Accuracy of a Rapid Diagnostic Test for the Presence of Direct Oral Factor Xa or Thrombin Inhibitors in Urine-A Multicenter Trial.

The rapid determination of the presence of direct oral anticoagulants (DOACs) in a patient remains a major challenge in emergency medicine and for rapid medical treatment decisions. All DOACs are excreted into urine. A sensitive and specific point-of-care test has been developed to determine whether they are present in patient urine samples. This prospective multicenter study aimed to demonstrate at least 95% correct positive and negative predictive results for factor Xa and thrombin inhibitors in urine samples using DOAC Dipstick pads compared with liquid chromatography-tandem mass spectrometry (LC-MS/MS) (NCT03182829). Nine hundred and fourteen subjects were included and 880 were evaluated per protocol (factor Xa inhibitors apixaban, edoxaban, and rivaroxaban: n  = 451, thrombin inhibitor dabigatran: n  = 429) at 18 centers. The sensitivity, specificity, accuracy, and predictive values and agreement between methods for determination of factor Xa inhibitors were at least noninferior to 95% with a 0.5% margin and of thrombin inhibitor superior to 97.5%. These results were compared with LC-MS/MS results in the intention-to-analyze cohort (all p  < 0.05). The receiver operating curve showed c -values of 0.989 (factor Xa inhibitors) and 0.995 (thrombin inhibitor). Visual evaluation of the factor Xa and thrombin inhibitor pads was not different between centers. Qualitative determination of both types of DOACs was accurate using the DOAC Dipstick compared with using LC-MS/MS. The high predictive values may impact laboratory and clinical decision-making processes.
Competing Interests: J.H. is managing director and founder of DOASENSE and reports personal fees from Portola, outside the submitted work; a patent US 9,133,501 licensed, a patent EU 2643475 licensed, a patent US 9,944,971 licensed, and a patent EU 2723886 licensed. J.B.W. reports grants and personal fees from Bayer, grants and personal fees from Daiichi Sankyo, grants and personal fees from DOASENSE, grants and personal fees from Portola, grants from Pfizer, during the conduct of the study. P.V. reports grants and personal fees from Bayer, Boehringer Ingelheim, BMS, Pfizer, Daiichi-Sankyo and Portola, outside the submitted work. J.D. is the CEO and founder of QUALIblood and reports personal fees from Diagnostica Stago, Roche, Roche Diagnostics, Portola, and Daiichi-Sankyo, outside the submitted work. C.W. reports research grant and consultancy from DOASENSE during the conduct of the study. S.H. reports research grant from DOASENSE during the conduct of the study. M.C. reports grants and other from Bayer, personal fees from Shionogi, Alexion, Pfizer, Octapharma, BMS Canada, CSL Behring, Servier Canada, Diagnostica Stago, and Asahi Kasei, outside the submitted work; grants from Leo Pharma and Heart and Stroke Foundation, and other from Daiichi and Alnylam. I.E. reports grants and personal fees from Stago, Boehringer-Ingelheim, Bayer, Pfizer, Bristol Myers Squibb, during the conduct of the study; grants and personal fees from Stago, Boehringer Ingelheim, Pfizer, Bristol Myers Squibb, Bayer, outside the submitted work. R.B. reports personal fees from DOASENSE GmbH, during the conduct of the study; personal fees from Bayer AG, BMS, Daichii-Sankyo, Pfizer, outside the submitted work.
(Georg Thieme Verlag KG Stuttgart · New York.)