A phase 3, randomized, double-blind, double-dummy, 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 and/or pulmonary embolism.
Secondary IDs if Any
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)
Tablet Edoxaban tosylate(DU-176b) for oral use, 30 mg, one or two tablets daily, maximum of 12 months treatment
low molecular weight heparin and 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
Ages Eligible for Study: 18 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
1) Male or female subjects older than the minimum legal adult age (country specific);
2) Acute symptomatic proximal DVT and/or symptomatic PE confirmed at the site by appropriate diagnostic imaging;
3) Able to provide written informed consent
1) Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current episode of DVT and/or PE;
2) More than 48 hours pre-treatment with anticoagulant therapy prior to randomization;
3) Calculated CrCL < 30 mL/min;
4) 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;
5) patients with active cancer for whom long term treatment with (LMW) heparin is anticipated;
6) active bleeding or high risk for bleeding contraindicating treatment with (LMW) heparin or warfarin;
7) chronic treatment with non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs);
8) treatment with aspirin in a dosage of more than 100 mg/per day or dual antiplatelet therapy;
9) concurrent treatment with potent P-gp inhibitors;
10) 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
Method of Generating Random Sequence
Stratified block randomization
Method of Concealment
Participant, Investigator and Outcome Assessor Blinded
- Symptomatic recurrent VTE, i.e., the composite of DVT, non-fatal PE, and fatal PE
Time Frame: 12 months from time of randomization
- The composite clinical outcome of symptomatic recurrent DVT, non-fatal symptomatic recurrent PE, and all-cause mortality
- Clinically relevant bleeding (i.e., major or clinically relevant non-major bleeding) occurring during treatment
Time Frame: 12 months from time of randomization
Target Sample Size
Total Sample Size="7500" Sample Size from India=""
Phase of Trial
Date of First Enrollment (India)
No Date Specified
Date of First Enrollment (Global)
Estimated Duration of Trial
Years="3" Months="0" Days="0"
Recruitment Status of Trial (Global)
Open to Recruitment
Recruitment Status of Trial (India)
This is a Phase 3, multi-national, multi-center, randomized, double-blind, matching placebo, parallel-group (2 treatment groups), non-inferiority study for efficacy. The maximum treatment period for any individual subject after randomization will be 12 months. While 12 months of treatment are planned, mitigating factors related to the subject?s clinical status will likely influence the total duration of treatment a given subject actually receives. Nevertheless, it is planned that all subjects will be administered a minimum of three months treatment consistent with current American College of Chest Physicians (ACCP) Guidelines. It is anticipated that approximately 10% of subjects will discontinue treatment after 3 months, an additional 40% will discontinue after 6 months, and 50% will complete the entire 12 months of treatment. Treatment durations will be monitored during the study, and the Steering Management Coordinating Committee (SMCC) will take appropriate action to ensure that an approximate proportion of subjects complete the treatment durations as indicated.
Regardless of the total duration of study drug treatment actually received, efficacy and safety data will be collected on all subjects, including those who temporarily interrupt or permanently discontinue study drug, during the entire 12-month period following randomization. For all subjects, contacts (visits or phone calls) are scheduled at regular time points. During these contacts, the treatment and clinical course of the subject will be evaluated. Subjects with suspected efficacy or safety endpoints will undergo confirmatory testing. All subjects, including those who temporarily interrupt or permanently discontinue study drug, will be expected to have the following:
- A Month 12 visit which is critical for the modified intent to treat (mITT) analysis of efficacy,
- A safety follow-up visit approximately 1 month after the last dose of study drug. In this context, last dose means last dose before permanent study drug discontinuation (premature or at the scheduled end of treatment).
Globally approximately 7,500 subjects will be randomized and in India 1000 subjects are targeted to be enrolled.
The date of first patient enrollment in India is May 15, 2010.