Comparative Investigation of Low Molecular Weight (LMW) Heparin/Edoxaban Tosylate (DU176b) Versus (LMW) Heparin/Warfarin in the Treatment of Symptomatic Deep-Vein Blood Clots and/or Lung Blood Clots. (The Edoxaban Hokusai-VTE Study). - Full Text View

Purpose

Evaluation of heparin/edoxaban tosylate (DU176b) versus heparin/warfarin in preventing recurrence of blood clots in patients with acute symptomatic deep-vein blood clots in the legs and/or blood clots in the lungs.

Condition	Intervention	Phase
Venous Thromboembolism Deep Vein Thrombosis (DVT) Pulmonary Embolism (PE) Thromboembolism Venous Thrombosis	Drug: edoxaban tosylate(DU-176b) Drug: low molecular weight heparin/unfractionated heparin Drug: warfarin	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Participant, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase 3, Randomized, Parallel-Group, Multi-Center, Multi-National Study for the Evaluation of Efficacy and Safety of (LMW) Heparin/Edoxaban Versus (LMW) Heparin/Warfarin in Subjects With Symptomatic Deep-Vein Thrombosis (DVT) and or Pulmonary Embolism (PE).

Resource links provided by NLM:

MedlinePlus related topics: Blood Clots Blood Thinners Pulmonary Embolism

Drug Information available for: Warfarin Warfarin sodium Heparin Heparin sodium Edoxaban Edoxaban tosylate

U.S. FDA Resources

Further study details as provided by Daiichi Sankyo Inc.:

Primary Outcome Measures:

Symptomatic Recurrent VTE, i.e., the Composite of DVT, Non-fatal PE, and Fatal PE [ Time Frame: 12 months from time of randomization ]
Symptomatic recurrent Venous Thromboembolism (VTE), i.e., the composite of deep Vein Thrombosis (DVT), non-fatal Pulmonary Embolism (PE), and fatal PE occurring during the Overall Study Period.

Overall Study Period defined as "The time from the reference date (randomization date/initial dose of study drug date) to the last study follow-up visit."

Secondary Outcome Measures:

The Composite Clinical Outcome of Symptomatic Recurrent VTE and All-cause Mortality [ Time Frame: 12 months from time of randomization ]
Clinically Relevant Bleeding (i.e., Major or Clinically Relevant Non-major Bleeding) Occurring During Treatment [ Time Frame: 12 months from time of randomization ]
Clinically relevant bleeding (i.e., major or clinically relevant non-major bleeding) occurring during treatment plus 3 days after their last dose for that time period.


Enrollment:	8292
Study Start Date:	October 2009
Study Completion Date:	April 2013
Primary Completion Date:	April 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: heparin/edoxaban tosylate	Drug: edoxaban tosylate(DU-176b) edoxaban tosylate(DU-176b), film-coated tablet for oral use, 30 mg, two tablets (60 mg) once daily, maximum of 12 months treatment Drug: low molecular weight heparin/unfractionated heparin LMW heparin - subcutaneous injection, 1 mg/Kg twice daily or 1.5 mg/Kg once daily. Unfractionated heparin - 5,000 IU bolus intravenous administration, 1,300 IU/hour continuous infusion, minimum of 5 days and maximum of about 12 days treatment
Active Comparator: heparin/warfarin	Drug: low molecular weight heparin/unfractionated heparin LMW heparin - subcutaneous injection, 1 mg/Kg twice daily or 1.5 mg/Kg once daily. Unfractionated heparin - 5,000 IU bolus intravenous administration, 1,300 IU/hour continuous infusion, minimum of 5 days and maximum of about 12 days treatment Drug: warfarin tablet for oral use; 0.5 mg, 1 mg, 2.5 mg, 5 mg; daily dosage, adjusted to maintain international normalized ratio (INR) between 2.0 and 3.0; maximum of 12 months treatment

Arms

Assigned Interventions

Experimental: heparin/edoxaban tosylate

Drug: edoxaban tosylate(DU-176b)

edoxaban tosylate(DU-176b), film-coated tablet for oral use, 30 mg, two tablets (60 mg) once daily, maximum of 12 months treatment

Drug: low molecular weight heparin/unfractionated heparin

LMW heparin - subcutaneous injection, 1 mg/Kg twice daily or 1.5 mg/Kg once daily.

Unfractionated heparin - 5,000 IU bolus intravenous administration, 1,300 IU/hour continuous infusion, minimum of 5 days and maximum of about 12 days treatment

Active Comparator: heparin/warfarin

Drug: low molecular weight heparin/unfractionated heparin

LMW heparin - subcutaneous injection, 1 mg/Kg twice daily or 1.5 mg/Kg once daily.

