Superficial Vein Thrombosis (SVT) Treated With Rivaroxaban Versus Fondaparinux

Superficial Vein Thrombosis (SVT) Treated for Forty-five Days With Rivaroxaban Versus Fondaparinux

The purpose of this study is to evaluate the efficacy and safety of rivaroxaban versus fondaparinux in the treatment of superficial vein thrombosis (SVT).

Study Overview

• Status: Completed
• Conditions: Superficial Vein Thrombosis
• Intervention / Treatment: Drug: Rivaroxaban; Drug: Fondaparinux

Detailed Description

Evaluation of efficacy and safety of 45 days of rivaroxaban 10 mg vs. fondaparinux 2.5 mg in the treatment of superficial vein thrombosis of risk patients for major VTE complications to prove non-inferiority of oral rivaroxaban treatment

• Study Type: Interventional
• Enrollment (Actual): 472
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10787
    • Franziskus-Krankenhaus Berlin
  • Berlin, Germany, 12043
    • MVZ Ramdohr, Praxis für Cardiovaskulär- u. Ultraschalldiagnostik
  • Berlin, Germany, 12627
    • Praxis für Chirurgie & Gefäßmedizin
  • Darmstadt, Germany, 64283
    • Klinikum Darmstadt GmbH
  • Eschwege, Germany, 37269
    • Gemeinschaftspraxis Eggeling und Winter
  • Hamburg, Germany, 22559
    • Asklepios Westklinikum Hamburg
  • Heidelberg, Germany, 69120
    • Universitatsklinikum Heidelberg
  • Hoppegarten, Germany, 15366
    • Internistische Praxisgemeinschaft
  • Karlsbach, Germany, 76307
    • Akademie für Gefäßkrankheiten e.V.
  • Köln, Germany, 50670
    • Praxis für Allgemeinmedizin und Phlebologie
  • Leipzig, Germany
    • Universitätsklinikum Leipzig AöR Innere Medizin - Angiologische Ambulanz
  • Lübeck, Germany, 23538
    • Universitätsklinikum Schleswig-Holstein, Campus Lübeck
  • Magdeburg, Germany, 39112
    • Praxis Dr. Franke
  • Mühldorf Am Inn, Germany, 84453
    • Kardiologie Mühldorf am Inn
  • Rostock, Germany, 18059
    • Praxis Dr. Kähler
  • Rottach-Egern, Germany, 83700
    • Praxis für Gefäßmedizin am Tegernsee
  • Wiesbaden, Germany, 65183
    • Venenzentrum Wiesbaden
  • Baden-Württemberg
    • Freiburg, Baden-Württemberg, Germany, 79098
      • Hautarztpraxis
  • Bayern
    • München, Bayern, Germany, 80331
      • Gemeinschaftspraxis Mietaschk, Bilderling, Kaiser, Tato
  • Nordrhein-Westfalen
    • Baesweiler, Nordrhein-Westfalen, Germany, 52499
      • Chriurgische Praxisklinik
  • Sachsen
    • Dresden, Sachsen, Germany, 01067
      • Krankenhaus Dresden-Friedrichstadt
    • Dresden, Sachsen, Germany, 01307
      • Universitätsklinikum Dresden
    • Görlitz, Sachsen, Germany, 02826
      • Oberlausitz-Gefäßpraxis

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• acute symptomatic supragenual superficial vein thrombosis of the leg
• at least one of the following major risk factor for VTE:
• age > 65 years or
• male sex or
• history of DVT/PE/SVT or
• history of cancer or active cancer or
• autoimmune disease or
• SVT of a non-varicose vein
• thrombus extension of at least 5 cm
• proximal thrombus end with more than 3 cm distance to the saphenofemoral junction (SFJ)
• age > 18 years
• written informed consent

Exclusion Criteria:

• other indication for therapeutic anticoagulation such as acute deep vein thrombosis, acute pulmonary embolism, atrial fibrillation with indication for anticoagulant therapy
• any PE or DVT within last 6 months before inclusion
• clinical signs of PE without objective exclusion (CT or VQ scan, angiography)
• SVT without signs of thrombotic/inflammatory activity (activity signs: diameter > 4 mm, pain, redness, elevated local or systemic temperature)
• SVT after sclerotherapy
• Duration of symptoms > 3 weeks
• pretreatment of more than 72 h with therapeutic dosages of oral or parenteral anticoagulants
• pretreatment of more than 5 days with subtherapeutic oral or parenteral anticoagulants
• indication for escalated antiplatelet therapy (monotherapy with aspirin > 325 g/d and any dual antiplatelet therapy)
• SVT closer than 3 cm to saphenofemoral junction (SVJ)
• anticipated superficial vein surgery within 90 days
• anticipated thrombolytic therapy within 90 days
• manifest clinically relevant bleeding
• clinically relevant bleeding in the last 30 days before study inclusion
• major surgery within last 30 days before inclusion
• ophthalmic, spinal or cerebral surgery within last 90 days
• severe head trauma within last 90 days
• hemorrhagic stroke within last 12 months
• hereditary or acquired severe hemorrhagic diathesis
• gastrointestinal bleeding within last 90 days requiring endoscopy
• uncontrolled arterial hypertension (systolic > 180 mm Hg, diastolic > 110 mm Hg)
• acute endocarditis
• low platelet count (< 100 x 109/l)
• Prothrombin time < 50 %
• calculated creatinine clearance < 30 ml/min
• significant liver disease such as acute hepatitis, chronic active hepatitis, cirrhosis
• life expectancy < 3 months
• any contraindications listed for rivaroxaban or fondaparinux
• women of child bearing potential without safe contraception method
• pregnant or breastfeeding women
• participation in another trial with pharmacological intervention

