Assessment of Anticoagulant Activity & Reversal of FactorXa Inhibitors
Research type
Research Study
Full title
Assessment of the Anticoagulant Activity of Factor Xa Inhibitors and their Reversal.
IRAS ID
165666
Contact name
Rebekah Ellen Fretwell
Contact email
Sponsor organisation
Sheffield Teaching Hospitals NHS Foundation Trust
Duration of Study in the UK
2 years, 0 months, 0 days
Research summary
There are several direct oral factor Xa inhibitors in development but only rivaroxaban and apixaban are licensed for thromboprophylaxis and/or treatment of venous thromboembolism and stroke prevention in atrial fibrillation (AF). Some Thrombin Generation Assays (TGA) show that rivaroxaban and apixaban have an important impact on how thrombin is generated, but more data is needed. New assays including Novel Hemostasis Assay (NHA) are being established but it is not known how these new drugs will impact on them.
Currently there is no antidote available for use in patients with major or life-threatening bleeding on rivaroxaban or apixaban. At the Royal Hallamshire Hospital (RHH) we provide a key service to other hospitals for patients with bleeding problems on these treatments as well as there being 300 patients on rivaroxaban and 200 on apixaban (numbers increasing all the time) at Sheffield Teaching Hospitals. Edoxaban recently had FDA approval for use in stroke prevention in deep vein thrombosis (DVT)/ pulmonary embolism (PE) prevention but has not had approval in the UK yet. If the drug is approved during the research period this will be included in the proposed study.
The primary aim is to set up NHA at RHH, and to investigate the effects that these two new anticoagulants have on TGA and NHA, and to determine which of these in vitro assays can be used to predict which reversal agents will work best (reversal agents will be tested on patient samples in vitro in the laboratory). The reversal agents used will be four factor prothrombin complex concentrate, three factor prothrombin complex concentrate, recombinant FVIIa (Novo seven®) and pure prothrombin.
A secondary aim will be to investigate standardisation of anti-Xa assays to measure drug effects, because this assay is used more widely than TG and NHA. Precise drug measurement with HPLC will also be optimised for implementation into routine use .REC name
South Central - Hampshire A Research Ethics Committee
REC reference
15/SC/0653
Date of REC Opinion
11 Dec 2015
REC opinion
Further Information Favourable Opinion