Trial Outcomes & Findings for Rivaroxaban With Diosmin in Long-term Treatment of Deep Vein Thrombosis (NCT NCT03413618)

NCT ID: NCT03413618

Last Updated: 2021-02-04

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 90 participants
• Primary outcome timeframe: 12 months
• Results posted on: 2021-02-04

Participant Flow

Admitted to the hospital with the suspicion for DVT: 202; DVT verified: 158; Eligible DVT: 102; Rejected to participate: 12; Randomized: 90

Participant milestones

Measure	Experimental: Rivaroxaban + Diosmin + Stockings treatment of DVT with anticoagulation (rivaroxaban), elastic compression stockings and additional prescription of diosmin Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month Diosmin: 600 mg q.d. for 12 month compression stockings: above knee stocking for 12 month	Control: Rivaroxaban + Stockings Only standard treatment of DVT with anticoagulation (rivaroxaban) and elastic compression stockings Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month compression stockings: above knee stocking for 12 month
Overall Study STARTED	45	45
Overall Study COMPLETED	45	45
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Experimental: Rivaroxaban + Diosmin + Stocking n=45 Participants treatment of DVT with anticoagulation (rivaroxaban), elastic compression stockings and additional prescription of diosmin Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month Diosmin: 600 mg q.d. for 12 month compression stockings: above knee stocking for 12 month	Control: Rivaroxaban + Stockings Only n=45 Participants standard treatment of DVT with anticoagulation (rivaroxaban) and elastic compression stockings Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month compression stockings: above knee stocking for 12 month	Total n=90 Participants Total of all reporting groups
Age, Continuous	57.4 years STANDARD_DEVIATION 13.8 • n=45 Participants	60.2 years STANDARD_DEVIATION 13.1 • n=45 Participants	58.8 years STANDARD_DEVIATION 13.4 • n=90 Participants
Sex: Female, Male Female	17 Participants n=45 Participants	17 Participants n=45 Participants	34 Participants n=90 Participants
Sex: Female, Male Male	28 Participants n=45 Participants	28 Participants n=45 Participants	56 Participants n=90 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Russia	45 participants n=45 Participants	45 participants n=45 Participants	90 participants n=90 Participants
Time to randomization	3.4 days STANDARD_DEVIATION 1.2 • n=45 Participants	3.5 days STANDARD_DEVIATION 1.6 • n=45 Participants	3.5 days STANDARD_DEVIATION 1.4 • n=90 Participants
Unprovoked DVT	29 Participants n=45 Participants	33 Participants n=45 Participants	62 Participants n=90 Participants
Preexisting chronic venous disease	23 Participants n=45 Participants	32 Participants n=45 Participants	55 Participants n=90 Participants
Thrombus burden	15.2 Marder score STANDARD_DEVIATION 4.7 • n=45 Participants	11.6 Marder score STANDARD_DEVIATION 4.1 • n=45 Participants	13.4 Marder score STANDARD_DEVIATION 4.7 • n=90 Participants

PRIMARY outcome

Timeframe: 12 months

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.

Outcome measures

Measure	Experimental: Rivaroxaban + Diosmin + Stockings n=45 Participants treatment of DVT with anticoagulation (rivaroxaban), elastic compression stockings and additional prescription of diosmin Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month Diosmin: 600 mg q.d. for 12 month compression stockings: above knee stocking for 12 month	Control: Rivaroxaban + Stockings Only n=45 Participants standard treatment of DVT with anticoagulation (rivaroxaban) and elastic compression stockings Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month compression stockings: above knee stocking for 12 month
Number of Participants With Postthrombotic Syndrome as Determined by Villalta Score	3 Participants	22 Participants

SECONDARY outcome

Timeframe: 12 months

detection of any episode of recurrent DVT with or without clinical signs verified by duplex ultrasound