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; Rivaroxaban for 45 days oral dose: 10 mg OD	Drug: Rivaroxaban; Dose: 10 mg Duration: 45 (±5) days Frequency: once daily Application: oral; Other Names: Xarelto
Active Comparator: Fondaparinux; Fondaparinux for 45 days subcutaneous application: 2,5 mg OD	Drug: Fondaparinux; Fondaparinux Dose: 2.5 mg Duration: 45 (±5) days Frequency: once daily Application: subcutaneous; Other Names: Arixtra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Objectively Confirmed VTE Complications	The primary efficacy outcome was the composite of death from any cause, symptomatic pulmonary embolism (confirmed by ventilation-perfusion scanning, helical computed tomography, pulmonary angiography, or autopsy), symptomatic deep vein thrombosis (confirmed by ultrasonography or venography), or symptomatic extension towards the saphenofemoral junction or symptomatic recurrence of superficial vein thrombosis (confirmed by ultrasonography) up to day 45.	45 +/- 5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Primary Efficacy Outcome	For this, secondary efficacy outcomes were the composite primary efficacy outcome up to Day 90 and the following outcomes up to Day 45 and Day 90: each component of the primary efficacy outcome, the rate of major VTE (composite of symptomatic pulmonary embolism or symptomatic proximal DVT or VTE-related death) and the rates of surgery for SVT.	90 +/- 10 days
Rate of Major VTE	composite of: symptomatic pulmonary embolism; symptomatic proximal DVT; VTE-related death	90 +/-10 days
Rates of Surgery for SVT		90 +/-10 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Bleeding (Main Safety Outcome)	associated with a fall of hemoglobin of 2 g/l or more, or;; leading to a transfusion of 2 or more units of packed red blood cells or whole blood, or;; occurring into a critical site such as intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, retroperitoneal, or;; fatal bleeding.	45 +/- 5 days
Clinically Relevant Non-major, Minor and Total (Any) Bleeding	Clinically relevant, non-major bleeding is defined as any overt bleeding and; associated with a medical intervention, or; unscheduled contact with the physician (presence or telephone contact); temporary or complete cessation of study drug; associated with any relevant discomfort to the patient (pain, impairment of activities of daily life)	45 +/- 5 days

Collaborators and Investigators

• Sponsor: GWT-TUD GmbH
• Collaborators: Bayer
• Investigators: Principal Investigator: Jan Beyer-Westendorf, MD, on behalf of GWT-TUD GmbH

Publications and helpful links

General Publications

• Kearon C, Carrier M, Gu CS, Schulman S, Bates SM, Kahn SR, Chagnon I, Nguyen DT, Wu C, Rudd-Scott L, Julian JA. Rivaroxaban Compared to Placebo for the Treatment of Leg Superficial Vein Thrombosis: A Randomized Trial. Semin Thromb Hemost. 2020 Nov;46(8):977-985. doi: 10.1055/s-0040-1718891. Epub 2020 Dec 23.
• Beyer-Westendorf J, Schellong SM, Gerlach H, Rabe E, Weitz JI, Jersemann K, Sahin K, Bauersachs R; SURPRISE investigators. Prevention of thromboembolic complications in patients with superficial-vein thrombosis given rivaroxaban or fondaparinux: the open-label, randomised, non-inferiority SURPRISE phase 3b trial. Lancet Haematol. 2017 Mar;4(3):e105-e113. doi: 10.1016/S2352-3026(17)30014-5. Epub 2017 Feb 16.
• Werth S, Bauersachs R, Gerlach H, Rabe E, Schellong S, Beyer-Westendorf J. Superficial vein thrombosis treated for 45 days with rivaroxaban versus fondaparinux: rationale and design of the SURPRISE trial. J Thromb Thrombolysis. 2016 Aug;42(2):197-204. doi: 10.1007/s11239-016-1354-3.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: December 19, 2011
• First Submitted That Met QC Criteria: December 21, 2011
• First Posted (Estimate): December 26, 2011

Study Record Updates

• Last Update Posted (Actual): May 15, 2023
• Last Update Submitted That Met QC Criteria: July 18, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: thrombosis; SVT; superficial vein thrombosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Venous Thrombosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Fondaparinux; PENTA
• Other Study ID Numbers: SURPRISE-2011