A Randomized, Open-Label, Parallel-Group, Multi-Center Study for the Evaluation of Efficacy and Safety of Edoxaban Monotherapy Versus Low Molecular Weight (LMW) Heparin/Warfarin in Subjects With Symptomatic Deep-Vein Thrombosis

NCT01662908 | Completed Phase 2 Results

• 1 other identifier: DU176b-D-U211
• Study Type: interventional
• Target: 85
• Locations: 2 countries
• Sites: 34

Brief Summary

Assess the relative change in thrombus volume as determined by two assessments (Baseline and Day 14-21) with magnetic resonance venography (MRV) in subjects with deep-vein thrombosis (DVT) treated with either an edoxaban monotherapy regimen or a low molecular weight (LMW) heparin/warfarin regimen.

Conditions

Deep Vein Thrombosis; Venous Thrombosis

Outcome Measures

Primary Outcomes (1)

• Relative Change From Baseline in Thrombus Volume Assessed by MRI [Using the Magnetic Resonance Venography (MRV) Method]

  Thrombus Volume (mm\^3) was measured at baseline and between days 14 to 21 using MRI results as determined by Magnetic Resonance Venography (MRV) method, and the relative percentage change from baseline was calculated

  Baseline to final visit (Day 14-21)

Secondary Outcomes (4)

• Number of Participants With Clinically Relevant Bleeding

  Initial dose of study drug up to 3 days after last dose

• Number of Participants With Recurrence of Venous Thromboembolism (VTE)

  Baseline to final visit (Day 14-21)

• Number of Participants With Major Adverse Cardiovascular Events (MACE)

  Initial dose of study drug up to 3 days after last dose

• Number of Participants With Change From Baseline in the Presence or Absence of Thrombus by Vessel

  Baseline to final visit (Day 14-21)

Study Arms (2)

edoxaban tosylate

EXPERIMENTAL

Drug: edoxaban tosylate

heparin/warfarin

ACTIVE COMPARATOR

Drug: enoxaparin/unfractionated heparin; Drug: warfarin

Interventions

edoxaban tosylate DRUG

edoxaban tosylate (DU-176b), film-coated for oral use, 90 mg once daily (QD) for 10 days (±2 days) followed by 60 mg QD for a total of approximately 90 days of edoxaban treatment

edoxaban tosylate

enoxaparin/unfractionated heparin DRUG

enoxaparin - administered by subcutaneous injection;1 mg/kg/ twice daily or 1.5 mg/kg once daily unfractionated heparin - started with 5000 IU bolus intravenous administration, 1300 IU/h continuous infusion, minimum of 5 days of treatment and stopped when target INR (2.0 - 3.0) is achieved.

heparin/warfarin

warfarin DRUG

tablet for oral use; daily dosage, adjusted to maintain international normalized ratio (INR) between 2.0 and 3.0; 90 days treatment.

heparin/warfarin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects older than the minimum legal adult age (country specific)
• Acute symptomatic proximal DVT involving the popliteal, femoral or iliac veins confirmed by compression ultrasonography (CUS) or other appropriate imaging techniques (such as venography or spiral/contrast CT) with symptom onset \< or = 1week prior to randomization
• Able to provide signed informed consent

You may not qualify if:

