Rivaroxaban With Diosmin in Long-term Treatment of Deep Vein Thrombosis (RIDILOTT-DVT)

The Efficacy of Rivaroxaban With Diosmin in the Long-term Treatment of Acute Proximal Deep Vein Thrombosis

The randomized clinical study aimed to assess the efficacy and safety of standard anticoagulation with rivaroxaban in combination with diosmin compared to the isolated use of standard rivaroxaban for prolonged therapy of acute femoro-popliteal deep vein thrombosis reflected the speed of deep vein recanalization and incidence of post-thrombotic syndrome.

Study Overview

• Status: Completed
• Conditions: Deep Vein Thrombosis; Postthrombotic Syndrome
• Intervention / Treatment: Drug: Rivaroxaban; Drug: Diosmin; Other: compression stockings

Detailed Description

Deep vein thrombosis is an acute inflammatory disease that affects vein wall and leads to the structural changes in the wall and valves reflected with chronic venous insufficiency that called postthrombotic syndrome (PTS).

Diosmin as a flavonoid agent has properties to reduce leukocyte-endothelial interaction and inflammatory response, that could reduce the damage to venous wall and valves.

The hypothesis of the study is based on assumption that diosmin combined with standard anticoagulation can improve outcomes of femoro-popliteal DVT due to increase speed of veins recanalization, decrease of vein wall inflammation and finally decrease the incidence of PTS at 6 month and 1 year after index DVT.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 4

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 121352
    • Clinical Hospital no.1 of the President's Administration of Russian Federation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age over 18 years
• The first episode of femoro-popliteal deep vein thrombosis (DVT)
• Verification of DVT by duplex ultrasound
• Informed consent signed

Exclusion Criteria:

• Suspicion of pulmonary embolism (PE)
• Verified PE
• Bilateral DVT
• Contraindications for rivaroxaban (in accordance with the official instructions)
• Contraindications for diosmin (in accordance with the official instructions)
• Active cancer
• Verified severe thrombophilia (antiphospholipid antibodies, deficiency of proteins C, S, antithrombin 3)
• Use of other anticoagulants for more than 7 days from the DVT verification
• Impossibility of using compression stocking after 3 days from DVT verification
• Performed surgical intervention on the superficial or deep veins of the lower extremities (thrombolysis, thrombectomy, vein ligation, implantation of the inferior cava filter)
• Continuous use of other drugs that affect the hemostasis system (except for acetylsalicylic acid in a dose of not more than 100 mg).
• Low compliance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Rivaroxaban + Diosmin + Stockings; treatment of deep vein thrombosis with anticoagulation (rivaroxaban), elastic compression stockings and additional prescription of diosmin	Drug: Rivaroxaban; 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month; Other Names: xarelto; Drug: Diosmin; 600 mg q.d. for 12 month; Other Names: flebodia; Other: compression stockings; above knee stocking for 12 month
Active Comparator: Control: Rivaroxaban + Stockings only; standard treatment of deep vein thrombosis with anticoagulation (rivaroxaban) and elastic compression stockings	Drug: Rivaroxaban; 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month; Other Names: xarelto; Other: compression stockings; above knee stocking for 12 month

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Postthrombotic Syndrome as Determined by Villalta Score	Detection of the postthrombotic syndrome (PTS) was made according to the Villalta score (a combination of 5 subjective symptoms and 6 objective signs of chronic venous disease) ranged from 0 (no signs) to 33 scores (maximal severity). PTS defined as 5 and more scores; mild PTS as 5-9 scores; moderate PTS as 10-14 scores; severe PTS as 15 and more scores.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Recurrent Symptomatic or Asymptomatic DVT	detection of any episode of recurrent DVT with or without clinical signs verified by duplex ultrasound	12 months
Number of Participants With Symptomatic Pulmonary Embolism	detection of symptomatic pulmonary embolism verified with CT pulmonary angiogram	12 months
The Value of Venous Clinical Severity Score	Venous Clinical Severity Score (VCSS) is a combination of subjective symptoms and objective signs of CVD aimed to assess the severity of disease and ranges from 0 (no signs and symptoms of CVD) to 30 (severe signs and symptoms of CVD)	12 months
The Value of Chronic Lower Limb Venous Insufficiency Questionnaire - 20 Items	Chronic Lower Limb Venous Insufficiency Questionnaire - 20 items (CIVIQ-20) is a venous specific questionnaire to assess the disease-specific quality of life (QoL). It contains 20 items of 1-5 scores, totally, from 20 (best QoL) to100 (worst QoL) scores.	12 months
Number of Participants With Full Recanalization of the Popliteal Vein	Full recanalization of popliteal vein suggests the residual venous obstruction (RVO) less than 20%. The RVO was assessed by duplex ultrasound and calculated as the vein cross-sectional diameter under the maximal compression divided on the diameter without any compression multiplied by 100%.	12 months
Extension of Residual Venous Obstruction by Marder Score	Residual venous obstruction (RVO) defined as a thrombotic masses occupying 20% and more of the vein cross-sectional diameter was measured by duplex ultrasound and calculated as the vein cross-sectional diameter under the maximal compression divided on the diameter without compression and multiplied by 100%. The extension of RVO was assessed by Marder score, the sum of all affected venous segments, evaluated by different scores (see Appendix of the Protocol), that ranged from 0 (no RVO) to 34 (RVO in all possible venous segments in one limb).	12 months
Adverse Events	any adverse events detected or suspected	12 months
Major Bleeding	according to the International Society of Thrombosis and Hemostasis (ISTH) definition, major bleeding defined as fatal bleeding, and/or symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome, and/or bleeding causing a fall in hemoglobin level of 20 g/L or 1.24 mmol/L or more, or leading to transfusion of two or more units of whole blood or red cells	12 months
Clinically Relevant Non-major Bleeding	any non-major bleeding requiring anticoagulant withdrawal, and/or performing haemostatic measures, and/or hospitalization, and/or an unscheduled medical appointment	12 months
Minor Bleeding	any non-major or non-clinically relevant bleeding does not require the suspension of therapy and changes in the patient's lifestyle	12 months

Collaborators and Investigators

• Sponsor: Pirogov Russian National Research Medical University
• Investigators: Principal Investigator: Ilya Schastlivtsev, PhD, Pirogov Russian National Research Medical University

Publications and helpful links

General Publications

• Lobastov K, Sautina E, Alencheva E, Bargandzhiya A, Schastlivtsev I, Barinov V, Laberko L, Rodoman G, Boyarintsev V. Intermittent Pneumatic Compression in Addition to Standard Prophylaxis of Postoperative Venous Thromboembolism in Extremely High-risk Patients (IPC SUPER): A Randomized Controlled Trial. Ann Surg. 2021 Jul 1;274(1):63-69. doi: 10.1097/SLA.0000000000004556.

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2017
• Primary Completion (Actual): July 31, 2019
• Study Completion (Actual): July 31, 2019

Study Registration Dates

• First Submitted: January 18, 2018
• First Submitted That Met QC Criteria: January 26, 2018
• First Posted (Actual): January 29, 2018

Study Record Updates

• Last Update Posted (Actual): February 4, 2021
• Last Update Submitted That Met QC Criteria: January 14, 2021
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: treatment; prevention; anticoagulation; deep vein thrombosis; postthrombotic syndrome
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Peripheral Vascular Diseases; Venous Insufficiency; Phlebitis; Thrombosis; Venous Thrombosis; Postthrombotic Syndrome; Postphlebitic Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban
• Other Study ID Numbers: RIDILOTT-DVT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No