Outcome measures

Measure	Experimental: Rivaroxaban + Diosmin + Stockings n=45 Participants treatment of DVT with anticoagulation (rivaroxaban), elastic compression stockings and additional prescription of diosmin Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month Diosmin: 600 mg q.d. for 12 month compression stockings: above knee stocking for 12 month	Control: Rivaroxaban + Stockings Only n=45 Participants standard treatment of DVT with anticoagulation (rivaroxaban) and elastic compression stockings Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month compression stockings: above knee stocking for 12 month
Number of Participants With Recurrent Symptomatic or Asymptomatic DVT	1 Participants	6 Participants

SECONDARY outcome

Timeframe: 12 months

detection of symptomatic pulmonary embolism verified with CT pulmonary angiogram

Outcome measures

Measure	Experimental: Rivaroxaban + Diosmin + Stockings n=45 Participants treatment of DVT with anticoagulation (rivaroxaban), elastic compression stockings and additional prescription of diosmin Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month Diosmin: 600 mg q.d. for 12 month compression stockings: above knee stocking for 12 month	Control: Rivaroxaban + Stockings Only n=45 Participants standard treatment of DVT with anticoagulation (rivaroxaban) and elastic compression stockings Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month compression stockings: above knee stocking for 12 month
Number of Participants With Symptomatic Pulmonary Embolism	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months

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)

Outcome measures

Measure	Experimental: Rivaroxaban + Diosmin + Stockings n=45 Participants treatment of DVT with anticoagulation (rivaroxaban), elastic compression stockings and additional prescription of diosmin Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month Diosmin: 600 mg q.d. for 12 month compression stockings: above knee stocking for 12 month	Control: Rivaroxaban + Stockings Only n=45 Participants standard treatment of DVT with anticoagulation (rivaroxaban) and elastic compression stockings Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month compression stockings: above knee stocking for 12 month
The Value of Venous Clinical Severity Score	1.2 VCSS score Standard Deviation 1.1	4.4 VCSS score Standard Deviation 2.1

SECONDARY outcome

Timeframe: 12 months

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.

Outcome measures

Measure	Experimental: Rivaroxaban + Diosmin + Stockings n=45 Participants treatment of DVT with anticoagulation (rivaroxaban), elastic compression stockings and additional prescription of diosmin Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month Diosmin: 600 mg q.d. for 12 month compression stockings: above knee stocking for 12 month	Control: Rivaroxaban + Stockings Only n=45 Participants standard treatment of DVT with anticoagulation (rivaroxaban) and elastic compression stockings Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month compression stockings: above knee stocking for 12 month
The Value of Chronic Lower Limb Venous Insufficiency Questionnaire - 20 Items	22.1 CIVIQ-20 scores Standard Deviation 3.3	28.8 CIVIQ-20 scores Standard Deviation 7.6

SECONDARY outcome

Timeframe: 12 months

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%.

Outcome measures

Measure	Experimental: Rivaroxaban + Diosmin + Stockings n=45 Participants treatment of DVT with anticoagulation (rivaroxaban), elastic compression stockings and additional prescription of diosmin Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month Diosmin: 600 mg q.d. for 12 month compression stockings: above knee stocking for 12 month	Control: Rivaroxaban + Stockings Only n=45 Participants standard treatment of DVT with anticoagulation (rivaroxaban) and elastic compression stockings Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month compression stockings: above knee stocking for 12 month
Number of Participants With Full Recanalization of the Popliteal Vein	42 Participants	28 Participants

SECONDARY outcome

Timeframe: 12 months

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).

