@article{MRA, author = {Edelgard Lindhoff-Last and Jack Ansell}, title = { Reversal of Direct Oral Anticoagulants: Meeting a Need & Filling a Gap}, journal = {Medical Research Archives}, volume = {11}, number = {7.1}, year = {2023}, keywords = {}, abstract = {Presently, three reversal strategies are available to reverse the anticoagulant activity of the direct oral anticoagulants, each with various limitations or drawbacks. A new reversal agent that addresses some of these limitations or gaps in therapy is in advanced clinical trials. Ciraparantag is a small molecule specifically designed to bind non-covalently by charge-charge interaction to unfractionated heparin and low molecular weight heparin. It shows similar binding characteristics to the direct oral anticoagulants with no off-target binding of selected proteins or commonly used drugs demonstrated to date. Ciraparantag reaches maximum concentration within minutes following intravenous administration with a half-life of 12 – 19 minutes. It is primarily hydrolyzed by serum peptidases into two metabolites, neither of which has substantial activity. Ciraparantag and its metabolites are recovered almost entirely in the urine. In animal models of bleeding a single intravenous dose of ciraparantag given at peak concentrations of an anticoagulant significantly reduces blood loss. In Phase 1/2 clinical trials, ciraparantag restores coagulation in direct oral anticoagulant-treated healthy volunteers with in minutes with a sustained effect over 24 hours. The drug is well tolerated with minor side effects, the most common of which is a flush or sensation of warmth after administration. As a phase 3 trial is in preparation to clinically prove its effectiveness, ciraparantag appears to address many of the short-comings of current reversal strategies.  }, issn = {2375-1924}, doi = {10.18103/mra.v11i7.1.4004}, url = {https://esmed.org/MRA/mra/article/view/4004} }