5-Minute Point-of-Care Anti-Factor Xa Test for Emergent Patient Management - ABSTRACT We are proposing to develop a multiplexed point-of-care anti-factor Xa (anti-Xa) and hemoglobin test to guide emergent management of bleeding and strokes in patients on anti-Xa direct oral anticoagulants (DOACs). This includes guiding appropriate treatment with andexanet alfa (andexanet, tradename ANDEXXA) during bleeds or thrombolytics for acute ischemic stroke (AIS). In this Direct-to-Phase II (D2P2) effort, we will leverage our proprietary CE-marked FXa fluorogenic substrate and our rHEALTH point-of-care device and app to develop a point-of-care (POC) test that yields results for both drug-specific anti-Xa activity and hemoglobin. The CLIA-waivable approach will feature a 5-minute turnaround time, from sample collection to result, delivering results 10x faster than any current STAT central lab test. This would lead to quicker delivery of life-saving interventions. Currently about 16 million individuals are on direct oral anticoagulants, predominantly for nonvalvular atrial fibrillation, and ~500,000 per year are hospitalized with bleeds or breakthrough strokes. Proper therapeutic treatment require emergent and rapid measurement of anti-Xa activity. In preliminary Phase I-like work, we have developed three innovations: (1) an ultra-rapid anti-Xa assay based on our CE-marked FXa substrate, (2) a 5-minute sample-to-answer 4D microfluidic cartridge that carries out sequential steps of our anti-Xa assay, and (3) an app-connected point-of-care device that returns both the anti-Xa and hemoglobin values for venous or capillary blood samples. Here we propose to leverage this work to develop a system that will rigorously test thousands of cartridges across three aims: (1) Assess accuracy and precision of all consumable steps and improve robustness where needed, (2) Assess performance of various anti-Xa drugs on spiked whole blood samples and develop drug-specific controls and calibrators, and (3) Characterize the integrated anti-Xa monitoring device, app, and consumable for analytical precision, interferences, ranges, and limit of detection. Upon completion of this D2P2, we will commence a 510k clinical validation study, as required for FDA clearance. The success of developing a 5-minute anti-Xa test will allow for 10x faster responses to guide emergency management of patients and bring a much-needed capability to the point-of-care. A patient’s presenting anti-Xa drug levels can vary widely, based on their peak and trough timing, drug dosage, drug clearance rate, and bioavailability. A 5-minute anti-Xa test allows guiding immediate management and timely follow-on measurements to allow tailored therapy. The rapid and cost-effective nature of the device will allow its use in ambulances, emergency rooms, and surgical suites. The simultaneous reporting of hemoglobin gives treating clinicians immediate information about the status of blood loss in the event of bleeding. The results of our efforts will be a rapid, cost-effective, monitoring device, consumable, app, and controls that will provide an urgently needed resource in light of recent developments in anti-Xa therapies.
