Rationale and design of PROACT Xa: A randomized, multicenter, open-label, clinical trial to evaluate the efficacy and safety of apixaban versus warfarin in patients with a mechanical On-X Aortic Heart Valve - 25/08/20
, Tracy Y. Wang, MD MHS MSc a, Renato D. Lopes, MD PhD a, Alma Chavez, BSN a, Brittanny Boyer, BS CCRP c, Hwasoon Kim, PhD a, Kevin J. Anstrom, PhD a, Richard C. Becker, MD d, Eugene Blackstone, MD e, Marc Ruel, MD MPH f, Vinod H. Thourani, MD g, John D. Puskas, MD h, Marc W. Gerdisch, MD i, Douglas Johnston, MD e, Scott Capps, MS c, John H. Alexander, MD MHS a, Lars G. Svensson, MD PhD eBackground |
Vitamin K antagonists are the only approved oral anticoagulants for long-term prophylaxis against valve thrombosis and thromboembolism in patients with a mechanical heart valve. Despite the proven efficacy and safety of anticoagulation with the oral direct factor Xa inhibitor apixaban compared with warfarin in high-risk populations including subjects with atrial fibrillation or with venous thromboembolism, it remains unknown whether patients with a mechanical heart valve can be safely managed with apixaban. The On-X Aortic Heart Valve and On-X Ascending Aortic Prosthesis with the Vascutek Gelweave Valsalva Graft may have lower rates of valve thrombosis and thromboembolism than conventional bileaflet and tilting disc valves due its unique pyrolytic carbon composition and flared inlet design.
Design |
PROACT Xa is a randomized, multicenter, open-label, active-controlled trial comparing apixaban with warfarin in patients with an On-X Aortic Heart Valve or On-X Ascending Aortic Prosthesis with the Vascutek Gelweave Valsalva Graft. The study will randomize approximately 1,000 patients from approximately 60 sites in North America who underwent aortic valve replacement at least 3 months prior. Patients will be randomized 1:1 to receiving apixaban 5 mg twice daily or warfarin with a target international normalized ratio of 2.0-3.0. The last randomized participant will be followed for at least 2 years. The primary efficacy outcome is the composite of valve thrombosis and valve-related thromboembolism, and the primary safety outcome is major bleeding. Assuming the primary outcome occurs in warfarin-anticoagulated patients at a rate of 1.75%/patient-year, the study has more than 90% power to assess noninferiority of apixaban treatment with an absolute noninferiority margin of 1.75%/patient-year. A second co-primary analysis is to compare the hazard rate for the apixaban arm to twice the objective performance criterion for thromboembolism and valve thrombosis, that is, 3.4%/patient-year.
Summary |
PROACT Xa will determine whether patients with an On-X Aortic Heart Valve can be anticoagulated with apixaban as an alternative to warfarin.
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| ☆ | Disclosures: O. K. J.: none. T. Y. W.: research grants to the Duke Clinical Research Institute from AstraZeneca, Bristol Myers Squibb, Cryolife, Chiesi, Portola, and Regeneron, as well as consulting honoraria from AstraZeneca, Sanofi, and Cryolife. R. D. L.: grants and personal fees from Bristol-Myers Squibb and Pfizer; personal fees from Boehringer Ingelheim and Bayer AG; and grants from Amgen Inc, GlaxoSmithKline, Medtronic PLC, and Sanofi Aventis outside the submitted work. A. C.: none. B. B.: CryoLife. H. K.: none. K. J. A.: research funding from Merck, Bayer, and NIH. R. C. B.: scientific advisory board for Janssen; DSMB committees for Ionis Pharmaceuticals, Akcea Therapeutics, and Novartis; and research funding from NIH and American Heart Association. E. B.: none. M. R.: none. V. H. T.: advisor/research, CryoLife. JDP: none. M. W. G.: consultant, CryoLife. D. J.: consulting for Edwards Lifesciences and educational honoraria from LivaNova. S. C.: CryoLife. JHA: research funding from Bayer, Bristol Myers Squibb, CryoLife, and XaTek and consulting or honorarium from Bayer, Bristol Myers Squibb, CryoLife, Pfizer, and XaTek. L. G. S.: unpaid member of PARTNER Executive committee and Chairman of the Writing Committee. |
| ☆☆ | T. Y. W., R. D. L., H. K., R. C. B., E. B., M. R., V. H. T., J. D. P., M. W. G., D. J., J. H. A., and L. G. S. are members of the PROACT Xa clinical trial steering committee. |
| ☆☆☆ | Ismail El-Hamamsy, MD, PhD, served as guest editor for this article. |
Vol 227
P. 91-99 - septembre 2020 Retour au numéro
Article précédent
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