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

NCT ID: NCT01662908

Last Updated: 2019-02-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 85 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2014-03-31

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.

Detailed Description

The classical management of patients with venous thromboembolism (VTE) consists of an initial treatment of at least five days of a (LMW) heparin followed by long-term treatment with a vitamin K antagonist (VKA), such as warfarin. The eTRIS study will address the clinically important question of whether edoxaban monotherapy, without concomitant (LMW) heparin at the time of treatment initiation is comparable to or better than standard treatment with (LMW) heparin/warfarin therapy in subjects with acute symptomatic DVT as assessed by the relative change from baseline in thrombus volume (measured by MRI) at Day 14-21.

Conditions

Deep Vein Thrombosis; Venous Thrombosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

edoxaban tosylate

Group Type: EXPERIMENTAL

edoxaban tosylate

Intervention Type: 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

heparin/warfarin

Group Type: ACTIVE_COMPARATOR

enoxaparin/unfractionated heparin

Intervention Type: 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.

warfarin

Intervention Type: DRUG

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

Interventions

edoxaban tosylate

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

Intervention Type: DRUG

enoxaparin/unfractionated heparin

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.

Intervention Type: DRUG

warfarin

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Treatment with P-gp inhibitors is not permitted at the time of randomization; subsequent use is permitted, with a dose reduction in the edoxaban monotherapy treatment arm.
• Known history of positive Hepatitis B antigen or Hepatitis C antibody
• Subjects with any condition that, as judged by the investigator, would put the subject at increased risk of harm if he/she participated in the study; including, but not limited to, subjects at increased risk of harm if given a gadolinium-based contrast agent such as gadofosveset trisodium (Ablavar®)
• Subjects for whom MRI would be contraindicated (e.g., subjects with metal implants) or for whom the use of a gadolinium-based contrast agent such as gadofosveset trisodium (Ablavar®) would be contraindicated
• Subject has previously entered this study or another edoxaban study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Samuel Z Goldhaber, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Dothan, Alabama, United States

Montgomery, Alabama, United States

Sacramento, California, United States

Atlantis, Florida, United States

Clearwater, Florida, United States

Fort Myers, Florida, United States

Jacksonville, Florida, United States

Sarasota, Florida, United States

Tampa, Florida, United States

Jonesboro, Georgia, United States

Lafayette, Indiana, United States

Paducah, Kentucky, United States

Covington, Louisiana, United States

Annapolis, Maryland, United States

Baltimore, Maryland, United States

Randallstown, Maryland, United States

Butte, Montana, United States

Grand Island, Nebraska, United States

Rochester, New York, United States

Durham, North Carolina, United States

Greensboro, North Carolina, United States

Wilmington, North Carolina, United States

Maumee, Ohio, United States

Camp Hill, Pennsylvania, United States

Ephrata, Pennsylvania, United States

Sellersville, Pennsylvania, United States

Rapid City, South Dakota, United States

Fredericksburg, Virginia, United States

Tacoma, Washington, United States

Edmonton, Alberta, Canada

London, Ontario, Canada

Newmarket, Ontario, Canada

Greenfield Park, Quebec, Canada

Montreal, Quebec, Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 27165711 (View on PubMed)

Other Identifiers

DU176b-D-U211

Identifier Type: -

Identifier Source: org_study_id