Clinical trial NCT01662908: 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
Official title: A Randomized, Open-Label, Parallel-Group, Multi-Center Study for the Evaluation of Efficacy and Safety of Edoxaban Monotherapy Versus (LMW) Heparin/Warfarin in Subjects With Symptomatic Deep-Vein Thrombosis - Edoxaban Thrombus Reduction Imaging Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Deep Vein Thrombosis
Venous Thrombosis
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2012-08-13
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Relative Change From Baseline in Thrombus Volume Assessed by MRI [Using the Magnetic Resonance Venography (MRV) Method]
timeFrame: Baseline to final visit (Day 14-21)
Secondary outcomes:
measure: Number of Participants With Clinically Relevant Bleeding
timeFrame: Initial dose of study drug up to 3 days after last dose
measure: Number of Participants With Recurrence of Venous Thromboembolism (VTE)
timeFrame: Baseline to final visit (Day 14-21)
measure: Number of Participants With Major Adverse Cardiovascular Events (MACE)
timeFrame: Initial dose of study drug up to 3 days after last dose
measure: Number of Participants With Change From Baseline in the Presence or Absence of Thrombus by Vessel
timeFrame: Baseline to final visit (Day 14-21)
Other outcomes:
Locations:
city: Dothan
country: United States
state: Alabama
city: Montgomery
country: United States
state: Alabama
city: Sacramento
country: United States
state: California
city: Atlantis
country: United States
state: Florida
city: Clearwater
country: United States
state: Florida
city: Fort Myers
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Jonesboro
country: United States
state: Georgia
city: Lafayette
country: United States
state: Indiana
city: Paducah
country: United States
state: Kentucky
city: Covington
country: United States
state: Louisiana
city: Annapolis
country: United States
state: Maryland
city: Baltimore
country: United States
state: Maryland
city: Randallstown
country: United States
state: Maryland
city: Butte
country: United States
state: Montana
city: Grand Island
country: United States
state: Nebraska
city: Rochester
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Greensboro
country: United States
state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: Maumee
country: United States
state: Ohio
city: Camp Hill
country: United States
state: Pennsylvania
city: Ephrata
country: United States
state: Pennsylvania
city: Sellersville
country: United States
state: Pennsylvania
city: Rapid City
country: United States
state: South Dakota
city: Fredericksburg
country: United States
state: Virginia
city: Tacoma
country: United States
state: Washington
city: Edmonton
country: Canada
state: Alberta
city: London
country: Canada
state: Ontario
city: New Market
country: Canada
state: Ontario
city: Greenfield Park
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
Study officials:
affiliation: Brigham and Women's Hospital
name: Samuel Z Goldhaber, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.