A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT)

Alexander G G Turpie, Kenneth A. Bauer, Bruce L. Davidson, William D. Fisher, Michael Gent, Michael H. Huo, Uma Sinha, Daniel D. Gretler

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

Betrixaban is an oral direct inhibitor of factor Xa (FXa) being developed for the prevention of venous thromboembolism (VTE). Its antithrombotic effects had not been previously tested in patients. This exploratory clinical trial in the US and Canada randomized 215 patients undergoing elective total knee replacement (TKR) in a 2:2:1 ratio to receive post-operative betrixaban 15 mg or 40 mg p.o. bid or enoxaparin 30 mg s.c. q 12h, respectively, for 10-14 days.The betrixaban dosage was blinded, but enoxaparin was not. Primary efficacy outcome was the incidence ofVTE, consisting of deep-vein thrombosis (DVT) on mandatory unilateral (operated leg) venography, symptomatic proximal DVT, or pulmonary embolism (PE) through Day 10-14. Safety outcomes included major and clinically significant non-major bleeds through 48 h after treatment. All efficacy and bleeding outcomes were adjudicated by a blinded independent central adjudication committee. Of 214 treated patients, 175 (82%) were evaluable for primary efficacy. VTE incidence was 14/70 (20%; 95% CI: 11, 31) for betrixaban 15 mg, 10/65 (15%; 95% CI: 8, 27) for betrixaban 40 mg, and 4/40 (10%; 95% CI: 3, 24) for enoxaparin. No bleeds were reported for betrixaban 15 mg, 2 (2.4%) clinically significant non-major bleeds with betrixaban 40 mg, and one (2.3%) major and two (4.6%) clinically significant non-major bleeds with enoxaparin. A dose- and concentration-dependent effect of betrixaban on inhibition of thrombin generation and anti-Xa levels was observed. Betrixaban demonstrated antithrombotic activity and appeared well tolerated in knee replacement patients at the doses studied.

Original languageEnglish (US)
Pages (from-to)68-76
Number of pages9
JournalThrombosis and Haemostasis
Volume101
Issue number1
DOIs
StatePublished - Jan 2009

Fingerprint

Knee Replacement Arthroplasties
Enoxaparin
Venous Thromboembolism
Venous Thrombosis
Factor Xa Inhibitors
betrixaban
Phlebography
Incidence
Pulmonary Embolism
Thrombin
Canada
Leg
Knee
Clinical Trials
Hemorrhage
Safety

Keywords

  • Betrixaban
  • Clinical trials
  • Direct factor Xa inhibitor
  • Major bleed
  • Oral anticoagulants
  • Total knee replacement (TKR)
  • Venous thrombosis

ASJC Scopus subject areas

  • Hematology

Cite this

A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT). / Turpie, Alexander G G; Bauer, Kenneth A.; Davidson, Bruce L.; Fisher, William D.; Gent, Michael; Huo, Michael H.; Sinha, Uma; Gretler, Daniel D.

In: Thrombosis and Haemostasis, Vol. 101, No. 1, 01.2009, p. 68-76.

Research output: Contribution to journalArticle

Turpie, Alexander G G ; Bauer, Kenneth A. ; Davidson, Bruce L. ; Fisher, William D. ; Gent, Michael ; Huo, Michael H. ; Sinha, Uma ; Gretler, Daniel D. / A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT). In: Thrombosis and Haemostasis. 2009 ; Vol. 101, No. 1. pp. 68-76.
@article{741233861a544033b6537fcce741809f,
title = "A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT)",
abstract = "Betrixaban is an oral direct inhibitor of factor Xa (FXa) being developed for the prevention of venous thromboembolism (VTE). Its antithrombotic effects had not been previously tested in patients. This exploratory clinical trial in the US and Canada randomized 215 patients undergoing elective total knee replacement (TKR) in a 2:2:1 ratio to receive post-operative betrixaban 15 mg or 40 mg p.o. bid or enoxaparin 30 mg s.c. q 12h, respectively, for 10-14 days.The betrixaban dosage was blinded, but enoxaparin was not. Primary efficacy outcome was the incidence ofVTE, consisting of deep-vein thrombosis (DVT) on mandatory unilateral (operated leg) venography, symptomatic proximal DVT, or pulmonary embolism (PE) through Day 10-14. Safety outcomes included major and clinically significant non-major bleeds through 48 h after treatment. All efficacy and bleeding outcomes were adjudicated by a blinded independent central adjudication committee. Of 214 treated patients, 175 (82{\%}) were evaluable for primary efficacy. VTE incidence was 14/70 (20{\%}; 95{\%} CI: 11, 31) for betrixaban 15 mg, 10/65 (15{\%}; 95{\%} CI: 8, 27) for betrixaban 40 mg, and 4/40 (10{\%}; 95{\%} CI: 3, 24) for enoxaparin. No bleeds were reported for betrixaban 15 mg, 2 (2.4{\%}) clinically significant non-major bleeds with betrixaban 40 mg, and one (2.3{\%}) major and two (4.6{\%}) clinically significant non-major bleeds with enoxaparin. A dose- and concentration-dependent effect of betrixaban on inhibition of thrombin generation and anti-Xa levels was observed. Betrixaban demonstrated antithrombotic activity and appeared well tolerated in knee replacement patients at the doses studied.",
keywords = "Betrixaban, Clinical trials, Direct factor Xa inhibitor, Major bleed, Oral anticoagulants, Total knee replacement (TKR), Venous thrombosis",
author = "Turpie, {Alexander G G} and Bauer, {Kenneth A.} and Davidson, {Bruce L.} and Fisher, {William D.} and Michael Gent and Huo, {Michael H.} and Uma Sinha and Gretler, {Daniel D.}",
year = "2009",
month = "1",
doi = "10.1160/TH08-07-0460",
language = "English (US)",
volume = "101",
pages = "68--76",
journal = "Thrombosis and Haemostasis",
issn = "0340-6245",
publisher = "Schattauer GmbH",
number = "1",

