title: The design and rationale for the Acute Medically Ill Venous Thromboembolism Prevention with Extended Duration Betrixaban (APEX) study.
abstract: Randomized clinical trials have identified a population of acute medically ill patients who remain at risk for venous thromboembolism (VTE) beyond the standard duration of therapy and hospital discharge. The aim of the APEX study is to determine whether extended administration of oral betrixaban (35-42 days) is superior to a standard short course of prophylaxis with subcutaneous enoxaparin (10 ± 4 days followed by placebo) in patients with known risk factors for post-discharge VTE. Patients initially are randomized to receive either betrixaban or enoxaparin (and matching placebo) in a double dummy design. Following a standard duration period of enoxaparin treatment (with placebo tablets) or betrixaban (with placebo injections), patients receive only betrixaban (or alternative matching placebo). Patients are considered for enrollment if they are older than 40 years, have a specified medical illness, and restricted mobility. They must also meet the APEX criteria for increased VTE risk (aged ≥75 years, baseline D-Dimer ≥2× upper the limit of "normal", or 2 additional ancillary risk factors for VTE). The primary efficacy end point is the composite of asymptomatic proximal deep venous thrombosis, symptomatic deep venous thrombosis, non-fatal (pulmonary embolus) pulmonary embolism, or VTE-related death through day 35. The primary safety outcome is the occurrence of major bleeding. We hypothesize that extended duration betrixaban VTE prophylaxis will be safe and more effective than standard short duration enoxaparin in preventing VTE in acute medically ill patients with known risk factors for post hospital discharge VTE.
authors.affiliation: Department of Haematological Medicine, King's College Hospital, London, United Kingdom. Electronic address: Alexander.cohen@kcl.ac.uk.
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Cohen
authors.affiliation: Department of Medicine, Stanford University, School of Medicine, Stanford, CA.
authors.forename: Robert
authors.initials: R
authors.lastname: Harrington
authors.affiliation: Harvard Medical School, Boston, MA.
authors.forename: Samuel Z
authors.initials: SZ
authors.lastname: Goldhaber
authors.affiliation: University of Calgary, Alberta, Canada.
authors.forename: Russell
authors.initials: R
authors.lastname: Hull
authors.affiliation: Harvard Medical School, Boston, MA.
authors.forename: C Michael
authors.initials: CM
authors.lastname: Gibson
authors.affiliation: Duke Clinical Research Institute, Durham, NC.
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Hernandez
authors.affiliation: Afferent Pharmaceuticals, Inc, San Mateo, CA; Formerly of Portola Pharmaceuticals, Inc., South San Francisco, CA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Kitt
authors.affiliation: Portola Pharmaceuticals, Inc, South San Francisco, CA.
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Lorenz
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage*; D001549:Benzamides / Q000008:administration & dosage*; D004311:Double-Blind Method; D017984:Enoxaparin / Q000008:administration & dosage*; D065427:Factor Xa Inhibitors; D006801:Humans; D038622:Internationality; D008875:Middle Aged; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage*; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D001549:Benzamides; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D011725:Pyridines; C543086:betrixaban