Outcome measures

Measure	Experimental: Rivaroxaban + Diosmin + Stockings n=45 Participants treatment of DVT with anticoagulation (rivaroxaban), elastic compression stockings and additional prescription of diosmin Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month Diosmin: 600 mg q.d. for 12 month compression stockings: above knee stocking for 12 month	Control: Rivaroxaban + Stockings Only n=45 Participants standard treatment of DVT with anticoagulation (rivaroxaban) and elastic compression stockings Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month compression stockings: above knee stocking for 12 month
Extension of Residual Venous Obstruction by Marder Score	0.3 Marder score Standard Deviation 1.0	1.9 Marder score Standard Deviation 2.4

SECONDARY outcome

Timeframe: 12 months

any adverse events detected or suspected

Outcome measures

Measure	Experimental: Rivaroxaban + Diosmin + Stockings n=45 Participants treatment of DVT with anticoagulation (rivaroxaban), elastic compression stockings and additional prescription of diosmin Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month Diosmin: 600 mg q.d. for 12 month compression stockings: above knee stocking for 12 month	Control: Rivaroxaban + Stockings Only n=45 Participants standard treatment of DVT with anticoagulation (rivaroxaban) and elastic compression stockings Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month compression stockings: above knee stocking for 12 month
Adverse Events	5 Participants	4 Participants

SECONDARY outcome

Timeframe: 12 months

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

Outcome measures

Measure	Experimental: Rivaroxaban + Diosmin + Stockings n=45 Participants treatment of DVT with anticoagulation (rivaroxaban), elastic compression stockings and additional prescription of diosmin Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month Diosmin: 600 mg q.d. for 12 month compression stockings: above knee stocking for 12 month	Control: Rivaroxaban + Stockings Only n=45 Participants standard treatment of DVT with anticoagulation (rivaroxaban) and elastic compression stockings Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month compression stockings: above knee stocking for 12 month
Major Bleeding	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months

any non-major bleeding requiring anticoagulant withdrawal, and/or performing haemostatic measures, and/or hospitalization, and/or an unscheduled medical appointment

Outcome measures

Measure	Experimental: Rivaroxaban + Diosmin + Stockings n=45 Participants treatment of DVT with anticoagulation (rivaroxaban), elastic compression stockings and additional prescription of diosmin Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month Diosmin: 600 mg q.d. for 12 month compression stockings: above knee stocking for 12 month	Control: Rivaroxaban + Stockings Only n=45 Participants standard treatment of DVT with anticoagulation (rivaroxaban) and elastic compression stockings Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month compression stockings: above knee stocking for 12 month
Clinically Relevant Non-major Bleeding	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 12 months

any non-major or non-clinically relevant bleeding does not require the suspension of therapy and changes in the patient's lifestyle

Outcome measures

Measure	Experimental: Rivaroxaban + Diosmin + Stockings n=45 Participants treatment of DVT with anticoagulation (rivaroxaban), elastic compression stockings and additional prescription of diosmin Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month Diosmin: 600 mg q.d. for 12 month compression stockings: above knee stocking for 12 month	Control: Rivaroxaban + Stockings Only n=45 Participants standard treatment of DVT with anticoagulation (rivaroxaban) and elastic compression stockings Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month compression stockings: above knee stocking for 12 month
Minor Bleeding	2 Participants	2 Participants

Adverse Events

Study Group

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Control Group

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Study Group n=45 participants at risk treatment of DVT with anticoagulation (rivaroxaban), elastic compression stockings and additional prescription of diosmin Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month Diosmin: 600 mg q.d. for 12 month compression stockings: above knee stocking for 12 month	Control Group n=45 participants at risk standard treatment of DVT with anticoagulation (rivaroxaban) and elastic compression stockings Rivaroxaban: 15 mg b.i.d. for 3 weeks and then 20 mg q.d. up to 6 month compression stockings: above knee stocking for 12 month
Gastrointestinal disorders Dispesia	4.4% 2/45 • Number of events 2 • 12 months	0.00% 0/45 • 12 months
Blood and lymphatic system disorders Clinically relevant non-major bleeding	2.2% 1/45 • Number of events 1 • 12 months	4.4% 2/45 • Number of events 2 • 12 months
Blood and lymphatic system disorders Minor bleeding	4.4% 2/45 • Number of events 2 • 12 months	4.4% 2/45 • Number of events 2 • 12 months

Additional Information

Dr. Kirill Lobastov

Pirogov Russian National Research Medical University

Phone: +7-985-211-63-31

Email: lobastov_kv@hotmail.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place