Unfractionated heparin - 5,000 IU bolus intravenous administration, 1,300 IU/hour continuous infusion, minimum of 5 days and maximum of about 12 days treatment

Drug: warfarin

tablet for oral use; 0.5 mg, 1 mg, 2.5 mg, 5 mg; daily dosage, adjusted to maintain international normalized ratio (INR) between 2.0 and 3.0; maximum of 12 months treatment

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female subjects older than the minimum legal adult age (country specific);
Acute symptomatic proximal DVT and/or symptomatic PE confirmed at the site by appropriate diagnostic imaging;
Able to provide written informed consent

Exclusion Criteria:

thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current episode of DVT and/or PE;
More than 48 hours pre-treatment with anticoagulant therapy prior to randomization;
Calculated Creatinine clearance (CrCL) < 30 mL/min;
significant liver disease (e.g., acute hepatitis, chronic active hepatitis, cirrhosis) or alanine transaminase (ALT) >\= 2 times the upper limit of normal (ULN), or total bilirubin (TBL) x 1.5 times the ULN;
patients with active cancer for whom long term treatment with (LMW) heparin is anticipated;
active bleeding or high risk for bleeding contraindicating treatment with (LMW) heparin or warfarin;
chronic treatment with non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs);
treatment with aspirin in a dosage of more than 100 mg/per day or dual antiplatelet therapy;
concurrent treatment with potent P-gp inhibitors;
subjects with any condition that, as judged by the investigator, would place the subject at increased risk of harm if he/she participated in the study

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00986154

Show 454 Study Locations

Sponsors and Collaborators

Daiichi Sankyo Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Brekelmans MP, Ageno W, Beenen LF, Brenner B, Buller HR, Chen CZ, Cohen AT, Grosso MA, Meyer G, Raskob G, Segers A, Vanassche T, Verhamme P, Wells PS, Zhang G, Weitz JI. Recurrent venous thromboembolism in patients with pulmonary embolism and right ventricular dysfunction: a post-hoc analysis of the Hokusai-VTE study. Lancet Haematol. 2016 Sep;3(9):e437-45. doi: 10.1016/S2352-3026(16)30080-1.

Raskob GE, van Es N, Segers A, Angchaisuksiri P, Oh D, Boda Z, Lyons RM, Meijer K, Gudz I, Weitz JI, Zhang G, Lanz H, Mercuri MF, Büller HR; Hokusai-VTE investigators. Edoxaban for venous thromboembolism in patients with cancer: results from a non-inferiority subgroup analysis of the Hokusai-VTE randomised, double-blind, double-dummy trial. Lancet Haematol. 2016 Aug;3(8):e379-87. doi: 10.1016/S2352-3026(16)30057-6. Epub 2016 Jul 1.

Nakamura M, Wang YQ, Wang C, Oh D, Yin WH, Kimura T, Miyazaki K, Abe K, Mercuri M, Lee LH, Segers A, Büller H. Efficacy and safety of edoxaban for treatment of venous thromboembolism: a subanalysis of East Asian patients in the Hokusai-VTE trial. J Thromb Haemost. 2015 Sep;13(9):1606-14. doi: 10.1111/jth.13055. Epub 2015 Aug 27.

Hokusai-VTE Investigators, Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013 Oct 10;369(15):1406-15. doi: 10.1056/NEJMoa1306638. Epub 2013 Aug 31. Erratum in: N Engl J Med. 2014 Jan 23;370(4):390.

Camm AJ, Bounameaux H. Edoxaban: a new oral direct factor xa inhibitor. Drugs. 2011 Aug 20;71(12):1503-26. doi: 10.2165/11595540-000000000-00000.


Responsible Party:	Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:	NCT00986154 History of Changes
Other Study ID Numbers:	DU176b-D-U305 The Edoxaban Hokusai VTE Study
Study First Received:	September 25, 2009
Results First Received:	February 5, 2015
Last Updated:	March 13, 2015

Keywords provided by Daiichi Sankyo Inc.:


Recurrent Thrombosis Recurrent Pulmonary Embolism Symptomatic Deep Vein Thrombosis Symptomatic Pulmonary Embolism Venous Thromboembolism (VTE)

Additional relevant MeSH terms:


Thrombosis Thromboembolism Embolism Venous Thromboembolism Pulmonary Embolism Venous Thrombosis Embolism and Thrombosis Vascular Diseases Cardiovascular Diseases Lung Diseases Respiratory Tract Diseases Calcium heparin Edoxaban	Heparin Warfarin Heparin, Low-Molecular-Weight Dalteparin Anticoagulants Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action Factor Xa Inhibitors Antithrombins Serine Proteinase Inhibitors Protease Inhibitors Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 13, 2017