Hangzhou, Zhejiang, China
      • Not yet recruiting
      • Zhejiang Provincial Hospital of TCM
      • Contact: Gui P Chen, Doctor
    • Hangzhou, Zhejiang, China
      • Not yet recruiting
      • Zhejiang Provincial People's Hospital
      • Contact: Shi L Tu, Doctor
    • Huzhou, Zhejiang, China
      • Not yet recruiting
      • the Central Hospital of Huzhou City
      • Contact: Yun H Wei, Doctor
    • Jiaxing, Zhejiang, China
      • Not yet recruiting
      • the Second Affiliated Hospital of Jiaxing College
      • Contact: Shu Z Fang, Doctor
    • Jiaxing, Zhejiang, China
      • Not yet recruiting
      • the Women's Hospital of Jiaxing City
      • Contact: Juan Y Zhu, Doctor
    • Jinhua, Zhejiang, China
      • Not yet recruiting
      • the Central Hospital of Jinhua City
      • Contact: Shu G Li, Doctor
    • Lishui, Zhejiang, China
      • Not yet recruiting
      • The Central Hospital of Lishui City
      • Contact: Shu Z Chen, Doctor
    • Lishui, Zhejiang, China
      • Not yet recruiting
      • the People's Hospital of Jinyun County
      • Contact: Qing H Shen, Doctor
    • Lishui, Zhejiang, China
      • Not yet recruiting
      • the People's Hospital of Lishui City
      • Contact: Yi J Mei, Doctor
    • Lishui, Zhejiang, China
      • Not yet recruiting
      • the Women's Hospital of Lishui City
      • Contact: Jia M Lei, Doctor
    • Ningbo, Zhejiang, China
      • Not yet recruiting
      • the Affiliated Hospital of Ningbo University
      • Contact: Lv J Cen, Doctor
    • Ningbo, Zhejiang, China
      • Not yet recruiting
      • the Huamei Hospital of Ningbo City, University of Chinese Academy of Sciences
      • Contact: Yan Zhang, Doctor
    • Ningbo, Zhejiang, China
      • Not yet recruiting
      • the People's Hospital of Yinzhou
      • Contact: Ying J Wu, Doctor
    • Ningbo, Zhejiang, China
      • Not yet recruiting
      • the Women's and Children's Hospital of Ningbo City
      • Contact: Zhan W Li, Doctor
    • Shaoxing, Zhejiang, China
      • Not yet recruiting
      • The Affiliated Hospital of Shaoxing University
      • Contact: Jian Zhang, Doctor
    • Wenzhou, Zhejiang, China
      • Not yet recruiting
      • The Second Affiliated Hospital of Wenzhou Medical University
      • Contact: Min Zheng, Doctor
    • Wenzhou, Zhejiang, China
      • Not yet recruiting
      • The First Affiliated Hospital of Wenzhou Medical University
      • Contact: Ou C Wang, Doctor
    • Zhoushan, Zhejiang, China
      • Not yet recruiting
      • the Zhoushan Hospital of Zhejiang Province
      • Contact: Jing Xu, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. age 18-75 years;
2. patients with malignant tumors who received implantable drug delivery devices as intravenous access for systematic chemotherapy;
3. Eastern Cooperative Oncology Group (ECOG) class 0-1;
4. expected to receive chemotherapy within 1 week of enrollment;
5. expected survival of more than 6 months;
6. ambulatory patients or outpatient chemotherapy patients whose intravenous chemotherapy less than 24 hours per hospital stay;
7. Khorana score 1-3 point.

Exclusion Criteria:

1. 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;
2. 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;
3. moderate to severe liver and kidney dysfunction;
4. pregnant or lactating women;
5. patients who are administered systemically with pyrrole-antimycotic agents (eg ketoconazole, itraconazole, voriconazole and posaconazole) or HIV protease inhibitors (eg ritonavir);
6. patients taking methotrexate;
7. patients with systemic use of non-steroidal anti-inflammatory drugs;
8. patients who have had anticoagulant drugs for any other reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Aspirin 100mg	Drug: Aspirin 100mg; 100mg orally per day
EXPERIMENTAL: rivaroxaban 10mg	Drug: Rivaroxaban 10mg; 10mg orally per day
EXPERIMENTAL: low molecule heparin	Drug: low molecule heparin; 0.4ml per day subcutaneous injection
NO_INTERVENTION: Reference; 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

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Principal Investigator: Jian Huang, Doctor, Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2020
• Primary Completion (ANTICIPATED): August 30, 2021
• Study Completion (ANTICIPATED): February 28, 2022

Study Registration Dates

• First Submitted: January 12, 2020
• First Submitted That Met QC Criteria: February 4, 2020
• First Posted (ACTUAL): February 5, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 30, 2020
• Last Update Submitted That Met QC Criteria: June 26, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: cancer; anticoagulants; aspirin; rivaroxaban; thromboprophylaxis; implantable venous access ports; Catheter Related thrombosis; low molecule heparin
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Venous Thrombosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Aspirin; Rivaroxaban; Heparin
• Other Study ID Numbers: Research 2019-400

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No