Rivaroxaban for the Prevention of Deep Vein Thrombosis in Patients With Left Iliac Vein Compression - The PLICTS Study (PLICTS)

An Efficacy and Safety Study of Rivaroxaban for the Prevention of Deep Vein Thrombosis in Patients With Left Iliac Vein Compression Treated With Stent Implantation (PLICTS)：A Prospective Randomized Controlled Trial

The purpose of this study is to evaluate the efficacy and safety of rivaroxaban for the prevention of deep vein thrombosis in patients with left iliac vein compression treated with stent implantation.

Study Overview

• Status: Recruiting
• Conditions: May-Thurner Syndrome
• Intervention / Treatment: Drug: Rivaroxaban; Drug: Warfarin; Drug: Nadroparin

Detailed Description

Left Iliac Vein Compression Syndrome (LIVCS) is a disease of iliac vein stenosis/occlusion caused by chronic friction and compression of the left iliac vein by the right common iliac artery and lumbar vertebra. It is also called Cockett syndrome or May-Thurner syndrome. Recently, left iliac vein balloon dilatation with stent implantation have been used to treat patients with LIVCS, and have achieved good results. However, no matter the iliac vein stenosis or occlusion, interventional therapy can directly cause local trauma and intimal injury, which is a clear inducement of local thrombosis. Therefore, high intensity anticoagulation therapy is still needed to prevent secondary thrombosis in stent after left iliac vein balloon dilatation with stent implantation. At present, the postoperative anticoagulation regimen of these patients is early heparin anticoagulant therapy, and later warfarin anticoagulant therapy. However, due to the narrow therapeutic window of the drug, patients need to adjust the dosage according to coagulation function under the guidance of doctors. Rivaroxaban can simplify treatment, and is safe. Previous studies have shown that rivaroxaban is effective in preventing deep venous thrombosis after orthopaedic surgery. Rivaroxaban has also been shown to be safe and effective in anticoagulation therapy for patients with deep venous thrombosis and pulmonary embolism. However, Rivaroxaban lacks sufficient clinical data for adjuvant anticoagulation therapy after balloon dilatation with stent implantation. Therefore, this study should be carried out to provide the basis for LIVCS treatment guidelines and explore the clinical indications of rivaroxaban.

• Study Type: Interventional
• Enrollment (Estimated): 224
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Li Yin; Phone Number: 86-0571-87913706; Email: lawson4001@zju.edu.cn

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230000
      • Recruiting
      • Anhui Provincial Hospital
      • Contact: Zhengdong Fang; Phone Number: 86 15256990126; Email: fangzhengdong@126.com
  • Shangdong
    • Yantai, Shangdong, China, 264000
      • Recruiting
      • Yantai Yuhuangding Hospital
      • Contact: Lubin Li, MD; Phone Number: 86 18653587255; Email: 278468192@qq.com
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Huadong Hospital Affiliated to Fudan University
      • Contact: Wan Zhang, MD,PhD; Phone Number: 86 13916056910; Email: ant0930@163.com
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Shanghai 5th People's Hospital
      • Contact: Bin Gao, MD,PhD; Phone Number: 86 13764979078; Email: doctorgaobin@163.com
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Zhongshan Hospital Affiliated to Fudan University
      • Contact: Jianing Yue, MD,PhD; Phone Number: 86 13564788422; Email: yuejianing@gmail.com
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Zhejiang Provincial People's Hospital
      • Contact: Guangwei Yang; Phone Number: 13758146564; Email: ygw_zju@126.com
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • Sir Run Run Shaw Hospital
      • Contact: Yuefeng Zhu, MD; Phone Number: 86 13868101010; Email: drzyf@hotmail.com
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The Second Affiliated Hospital of Zhejiang University School of Medicine
      • Contact: Zhejie Liu, MD,PhD; Phone Number: 86 15268135830; Email: lawson3001@gmail.com
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Zhejiang Xiaoshan Hospital
      • Contact: Wei Han; Phone Number: 18957113906; Email: hw9453@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with thrombotic left iliac vein compression syndrome who underwent left iliac vein stent implantation

Exclusion Criteria:

• Age < 18 years or age > 75 years
• With history of pelvic surgery, left iliac vein trauma and pelvic radiotherapy
• With obvious contraindications for anticoagulation therapy
• Allergic to iodine contrast agents in the past
• With concomitant diseases that need high-intensity anticoagulation, and the anticoagulation intensity is clearly higher than that of the patients with iliac vein therapy alone
• Active bleeding or potential bleeding risk
• Pregnant or breastfeeding women
• With pelvic tumors causing compression of left iliac vein,
• With chronic venous insufficiency of lower extremities caused by K-T syndrome
• With malignant tumors and life expectancy < 1 year
• Taking cytochrome P450 3A4(CYP-450 3A4) inhibitors or inducers

