First Randomized Human Experience With Ticagrelor Reversal Agent - Ticagrelor Reversal Agent

Contribution To Literature:

The Ticagrelor Reversal Agent trial showed that PB2452 is safe and effective for prompt reversal of ticagrelor. 


The goal of the trial was to assess the safety and efficacy of PB2452 in reversing the antiplatelet effect of ticagrelor. 

Study Design

This was a phase 1 trial. Volunteers were assigned in 10 sequential cohorts in a 3:1 fashion to either PB2452 (n = 48) or placebo (n = 16). In cohort 1-3, PB2452 was administered as an intravenous infusion at a dose of 0.1 g, 0.3 g, or 1.0 g. In cohort 4-6, the dose was 1.0 g, 3.0 g, 9.0 g, and in cohorts 7-10, the dose was 18.0 g. Volunteers from cohorts 4-10 were pretreated with ticagrelor for 48 hours before receiving the study drug (loading dose of 180 mg followed by 90 mg BID).

  • Total number of enrollees: 64
  • Duration of follow-up: 48 hours
  • Mean volunteer age: 32 years
  • Percentage female: 42%

Inclusion criteria:

  • Healthy adults aged 18-50 years
  • Weight of 50-120 kg (110-265 lbs), body mass index 18-35 kg/m2

Exclusion criteria:

  • Contraindication to ticagrelor
  • Estimated glomerular filtration rate >60 ml/min/1.73 m2

Other salient features/characteristics:

  • White: 50%

Principal Findings:

Primary endpoint:

  • Duration of reversal was dose-dependent and lasted for 1-2 hours.
  • Multiple platelet function assays highlighted that PB2452 significantly reversed the antiplatelet effects of ticagrelor. Among the cohort that received initial bolus followed by extended infusion, reversal was noted within 5 minutes and was sustained for 20 hours.
  • Safety: Volunteers with any side effect: 35% for PB2452 vs. 12% for placebo; the majority were related to infusion site for PB2452 (bruising, extravasation).

Secondary endpoint:

  • No deaths in any of the arms.


The results of this phase 1 trial indicate that PB2452, a recombinant IgG1 monoclonal antibody antigen-binding fragment that binds with high affinity to ticagrelor and its active metabolite (AR-C124910XX), is safe and effective in reversing the antiplatelet effect of ticagrelor. The effect was dose dependent. Reversal was noted within 5 minutes with the higher initial bolus dose.

This drug may be potentially useful for patients where timely ticagrelor reversal is essential (significant bleeding, need for emergent surgery). This drug is not expected to work against clopidogrel and prasugrel, which are irreversible P2Y12 receptor inhibitors.


Bhatt DL, Pollack CV, Weitz JI, et al. Antibody-Based Ticagrelor Reversal Agent in Healthy Volunteers. N Engl J Med 2019;380:1825-33.

Presented by Dr. Deepak L. Bhatt at the American College of Cardiology Annual Scientific Session (ACC 2019), New Orleans, LA, March 17, 2019.

Keywords: ACC Annual Scientific Session, ACC19, Acute Coronary Syndrome, Adenosine, Anticoagulants, Blood Platelets, Healthy Volunteers, Immunoglobulin Fab Fragments, Immunoglobulin G, Infusions, Intravenous, Platelet Function Tests

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