News | March 19, 2010

Factor Xa Inhibitor Reduced Bleeding Compared to Warfarin in AF Patients

March 19, 2010 – An experimental factor Xa inhibitor given to patients with non-valvular atrial fibrillation (AF) or atrial flutter and at least one risk factor for stroke, reduced the incidence of major and clinically relevant non-major (CRNM) bleeds compared to dose-adjusted warfarin.

The data were presented during a late-breaking clinical trials session this week at the American College of Cardiology (ACC) 59th Annual Scientific Session in Atlanta. The results were from EXPLORE-Xa, a phase two exploratory dose finding study of betrixaban, an investigational oral direct factor Xa inhibitor.

"Given that bleeding can be a significant safety issue for patients who take warfarin, there is a critical unmet need for anticoagulant therapy options," said U.S. national coordinator in the study, Michael Ezekowitz, MB, ChB, DPhil, vice president of the Lankenau Institute for Medical Research and professor at Jefferson Medical College. "The EXPLORE-Xa study accomplished its objective of providing important information to guide the betrixaban dosing strategy for future investigational studies."

In this multinational, dose-finding study of 508 patients with non-valvular AF or atrial flutter and at least one risk factor for stroke, a once daily dose of betrixaban 40 mg (n=127) demonstrated significantly less major and CRNM bleeding than open label warfarin (n=127). The risk of major and CRNM bleeding for the 60 mg (n=127) and 80 mg (n=127) doses of betrixaban was similar to warfarin.

About the EXPLORE-Xa Study

The phase 2b randomized, parallel group study examined three blinded doses of betrixaban compared with open-label, dose-adjusted warfarin in 508 patients. Patients ranged from ages 46 to 91 and a total of 87 percent previously received a vitamin K antagonist. Participants were not excluded for severe renal impairment, except those on dialysis. One hundred and twenty-seven patients were randomized to each of four treatment groups: betrixaban 40, 60 or 80 mg or open-label warfarin (INR 2-3), the current standard of care. The study was conducted in 35 centers in the U.S., Canada and Germany with a minimum follow-up of three months and a maximum of 12 months. The goal of the study was to assess the safety and tolerability of betrixaban compared to warfarin to provide information to guide further clinical development.

The primary study endpoint was the time to occurrence of major or CRNM bleeding. The incidence (crude rates) of major or CRNM bleeding was 0.8 percent, 3.9 percent, 3.9 percent and 5.5 percent for the betrixaban 40 mg, 60 mg, and 80 mg and warfarin groups, respectively.

The secondary endpoints included the time to occurrence of any bleeding (major, CRNM, and minimal) and the time to occurrence of death, stroke (ischemic or hemorrhagic), myocardial infarction, or other systemic embolism. The incidence (crude rates) of any bleeding was significantly lower compared to warfarin (31.5 percent) for patients taking betrixaban 40 mg (17.3 percent) and 80 mg (18.9 percent); but not those taking betrixaban 60 mg (25.2 percent). The number of events in the secondary composite endpoint of death, stroke, myocardial infarction or other systemic embolism ranged from zero to one in each of the four dosing groups, which was the expected stroke/embolic event rate for the warfarin control group. There was one stroke each in the betrixaban 60 mg and 80 mg groups, and one death each in the betrixaban 40 mg and warfarin groups. There were no myocardial infarctions or other systemic emboli in any of the four dosing groups.

The most common adverse events in the betrixaban groups combined (n=381) were diarrhea (6 percent versus 0.8 percent on warfarin); nausea (5.5 vs. 1.6 percent on warfarin); constipation (5.2 vs. 2.4 percent on warfarin); headache (5.2 vs. 2.4 percent on warfarin) and peripheral edema (6.8 vs. 7.9 percent on warfarin). A numerically higher percentage of patient discontinuations occurred in each of the three betrixaban groups than in the open label warfarin group (8.7-9.4 vs. 6.3 percent).

For more information:,

Related Content

New FDA Proposed Rule Alters Informed Consent for Clinical Studies
News | Cardiovascular Clinical Studies | November 19, 2018
The U.S. Food and Drug Administration (FDA) is proposing to add an exception to informed consent requirements for...
A key slide from Elnabawi's presentation, showing cardiac CT plaque evaluations, showing the impact of psoriasis medication on coronary plaques at baseline and one year of treatment. It shows a reversal of vulnerable plaque development. #SCAI, #SCAI2018

A key slide from Elnabawi's presentation, showing cardiac CT plaque evaluations, showing the impact of psoriasis medication on coronary plaques at baseline and one year of treatment. It shows a reversal of vulnerable plaque development.  

Feature | Cardiovascular Clinical Studies | May 14, 2018
May 14, 2018 – New clinical evidance shows common therapy options for psoriasis (PSO), a chronic inflammatory skin di
Intravenous Drug Use is Causing Rise in Heart Valve Infections, Healthcare Costs. #SCAI, #SCAI2018
News | Cardiovascular Clinical Studies | May 14, 2018
May 14, 2018 — The opioid drug epidemic is impacting cardiology, with a new study finding the number of patients hosp
Patient Enrollment Completed in U.S. IDE Study of THERMOCOOL SMARTTOUCH SF Catheter
News | Cardiovascular Clinical Studies | March 15, 2018
March 15, 2018 –  Johnson & Johnson Medical Devices Companies announced today that Biosense Webster, Inc., who wo
Lexington Begins HeartSentry Clinical Trial
News | Cardiovascular Clinical Studies | February 20, 2018
February 20, 2018 – Lexington Biosciences, Inc., a development-stage medical device company, announced the commenceme
Endologix Completes Patient Enrollment in the ELEVATE IDE Clinical Study
News | Cardiovascular Clinical Studies | February 06, 2018
February 6, 2018 – Endologix, a developer and marketer of treatments for aortic disorders, announced the completion o
12-Month Results from Veryan Medical's MIMICS-2 IDE Study Presented at LINC
News | Cardiovascular Clinical Studies | February 01, 2018
February 1, 2018 – Thomas Zeller (Bad Krozingen, Germany) presented the 12-month results from Veryan Medical’s MIMICS
LimFlow Completes U.S. Feasibility Study Enrollment, Receives FDA Device Status
News | Cardiovascular Clinical Studies | February 01, 2018
February 1, 2018 –  LimFlow SA, developer of minimally-inv
ESC 2017 late breaking trial hot line study presentations.
News | Cardiovascular Clinical Studies | September 12, 2017
September 12, 2017 – The European Society of Cardiology (ESC) Congress 2017 includes several Hot Line Late-breaking C
U.K., NHS studies, weekend effect, hospital admission, atrial fibrillation, heart failure
News | Cardiovascular Clinical Studies | June 28, 2016
New research shows patients admitted to National Health Service (NHS) hospitals in the United Kingdom for atrial...
Overlay Init