In This SectionTexas Health Research & Education Institute
Disease or Condition
Evaluation of efficacy and safety of (LMW) heparin/edoxaban versus (LMW) heparin/warfarin in subjects with symptomatic deep-vein thrombosis and/or pulmonary embolism (Pulmonary)
To evaluate whether initial (Low Molecular Weight) heparin followed by edoxaban only ([LMW] heparin/edoxaban) is non-inferior to initial (LMW) heparin overlapping with warfarin, followed by warfarin only ([LMW] heparin/warfarin) in the treatment of subjects with acute symptomatic VTE for the prevention of symptomatic recurrent VTE during the 12-month study period.
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.
Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current episode of DVT and/or PE.
Indication for warfarin other than DVT and/or PE.
More than 48 hours pre-treatment with therapeutic dosages of anticoagulant treatment (LMWH, UFH, and fondaparinux per local labeling) or more than a single dose of a VKA prior to randomization to treat the current episode.
Treatment with any investigational drug within 30 days prior to randomization.
Calculated 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) ³ 1.5 times the ULN.
Patients 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 antihypertensives).
Women of childbearing potential without proper contraceptive measures, and women who are pregnant or breast feeding:
Note: 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). These methods of contraception according to the note for guidance on non-clinical safety studies for the conduct of human trials for pharmaceuticals (CPMP/ICH/286/95, modification) include consistent and correct use of hormone containing implants and injectables, combined oral contraceptives, hormone containing intrauterine devices, surgical sterilization, sexual abstinence, and vasectomy for the male partner).
Any other 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 ³ 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 invravenous (IV) antiplatelet drug) anticipated to continue during the study.
Treatment with the potent P-gp inhibitors ritonavir, nelfinavir, indinavir, or saquinavir anticipated to continue during the study.
Systemic use of the anti-arrythmic drug dronedarone at the time of randomization (subjects randomized to study prior to Amendment 2 will have their edoxaban dose reduced).
Systemic use of the strong P-gp inhibitors erythromycin, azithromycin, larithromycin, ketoconazole or itraconazole at the time of randomization; subsequent use is permitted.
Known history of positive Hepatitis B antigen or Hepatitis C antibody.
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.