ENVISAGE TAVI-AF
Research type
Research Study
Full title
EDOXABAN VERSUS STANDARD OF CARE AND THEIR EFFECTS ON CLINICAL OUTCOMES IN PATIENTS HAVING UNDERGONE TRANSCATHETER AORTIC VALVE IMPLANTATION – IN ATRIAL FIBRILLATION
IRAS ID
221444
Contact name
Simon Redwood
Contact email
Sponsor organisation
Daiichi Sankyo Europe GmbH
Eudract number
2016-003930-26
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 1 months, 0 days
Research summary
Research Summary
Narrowing of the aortic valve is the second most common valvular disorder in the EU/US. Transcathether Aortic Valce Implantation (TAVI) is a procedure where a new valve is placed in the location of the old and narrow aortic valve. Following this procedure, there is an increased risk for bleeding complications and cerebrovascular events, for example stroke.
Therefore, balancing the risk of bleeding and thrombotic events is extremely important. These risks are partly mitigated by the use of blood thinners which include anticoagulants and antiplatelets. Anticoagulants, such as edoxaban or vitamin-K antagonists (VKA) such as warfarin, and antiplatelet drugs, such as Acetyl Salicylic Acid (ASA) (e.g., aspirin) and the drugs called P2Y12 inhibitors (e.g., clopidogrel), which prevent platelets from clumping together to form a clot.
Edoxaban has been developed as an alternative to VKA and has already been approved for clinical use in several countries for the prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation with one or more risk factors, such as congestive heart failure, high blood pressure, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack (TIA). It has been demonstrated that Edoxaban is safer than VKA in its approved use.
In this study Edoxaban alone or in combination with aspirin and/or a P2Y12 inhibitor will be compared to a VKA alone or in combination with aspirin and/or a P2Y12 inhibitor. The treatments will be compared for safety with regard to bleeding and effectiveness with regard to thrombotic complications like stroke in patients who have atrial fibrillation AND have undergone a successful TAVI.
This study will be conducted at specialised TAVI sites in across the UK. The study is planned to last 3 years.Summary of Results
The ENVISAGE-TAVI AF trial is a multinational, multicenter, prospective, randomized, open-label, blinded end point evaluation study comparing Edoxaban, an oral reversible Factor Xa inhibitor, to vitamin K antagonists (VKA) in patients with atrial fibrillation and an indication for chronic oral anticoagulation after successful TAVI.
A total of 1426 participants were enrolled in the clinical study, participants were randomization to receive either the study drug Edoxaban or the comparator drug VKA. 713 participants were randomised to Edoxaban and another 713 to the VKA treatment group. 692 participants received at least one dose of the study drug Edoxaban compared to 685 subjects receiving at least one dose of VKA. A total of 526 subjects on Edoxaban completed the entire study including safety follow-up compared with 475 on VKA. Overall, the average age was 82.1 years and 47.5% of participants were women.
The study was completed on 4th March 2021 with official database lock on 31st March 2021.The primary effectiveness endpoint was the incidence of net adverse clinical events (NACE) such as strokes or bleeding or example, the composite of all-cause death, myocardial infarction (heart attack), ischemic stroke, systemic embolic event (blood clots), valve thrombosis, and major bleeding. The primary safety endpoint was the incidence of major bleeding. All clinical events were adjudicated by an independent Clinical Events Committee. An independent data safety and monitoring board monitored study progress and clinical results. A total of 1,426 patients from 173 centres in 14 countries and 3 continents were enrolled in the trial, and 713 patients were assigned to each treatment arm. Clinical follow-up ended in January 2021 when a total of 327 NACE events occurred.
The Edoxaban-based vs the VKA-based therapy met the primary endpoint for non-inferiority of net adverse clinical events (NACE). The Edoxaban-based vs the VKA-based therapy missed the primary safety endpoint of major bleeding.
Study results conclusions:
ENVISAGE-TAVI AF compared an Edoxaban-based vs a VKA based therapy for the primary endpoint of net adverse clinical events (NACE), i.e., the composite of all-cause death, ischemic stroke, systemic embolism, myocardial infarction, valve thrombosis, and major bleeding and for the primary safety endpoint of major bleeding.
With 327 NACE events, the endpoint driven study reached its target of 320 NACEs.
VKA therapy was well managed with time in therapeutic range, the baseline characteristics between the treatments did not differ.
The Edoxaban-based vs the VKA-based therapy met the primary endpoint for non-inferiority of NACE.
The Edoxaban-based vs the VKA-based therapy missed the primary safety endpoint of major bleeding for non-inferiority with a higher annual event rate for major gastrointestinal bleeding but a numerically lower annual event rate for intracranial (within the skull) hemorrhage. Fatal bleeding was similar between both treatments.
In summary:
In AF patients after successful TAVI, Edoxaban-based therapy was non-inferior to well managed VKA-based therapy for NACE events with numerically lower rates of all-cause death, ischemic stroke, and intracranial hemorrhage (ICH) but higher rates for major bleeding that were mainly driven by non-fatal major gastrointestinal (GI) bleeding.
Edoxaban compared with VKA showed
• a trend for lower risks of ischemic events (where a part of the body is not getting enough blood) and all-cause death
• a higher risk of major GI bleeding but a lower risk of ICHREC name
West of Scotland REC 1
REC reference
17/WS/0072
Date of REC Opinion
16 May 2017
REC opinion
Further Information Favourable Opinion