• Concomitant pulmonary embolism known to the investigator at the time of randomization
• Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current episode of DVT
• Indication for warfarin other than DVT
• More than 48 hours pre-treatment with therapeutic dosages of anti-coagulant treatment \[low molecular weight heparin (LMWH), unfractionated heparin (UFH), fondaparinux, VKA, factor Xa inhibitor or other anti coagulant per local labeling\] prior to randomization to treat the current episode
• Treatment with any investigational drug within 30 days prior to randomization
• Calculated creatinine clearance (CrCL) \< 30 mL/min
• Significant liver disease (e.g., acute hepatitis, chronic active hepatitis, cirrhosis) or alanine aminotransferase (ALT) \> or = 2 times the upper limit of normal (ULN), or total bilirubin (TBL) \> or = to 1.5 times the ULN (however subjects whose elevated TBL is due to known Gilbert's syndrome may be included in the study)
• Subjects with active cancer for whom long term treatment with (LMW) heparin is anticipated
• Life expectancy \< 3 months
• Active bleeding or high risk for bleeding contraindicating treatment with (LMW) heparin or warfarin
• Uncontrolled hypertension as judged by the Investigator (e.g., systolic blood pressure \> 170 mmHg or diastolic blood pressure \> 100 mmHg despite antihypertensive medications confirmed by repeat measurement)
• Women of childbearing potential without proper contraceptive measures (i.e., a method of contraception with a failure rate \< 1 % during the course of the study including the observational period) and women who are pregnant or breast feeding
• Any contraindication listed in the local labeling of LMWH, UFH, or warfarin
• Chronic treatment with non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) including both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX- 2) inhibitors for \> or = 4 days/week anticipated to continue during the study.
• Treatment with aspirin in a dosage of more than 100 mg/per day or dual antiplatelet therapy (any two antiplatelet agents including aspirin plus any other oral or intravenous \[IV\] antiplatelet drug) anticipated to continue during the study

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (34)

Unknown Facility

Dothan, Alabama, United States

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Montgomery, Alabama, United States

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Sacramento, California, United States

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Atlantis, Florida, United States

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Clearwater, Florida, United States

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Fort Myers, Florida, United States

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Jacksonville, Florida, United States

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Sarasota, Florida, United States

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Tampa, Florida, United States

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Jonesboro, Georgia, United States

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Lafayette, Indiana, United States

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Paducah, Kentucky, United States

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Covington, Louisiana, United States

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Annapolis, Maryland, United States

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Baltimore, Maryland, United States

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Randallstown, Maryland, United States

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Butte, Montana, United States

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Grand Island, Nebraska, United States

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Rochester, New York, United States

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Durham, North Carolina, United States

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Greensboro, North Carolina, United States

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Wilmington, North Carolina, United States

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Maumee, Ohio, United States

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Camp Hill, Pennsylvania, United States

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Ephrata, Pennsylvania, United States

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Sellersville, Pennsylvania, United States

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Rapid City, South Dakota, United States

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Fredericksburg, Virginia, United States

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Tacoma, Washington, United States

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Edmonton, Alberta, Canada

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London, Ontario, Canada

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Newmarket, Ontario, Canada

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Greenfield Park, Quebec, Canada

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Montreal, Quebec, Canada

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Related Publications (1)

• Piazza G, Mani V, Goldhaber SZ, Grosso MA, Mercuri M, Lanz HJ, Schussler S, Hsu C, Chinigo A, Ritchie B, Nadar V, Cannon K, Pullman J, Concha M, Schul M, Fayad ZA; edoxaban Thrombus Reduction Imaging Study (eTRIS) Investigators. Magnetic resonance venography to assess thrombus resolution with edoxaban monotherapy versus parenteral anticoagulation/warfarin for symptomatic deep vein thrombosis: A multicenter feasibility study. Vasc Med. 2016 Aug;21(4):361-8. doi: 10.1177/1358863X16645853. Epub 2016 May 10.

  PMID: 27165711 DERIVED

MeSH Terms

Conditions

Venous Thrombosis

Interventions

edoxaban; Enoxaparin; Heparin; Warfarin

Condition Hierarchy (Ancestors)

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Glycosaminoglycans; Polysaccharides; Carbohydrates; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Senior Director, CVM TA Development
• Organization: Daiichi Sankyo, Inc.

732-590-5000

Study Officials

• Samuel Z Goldhaber, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2012
• First Posted: August 13, 2012
• Study Start: August 1, 2012
• Primary Completion: January 1, 2014
• Study Completion: March 1, 2014
• Last Updated: February 26, 2019
• Results First Posted: May 12, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

US (29); CA (5)