Table 2.

Design of Phase II and Phase III clinical trials of betrixaban

Study (ref)	Indication	Sample size	Intervention arms	Control arms	Design	Clinical outcomes
Phase II (EXPERT13)	VTE prevention total knee replacement	214	Betrixaban 15 mg bid and 40 mg bid orally, 6 h postoperatively	Enoxaparin 30 mg sc bid, 12–24 h postoperatively	RCT, open label but blinded to betrixaban doses	Primary efficacy: composite of proximal and distal DVT identified by unilateral mandatory venography of operated leg + symptomatic proximal DVT or PE between day 10 and day 14 Primary safety: composite of major and clinically significant nonmajor bleeding.
Phase II (EXPLORE-Xa12)	Stroke prevention in atrial fibrillation	561	Betrixaban 40 mg, 60 mg, and 80 mg daily	Warfarin adjusted to INR 2.0–3.0	RCT, open label, but blinded to betrixaban doses	Primary safety: composite of major or clinically relevant nonmajor bleeding. Secondary efficacy: composite of death, ischemic or nonischemic stroke, MI, or systemic embolism.
Phase III (APEX14)	Extended prophylaxis in high VTE risk acutely ill medical patients	6,850 (planned)	Betrixaban 80 mg daily for 35–42 days	Enoxaparin 40 mg up to 10±4 days followed by placebo	RCT, blinded, double dummy	Primary efficacy: composite of proximal DVT-(detected by mandatory ultrasound), symptomatic DVT-, nonfatal PE- and VTE-related death between days 35 and 42. Primary safety: major bleeding through 7 days after discontinuation of all study medications.

Abbreviations: VTE, venous thromboembolism; h, hours; INR, international normalized ratio; RCT, randomized controlled trial; DVT, deep vein thrombosis; PE, pulmonary embolism; MI, myocardial infarction.