Venous Thromboembolism (VTE) Treatment Study in Japanese Deep Vein Thrombosis (DVT) Patients

Randomized, Open-label (Double Blind Among Rivaroxaban Groups in the Initial 3 Weeks), Parallel-group, Active-controlled Study of Rivaroxaban in Patients With Acute Symptomatic Deep Vein Thrombosis Without Symptomatic Pulmonary Embolism

The objective of this study is to evaluate the efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of two different dosages of rivaroxaban in the treatment of deep vein thrombosis (DVT) and the prevention of the occurrence and the recurrence of DVT or pulmonary embolism (PE) in Japanese patients with acute symptomatic DVT without symptomatic PE.

Study Overview

• Status: Completed
• Conditions: Deep Vein Thrombosis
• Intervention / Treatment: Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Unfractionated heparin; Drug: Warfarin

Detailed Description

The general design of the trial is open label between the Rivaroxaban and the reference arm. However, there are two groups in the Rivaroxaban arm only for the initial 3 weeks. Between these two groups and in this initial period, the study is blinded.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aomori, Japan, 030-8553
  • Fukuoka, Japan, 810-0001
  • Kumamoto, Japan, 862-8505
  • Niigata, Japan, 951-8520
  • Okayama, Japan, 701-1192
  • Osaka, Japan, 530-8480
  • Osaka, Japan, 537-8511
  • Shizuoka, Japan, 424-8636
  • Tokushima, Japan, 770-8503
  • Wakayama, Japan, 640-8158
  • Aichi
    • Toyoake, Aichi, Japan, 470-1192
  • Chiba
    • Sakura, Chiba, Japan, 285-8741
  • Gunma
    • Maebashi, Gunma, Japan, 371-8511
  • Hiroshima
    • Otake, Hiroshima, Japan, 739-0696
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 006-8555
  • Hyogo
    • Takarazuka, Hyogo, Japan, 665-0827
  • Ishikawa
    • Kahoku-gun, Ishikawa, Japan, 920-0293
    • Kanazawa, Ishikawa, Japan, 920-8650
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 245-8575
  • Mie
    • Tsu, Mie, Japan, 514-8507
  • Nagasaki
    • Sasebo, Nagasaki, Japan, 857-8511
  • Osaka
    • Osakasayama, Osaka, Japan, 589-8511
    • Suita, Osaka, Japan, 565-8565
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8655
    • Chuoku, Tokyo, Japan, 104-8560
    • Itabashi-ku, Tokyo, Japan, 173-8610
    • Meguro-ku, Tokyo, Japan, 152-8902
    • Shinagawa, Tokyo, Japan, 141-8625
    • Shinjuku-ku, Tokyo, Japan, 162-8655

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women >/= 20 years of age in patients with confirmed acute symptomatic proximal deep vein thrombosis (DVT) without symptomatic pulmonary embolism (PE)

Exclusion Criteria:

• Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current episode of DVT
• More than 48 hours pre-randomization treatment with therapeutic dosages of anti-coagulant treatment or more than a single dose of warfarin from the onset of the current episode of DVT to randomization
• Calculated creatinine clearance (CLCR) < 30 mL/min
• Subjects with hepatic disease which is associated with coagulopathy leading to a clinically relevant bleeding risk
• Active bleeding or high risk for bleeding contraindicating treatment with unfractioned Heparin (UFH) or warfarin
• Systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm 1	Drug: Rivaroxaban (Xarelto, BAY59-7939); 10 mg twice daily for 21 days, followed by 15 mg once daily; Drug: Rivaroxaban (Xarelto, BAY59-7939); 15 mg twice daily for 21 days, followed by 15 mg once daily
EXPERIMENTAL: Arm 2	Drug: Rivaroxaban (Xarelto, BAY59-7939); 10 mg twice daily for 21 days, followed by 15 mg once daily; Drug: Rivaroxaban (Xarelto, BAY59-7939); 15 mg twice daily for 21 days, followed by 15 mg once daily
ACTIVE_COMPARATOR: Arm 3	Drug: Unfractionated heparin; To be adjusted to maintain the activated partial thromboplastin time (aPTT) prolongation (1.5 to 2.5 times the control)
ACTIVE_COMPARATOR: Arm 4	Drug: Warfarin; To be adjusted on the basis of prothrombin time-international normalized ratio (PT-INR) values target range (1.5 to 2.5)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with newly onset of symptomatic venous thromboembolism (VTE)	Up to 12 months
Number of clinically relevant bleedings	Up to 2 days after last dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with improvement in thrombotic burden	At week 3
Number of participants with deterioration in thrombotic burden	Up to 12 months
Number of participants with the composite of newly onset of symptomatic VTE or asymptomatic deterioration of thrombus	Up to 12 months

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Janssen Scientific Affairs, LLC

Publications and helpful links

General Publications

• Matsuo H, Prins M, Lensing AW, Fujinuma EW, Miyamoto Y, Kajikawa M. Shortened length of hospital stay with rivaroxaban in patients with symptomatic venous thromboembolism in Japan: the J-EINSTEIN pulmonary embolism and deep vein thrombosis program. Curr Med Res Opin. 2015 Jun;31(6):1057-61. doi: 10.1185/03007995.2015.1037728. Epub 2015 May 11.
• Yamada N, Hirayama A, Maeda H, Sakagami S, Shikata H, Prins MH, Lensing AW, Kato M, Onuma J, Miyamoto Y, Iekushi K, Kajikawa M. Oral rivaroxaban for Japanese patients with symptomatic venous thromboembolism - the J-EINSTEIN DVT and PE program. Thromb J. 2015 Jan 17;13:2. doi: 10.1186/s12959-015-0035-3. eCollection 2015. Erratum In: Thromb J. 2016;14:11.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (ACTUAL): December 1, 2013
• Study Completion (ACTUAL): January 1, 2014

Study Registration Dates

• First Submitted: January 20, 2012
• First Submitted That Met QC Criteria: January 20, 2012
• First Posted (ESTIMATE): January 25, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): January 18, 2017
• Last Update Submitted That Met QC Criteria: January 17, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: acute symptomatic deep 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; Heparin; Calcium heparin; Warfarin
• Other Study ID Numbers: 14568