}

TY - JOUR

T1 - A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT)

AU - Turpie, Alexander G G

AU - Bauer, Kenneth A.

AU - Davidson, Bruce L.

AU - Fisher, William D.

AU - Gent, Michael

AU - Huo, Michael H.

AU - Sinha, Uma

AU - Gretler, Daniel D.

PY - 2009/1

Y1 - 2009/1

N2 - Betrixaban is an oral direct inhibitor of factor Xa (FXa) being developed for the prevention of venous thromboembolism (VTE). Its antithrombotic effects had not been previously tested in patients. This exploratory clinical trial in the US and Canada randomized 215 patients undergoing elective total knee replacement (TKR) in a 2:2:1 ratio to receive post-operative betrixaban 15 mg or 40 mg p.o. bid or enoxaparin 30 mg s.c. q 12h, respectively, for 10-14 days.The betrixaban dosage was blinded, but enoxaparin was not. Primary efficacy outcome was the incidence ofVTE, consisting of deep-vein thrombosis (DVT) on mandatory unilateral (operated leg) venography, symptomatic proximal DVT, or pulmonary embolism (PE) through Day 10-14. Safety outcomes included major and clinically significant non-major bleeds through 48 h after treatment. All efficacy and bleeding outcomes were adjudicated by a blinded independent central adjudication committee. Of 214 treated patients, 175 (82%) were evaluable for primary efficacy. VTE incidence was 14/70 (20%; 95% CI: 11, 31) for betrixaban 15 mg, 10/65 (15%; 95% CI: 8, 27) for betrixaban 40 mg, and 4/40 (10%; 95% CI: 3, 24) for enoxaparin. No bleeds were reported for betrixaban 15 mg, 2 (2.4%) clinically significant non-major bleeds with betrixaban 40 mg, and one (2.3%) major and two (4.6%) clinically significant non-major bleeds with enoxaparin. A dose- and concentration-dependent effect of betrixaban on inhibition of thrombin generation and anti-Xa levels was observed. Betrixaban demonstrated antithrombotic activity and appeared well tolerated in knee replacement patients at the doses studied.

AB - Betrixaban is an oral direct inhibitor of factor Xa (FXa) being developed for the prevention of venous thromboembolism (VTE). Its antithrombotic effects had not been previously tested in patients. This exploratory clinical trial in the US and Canada randomized 215 patients undergoing elective total knee replacement (TKR) in a 2:2:1 ratio to receive post-operative betrixaban 15 mg or 40 mg p.o. bid or enoxaparin 30 mg s.c. q 12h, respectively, for 10-14 days.The betrixaban dosage was blinded, but enoxaparin was not. Primary efficacy outcome was the incidence ofVTE, consisting of deep-vein thrombosis (DVT) on mandatory unilateral (operated leg) venography, symptomatic proximal DVT, or pulmonary embolism (PE) through Day 10-14. Safety outcomes included major and clinically significant non-major bleeds through 48 h after treatment. All efficacy and bleeding outcomes were adjudicated by a blinded independent central adjudication committee. Of 214 treated patients, 175 (82%) were evaluable for primary efficacy. VTE incidence was 14/70 (20%; 95% CI: 11, 31) for betrixaban 15 mg, 10/65 (15%; 95% CI: 8, 27) for betrixaban 40 mg, and 4/40 (10%; 95% CI: 3, 24) for enoxaparin. No bleeds were reported for betrixaban 15 mg, 2 (2.4%) clinically significant non-major bleeds with betrixaban 40 mg, and one (2.3%) major and two (4.6%) clinically significant non-major bleeds with enoxaparin. A dose- and concentration-dependent effect of betrixaban on inhibition of thrombin generation and anti-Xa levels was observed. Betrixaban demonstrated antithrombotic activity and appeared well tolerated in knee replacement patients at the doses studied.

KW - Betrixaban

KW - Clinical trials

KW - Direct factor Xa inhibitor

KW - Major bleed

KW - Oral anticoagulants

KW - Total knee replacement (TKR)

KW - Venous thrombosis

UR - http://www.scopus.com/inward/record.url?scp=60849097858&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=60849097858&partnerID=8YFLogxK

U2 - 10.1160/TH08-07-0460

DO - 10.1160/TH08-07-0460

M3 - Article

VL - 101

SP - 68

EP - 76

JO - Thrombosis and Haemostasis

JF - Thrombosis and Haemostasis

SN - 0340-6245

IS - 1

ER -