RIDGEFIELD, Conn., Sept. 13 /PRNewswire/ — Boehringer Ingelheim today
announced that the September 15 issue of The Lancet will publish results from
the RE-NOVATE study, which investigated dabigatran etexilate as a potential
therapy for patients undergoing total hip replacement surgery(1). The results
from this study demonstrate that both doses (220mg and 150mg) of the oral direct
thrombin inhibitor, dabigatran etexilate, administered for a median of 33 days,
were non-inferior to injectable enoxaparin in reducing the risk of venous
thromboembolism (VTE) after total hip replacement surgery with similar safety.
The primary endpoint of this trial was a composite consisting of total venous
thromboembolic events and all-cause mortality during treatment, which occurred
in 6.0% of the 220mg group and 8.6% of the 150mg group taking dabigatran
etexilate, versus 6.7% of the enoxaparin group. Importantly, a pre-specified
secondary outcome of major venous thromboembolism and venous thromboembolism-related
mortality was also similar between groups, occurring in 3.1% of the 220mg group
and 4.3% of the 150mg group taking dabigatran etexilate, versus 3.9% of the
Anticoagulation-related bleeding is the primary safety concern during hip
replacement surgery, since major bleeding into the replaced joint can have a
detrimental impact on clinical outcome(2). Generally, few major bleeding events
were reported, occurring at 2.0% in the 220mg group and 1.3% in the 150mg group
for dabigatran etexilate, versus 1.6% in the enoxaparin group. Notably about
half of all major bleeding events started after surgery and before the first
dose of dabigatran etexilate. There were no major bleeding events reported after
hospital discharge in the dabigatran etexilate groups.
Data from frequent liver function monitoring showed that the frequency of
increases in liver enzyme concentrations with dabigatran etexilate is low during
the entire extended treatment period. Results showed that alanine
aminotransferase (ALT) elevation greater than three times the upper limit of
normal occurred in 5.3% enoxaparin group, as compared to 3.0% in the 150mg group
and 3.0% in the 220mg group taking dabigatran etexilate. Similarly, the
incidence of acute coronary events was low, with no significant differences
between all groups.
Current treatment guidelines recommend that patients undergoing knee or hip
replacement surgery receive thromboprophylaxis (treatment to prevent VTE) with
low molecular weight heparin (LMWH), fondaparinux or warfarin for at least 10
days after surgery. For patients undergoing hip replacement surgery, extended
thromboprophylaxis for up to 28-35 days is recommended.(3) The RE- NOVATE study
was designed consistent with these guidelines.
About dabigatran etexilate
Dabigatran etexilate is an investigational oral direct thrombin inhibitor
that specifically and reversibly inhibits thrombin, the key enzyme for blood
clot formation, and is currently in phase 3 development. In the RE-NOVATE study,
dabigatran etexilate was dosed once a day without routine coagulation
monitoring. Patients in the study received a fixed dose of dabigatran etexilate
and were not titrated during the duration of the study.
Further studies investigating dabigatran etexilate
Dabigatran etexilate is being investigated in multiple phase 3 trials that
are designed to investigate the oral direct thrombin inhibitor as a potential
treatment and prophylaxis for several thromboembolic disease conditions. The
phase 3 clinical trial program is expected to involve more than 27,000 patients
from Asia, Australia, Europe, the Americas, and South Africa.
Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the
largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and
a member of the Boehringer Ingelheim group of companies.
The Boehringer Ingelheim group is one of the world’s 20 leading
pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates
globally with 137 affiliates in 47 countries and approximately 38,400 employees.
Since it was founded in 1885, the family-owned company has been committed to
researching, developing, manufacturing and marketing novel products of high
therapeutic value for human and veterinary medicine.
In 2006, Boehringer Ingelheim posted net sales of US $13.3 billion (10.6
billion euro) while spending approximately one-fifth of net sales in its largest
business segment, Prescription Medicines, on research and development. For more
information, please visit http://us.boehringer-ingelheim.com.
1. Lancet ref
2. Lotke PA, Lonner JH. Deep venous thrombosis prophylaxis: better living
through chemistry-in opposition. J Arthroplasty 2005;20:15-7
3. Geerts WH, Pineo GF, Heit JA et al. Prevention of Venous
Thromboembolism: The Seventh ACCP Conference on Antithrombotic and
Thrombolytic Therapy. Chest 2004;126:338-400