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rivaroxaban; Participants will receive rivaroxaban 15mg twice daily for three weeks, then 20mg oral once daily after operation.	Drug: Rivaroxaban; Dose: 15mg twice daily for three weeks, then 20mg once daily until six months after the operation. Application: oral; Other Names: Xarelto
Active Comparator: Warfarin/Nadroparin; Participants will receive nadroparin 1mg/kg twice daily (subcutaneous), plus warfarin 3mg oral once daily for 5 days after the operation, later warfarin(oral) at individually titrated doses(0.75mg to 18mg) to achieve a target international normalized ratio (INR) of 2.0 to 3.0, once daily until 6 months.	Drug: Warfarin; Dose: 3mg for 5 days after the operation, later 0.75mg to 18mg depending on INR (2.0-3.0) until 6 months Duration: 6 months Frequency: once daily Application: oral; Other Names: coumadin; Drug: Nadroparin; Dose: 1mg/kg Duration: 5 days after the operation Frequency: twice daily Application: subcutaneous; Other Names: Fraxiparin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
stent occlusion rate	Stent occlusion is defined as DS > 50% for each modality with no procedure performed on the treated segment	2 year after operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life Change Scale Survey Results	Quality of life will be assessed by MOS item short-form health survey scale (SF-36). SF-36 includes eight subscales: physical functioning (PF, 10 items), role limitations due to physical health problems (RL-P, 4 items), bodily pain (BP, 2 items), general health (GH, 5 items), vitality (V, 4 items), social functioning (SF, 2 items), role limitations due to emotional problems (RL-E, 3 items) and mental health (MH, 5 items). The vitality sub-score assesses energy and fatigue, and ranges from 0 (worst) - 100 (best).	1, 3, 6, 12, 18 and 24 months after operation
All cause mortality	Percentage of participants with all deaths	1, 3, 6, 12, 18 and 24 months after operation
anticoagulation raleted mortality	Percentage of participants with anticoagulation raleted deaths	1, 3, 6, 12, 18 and 24 months after operation
Proportion of participants with stent displacement/fracture	Events will be assessed based on computed tomography (CT) or X ray	1, 3, 6, 12, 18 and 24 months after operation
Proportion of participants with hemorrhage	Including hemorrhagic stroke, gastrointestinal bleeding, hematuria, mucocutaneous hemorrhage and other visceral bleeding	1, 3, 6, 12, 18 and 24 months after operation
Proportion of participants with other vascular events	All vascular events (ST segment elevation myocardial infarction, non ST segment elevation myocardial infarction, acute coronary syndrome, unstable angina, ischemic stroke, transient ischemic attack, pulmonary embolism, non-central nervous system systemic embolism or vascular death) will be assessed based results/films/images of confirmatory testing, and/or case summaries.	1, 3, 6, 12, 18 and 24 months after operation
Proportion of participants with thrombosis		1, 3, 6, 12, 18 and 24 months after operation

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: Shanghai Zhongshan Hospital; Sir Run Run Shaw Hospital; Zhejiang Provincial People's Hospital; Anhui Provincial Hospital; Yantai Yuhuangding Hospital; Huadong Hospital; Shanghai 5th People's Hospital; Zhejiang Hospital
• Investigators: Principal Investigator: Zhejie Liu, MD,PhD, Second Affiliated Hospital, School of Medicine, Zhejiang University

Publications and helpful links

General Publications

• Liu Z, Gao N, Shen L, Yang J, Zhu Y, Li Z, Si Y. Endovascular treatment for symptomatic iliac vein compression syndrome: a prospective consecutive series of 48 patients. Ann Vasc Surg. 2014 Apr;28(3):695-704. doi: 10.1016/j.avsg.2013.05.019. Epub 2013 Oct 27.
• O'Sullivan GJ, Semba CP, Bittner CA, Kee ST, Razavi MK, Sze DY, Dake MD. Endovascular management of iliac vein compression (May-Thurner) syndrome. J Vasc Interv Radiol. 2000 Jul-Aug;11(7):823-36. doi: 10.1016/s1051-0443(07)61796-5.
• Hurst DR, Forauer AR, Bloom JR, Greenfield LJ, Wakefield TW, Williams DM. Diagnosis and endovascular treatment of iliocaval compression syndrome. J Vasc Surg. 2001 Jul;34(1):106-13. doi: 10.1067/mva.2001.114213.
• Eriksson BI, Kakkar AK, Turpie AG, Gent M, Bandel TJ, Homering M, Misselwitz F, Lassen MR. Oral rivaroxaban for the prevention of symptomatic venous thromboembolism after elective hip and knee replacement. J Bone Joint Surg Br. 2009 May;91(5):636-44. doi: 10.1302/0301-620X.91B5.21691. Erratum In: J Bone Joint Surg Br. 2009 Aug;91(8):1120.
• Li M, Zhang L, Zhang K, Zhu Y, Shi Z, Zhang W, Gao B, Li L, Fang Z, Yin L, Chen B, Liu Z. An efficacy and safety study of rivaroxaban for the prevention of deep vein thrombosis in patients with left iliac vein compression treated with stent implantation (PLICTS): study protocol for a prospective randomized controlled trial. Trials. 2020 Sep 29;21(1):811. doi: 10.1186/s13063-020-04742-z.
• Turpie AG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM, Cushner FD, Lotke PA, Berkowitz SD, Bandel TJ, Benson A, Misselwitz F, Fisher WD; RECORD4 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009 May 16;373(9676):1673-80. doi: 10.1016/S0140-6736(09)60734-0. Epub 2009 May 4. Erratum In: Lancet. 2022 Dec 10;400(10368):2048.

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2020
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: July 24, 2019
• First Submitted That Met QC Criteria: August 22, 2019
• First Posted (Actual): August 26, 2019

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: warfarin; rivaroxaban; stent implantation; May-Thurner Syndrome
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Congenital Abnormalities; Embolism and Thrombosis; Cardiovascular Abnormalities; Vascular Malformations; Peripheral Vascular Diseases; Thrombosis; Venous Thrombosis; May-Thurner Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Warfarin; Nadroparin
• Other Study ID Numbers: SAHZhejiangU-001

Drug and device information, study documents

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