Summary of selected studies of DOAC-specific reversal agents
| Drug name . | Clinical trial identifier . | Study name . | Study phase . | Study description . | No. of patients . | Results summary . |
|---|---|---|---|---|---|---|
| Ciraparantag | NCT02205905 | 1 | Open-label, single-dose, nonrandomized pharmacokinetic study in healthy male patients | 6 | Completed; results pending publication | |
| NCT01826266 | 1 | Double-blind RCT of efficacy/safety of escalating doses after single dose of edoxaban 60 mg | 80 | Administration of 100-300 mg reversed anticoagulation within 10-30 min and was sustained for 24 h | ||
| NCT02207257 | 2 | Single-blind RCT of safety/efficacy of escalating doses after steady-state edoxaban and effects after re-anticoagulation and second reversal | 69 | Recruiting as of second quarter of 2016 | ||
| Idarucizumab | NCT01688830 | 1 | Double-blind RCT in healthy patients for (A) an escalating dose assessment | 110 | (A) Rapid peak plasma exposure and elimination; no adverse effects. | |
| (B) For efficacy/safety | 47 | (B) Efficacy in reversal of coagulation test abnormalities (TT, dTT, aPTT, ECT) | ||||
| NCT01955720 | 1 | Double-blind RCT to study pharmacokinetics/pharmacodynamics | 12 | Reinitiation of dabigatran at 24 h led to similar aPTT levels whether previous treatment was idarucizumab or placebo | ||
| NCT02104947 | REVERSE-AD | 3 | Cohort study of efficacy/safety in patients with (A) serious bleeding on dabigatran who (B) required urgent procedure on dabigatran | 300 (planned) | Interim analysis (n = 90): dTT normalized in ≥93% and ECT normalized in ≥88% of patients. (A) median time for cessation of bleeding was 11.4 h; (B) normal intraoperative hemostasis was achieved in 92% of patients | |
| Andexanet alfa | NCT01758432 | 2 | Double-blind RCT to study pharmacokinetics/ pharmacodynamics | 144 | Dose-dependent reduction in factor Xa activity lasting until 2 h | |
| NCT02207725 | ANNEXA-A | 3 | Double-blind RCT of efficacy/safety in reversing apixaban | 48 | Anti-Xa activity reduced by 94%; thrombin generation restored in 100% | |
| NCT02220725 | ANNEXA-R | 3 | Double-blind RCT of efficacy/safety in reversing rivaroxaban | 53 | Anti-Xa activity reduced by 92%; thrombin generation restored in 96% | |
| NCT02329327 | ANNEXA-4 | 3B to 4 | Cohort study of efficacy/safety in achieving hemostasis in those with major bleeding on factor Xa inhibitors | 270 (planned) | Interim analysis (n = 67): anti-Xa activity reduced by 89% with rivaroxaban and 93% with apixaban; 79% had good/excellent hemostasis 12 h after infusion; 18% had thrombotic events |
| Drug name . | Clinical trial identifier . | Study name . | Study phase . | Study description . | No. of patients . | Results summary . |
|---|---|---|---|---|---|---|
| Ciraparantag | NCT02205905 | 1 | Open-label, single-dose, nonrandomized pharmacokinetic study in healthy male patients | 6 | Completed; results pending publication | |
| NCT01826266 | 1 | Double-blind RCT of efficacy/safety of escalating doses after single dose of edoxaban 60 mg | 80 | Administration of 100-300 mg reversed anticoagulation within 10-30 min and was sustained for 24 h | ||
| NCT02207257 | 2 | Single-blind RCT of safety/efficacy of escalating doses after steady-state edoxaban and effects after re-anticoagulation and second reversal | 69 | Recruiting as of second quarter of 2016 | ||
| Idarucizumab | NCT01688830 | 1 | Double-blind RCT in healthy patients for (A) an escalating dose assessment | 110 | (A) Rapid peak plasma exposure and elimination; no adverse effects. | |
| (B) For efficacy/safety | 47 | (B) Efficacy in reversal of coagulation test abnormalities (TT, dTT, aPTT, ECT) | ||||
| NCT01955720 | 1 | Double-blind RCT to study pharmacokinetics/pharmacodynamics | 12 | Reinitiation of dabigatran at 24 h led to similar aPTT levels whether previous treatment was idarucizumab or placebo | ||
| NCT02104947 | REVERSE-AD | 3 | Cohort study of efficacy/safety in patients with (A) serious bleeding on dabigatran who (B) required urgent procedure on dabigatran | 300 (planned) | Interim analysis (n = 90): dTT normalized in ≥93% and ECT normalized in ≥88% of patients. (A) median time for cessation of bleeding was 11.4 h; (B) normal intraoperative hemostasis was achieved in 92% of patients | |
| Andexanet alfa | NCT01758432 | 2 | Double-blind RCT to study pharmacokinetics/ pharmacodynamics | 144 | Dose-dependent reduction in factor Xa activity lasting until 2 h | |
| NCT02207725 | ANNEXA-A | 3 | Double-blind RCT of efficacy/safety in reversing apixaban | 48 | Anti-Xa activity reduced by 94%; thrombin generation restored in 100% | |
| NCT02220725 | ANNEXA-R | 3 | Double-blind RCT of efficacy/safety in reversing rivaroxaban | 53 | Anti-Xa activity reduced by 92%; thrombin generation restored in 96% | |
| NCT02329327 | ANNEXA-4 | 3B to 4 | Cohort study of efficacy/safety in achieving hemostasis in those with major bleeding on factor Xa inhibitors | 270 (planned) | Interim analysis (n = 67): anti-Xa activity reduced by 89% with rivaroxaban and 93% with apixaban; 79% had good/excellent hemostasis 12 h after infusion; 18% had thrombotic events |
RCT, randomized controlled trial.