Comparison of a direct Factor Xa inhibitor, edoxaban, with dalteparin and ximelagatran: A randomised controlled trial in healthy elderly adults.

15:42 EDT 25th October 2014 | BioPortfolio

Summary of "Comparison of a direct Factor Xa inhibitor, edoxaban, with dalteparin and ximelagatran: A randomised controlled trial in healthy elderly adults."


INTRODUCTION:
Edoxaban (the free base of DU-176b) is a new, oral direct Factor Xa inhibitor. This is the first study to compare the hemostatic response to edoxaban, ximelagatran, and dalteparin in healthy, elderly adults. MATERIALS AND
METHODS:
In this open-label, active-controlled clinical trial, 40 adults (65-75years), were randomised to: oral edoxaban (60mg, twice-daily, 7 doses), subcutaneous dalteparin (5000IU, once-daily, 4 doses), oral ximelagatran (24mg, twice-daily, 7 doses) or no drug. Blood samples were taken before, and 1.5, 4, 12, 24, 72, 84, 96, 108, 120, and 144 hours after, the first dose. The primary outcomes were changes in thrombin-antithrombin complex, prothrombin fragment 1+2 and D-dimer, and adverse events. Additional biomarkers of coagulation, and endothelial cell and platelet activation were compared (ANOVA).
RESULTS:
All subjects completed the study. Inhibition of thrombin generation lag time, peak, and constant velocity index were significantly greater, and extended for a longer period of time, following edoxaban administration, compared with dalteparin. We found that the traditional assay for anti-FXa activity was not appropriate for the new anticoagulants. Biomarker changes following edoxaban administration (including prolongation of prothrombin time) reflected inhibition of Factor Xa; there was no effect on platelet, tissue factor or endothelial activation. There were no clinically significant changes in primary outcomes. No serious adverse events were reported.
CONCLUSION:
Oral administration of edoxaban resulted in effective Factor Xa and TG inhibition, and was well-tolerated. Studies are needed to confirm edoxaban (60mg daily) use in clinical practice.
SPONSORSHIP:
Daiichi Sankyo Pharma Development.

Affiliation

Biomnis, 78 Avenue de Verdun, 94208 Ivry-sur-Seine Cedex, France.

Journal Details

This article was published in the following journal.

Name: Thrombosis research
ISSN: 1879-2472
Pages:

Links

PubMed Articles [16250 Associated PubMed Articles listed on BioPortfolio]

Impact of nonsynonymous mutations of factor X on the functions of factor X and anticoagulant activity of edoxaban.

Edoxaban is an oral direct factor Xa (FXa) inhibitor and its efficacy as an oral anticoagulant is less subject to drug-food and drug-drug interaction than existing vitamin K antagonists. Although this...

Edoxaban Transport Via P-glycoprotein is a Key Factor for the Drug Disposition.

Edoxaban (free base of DU-176b), an oral direct factor Xa inhibitor, is mainly excreted unchanged into urine and feces. Since active membrane transport processes such as active renal secretion, biliar...

Perioperative management and therapy of bleeding complications.

The new oral anticoagulants directly inhibit either thrombin (Dabigatran, Pradaxa®,) or activated Factor X (rivaroxaban, Xarelto®, and apixaban, Eliquis®) and have been approved for thromboprophyla...

Edoxaban versus warfarin for stroke prevention in non-valvular atrial fibrillation: a cost-effectiveness analysis.

Edoxaban, an oral direct factor Xa inhibitor, has been found non-inferior to warfarin for preventing stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF), with a lower...

Population Pharmacokinetic-Pharmacodynamic Modeling Analysis of Intrinsic FXa and Bleeding From Edoxaban Treatment.

Edoxaban is an oral, once-daily, direct factor Xa (FXa) inhibitor that has been evaluated for the prevention of stroke in patients with atrial fibrillation (AF) and for the treatment and prevention of...

Clinical Trials [3482 Associated Clinical Trials listed on BioPortfolio]

Comparative Investigation of Low Molecular Weight (LMW) Heparin/Edoxaban Tosylate (DU176b) Versus (LMW) Heparin/Warfarin in the Treatment of Symptomatic Deep-Vein Blood Clots and/or Lung Blood Clots. (The Edoxaban Hokusai-VTE Study).

Evaluation of heparin/edoxaban tosylate (DU176b) versus heparin/warfarin in preventing recurrence of blood clots in patients with acute symptomatic deep-vein blood clots in the legs and/or...

A Comparison of Dalteparin and Tinzaparin for Prevention of Blood Clots in Hemodialysis Patients on Oral Anticoagulants Having Surgery

The purpose of this study is to better understand if either dalteparin or tinzaparin is a better drug to use in dialysis patients on blood thinners who are at high risk of developing blood...

Long Term Open Follow-up With H376/95 vs. Warfarin

The purpose of this study is to evaluate tolerability of long-term treatment with ximelagatran compared to standard treatment with warfarin.

Dalteparin in Combination With Sunitinib in Patients With Metastatic Kidney Cancer

To determine the recommended dosage of Sunitinib and Dalteparin in patients with metastatic renal cell cancer. To evaluate the safety and tolerability of combination of Sunitinib and Dalte...

Dalteparin in Preventing Blood Clots in Patients With Lung Cancer

RATIONALE: Anticoagulants, such as dalteparin, may help prevent blood clots from forming in patients with lung cancer. It is not yet known whether dalteparin is effective in preventing blo...

Medical and Biotech [MESH] Definitions

Comparison of various psychological, sociological, or cultural factors in order to assess the similarities or diversities occurring in two or more different cultures or societies.

A specificity protein transcription factor that regulates expression of a variety of genes including VASCULAR ENDOTHELIAL GROWTH FACTOR and CYCLIN-DEPENDENT KINASE INHIBITOR P27.

A COUP transcription factor that was originally identified as a homodimer that binds to a direct repeat regulatory element in the chicken albumin promoter. It is a transcription factor that plays an important role in EMBRYONIC DEVELOPMENT of the CENTRAL NERVOUS SYSTEM.

Activated form of factor VIII. The B-domain of factor VIII is proteolytically cleaved by thrombin to form factor VIIIa. Factor VIIIa exists as a non-covalent dimer in a metal-linked (probably calcium) complex and functions as a cofactor in the enzymatic activation of factor X by factor IXa. Factor VIIIa is similar in structure and generation to factor Va.

Activated form of factor XI. In the intrinsic pathway, Factor XI is activated to XIa by factor XIIa in the presence of cofactor HMWK; (HIGH MOLECULAR WEIGHT KININOGEN). Factor XIa then activates factor IX to factor IXa in the presence of calcium.

Search BioPortfolio:
Loading