What is the clinical evidence from this study?

Study design: RCT. Population: Rivaroxaban-induced anticoagulation (n=18). Intervention: Andexanet alfa vs. Placebo. Primary outcome: Reversal of the anticoagulant activity of rivaroxaban (anti-fXa activity).

What question did this study set out to answer?

To investigate the efficacy and safety of andexanet alfa in reversing rivaroxaban-induced anticoagulation.

November 15, 2013Blood

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial Demonstrating Reversal Of Rivaroxaban-Induced Anticoagulation In Healthy Subjects By Andexanet Alfa (PRT064445), An Antidote For Fxa Inhibitors

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Key result

Andexanet alfa dose-dependently decreased anti-fXa activity by 20% (210 mg) and 53% (420 mg) from pre-treatment levels, partially reversing rivaroxaban-induced anticoagulation in healthy subjects.

Why the study?

Does andexanet alfa reverse the anticoagulant effects of rivaroxaban in healthy subjects?

Population

Healthy subjects (n=18 reported for the first 2 cohorts)

Comparison

Andexanet alfa 210 mg or 420 mg administered… vs Placebo administered intravenously on Day 6, 3…

Design

RCT, 6:3 ratio of AnXa to placebo per cohort, double-blind, placebo-controlled

Follow-up

Through Day 48 for pharmacodynamic and safety data

Authors

MCMark CrowtherMcMaster University MMM. Manasar.Vandana MKMichael KittPortola Pharmaceuticals (United States)

Discussion

Member takes

Implication

Andexanet alfa may enable targeted reversal of fXa inhibitors; leaves open its clinical efficacy and safety pending confirmatory trials.

Key Points

To investigate the efficacy and safety of andexanet alfa in reversing rivaroxaban-induced anticoagulation.
Phase 2 randomized, double-blind, placebo-controlled trial
Healthy subjects received rivaroxaban for 6 days and andexanet alfa on Day 6
Data collected up to Day 48, with pharmacokinetics assessed until Day 10.
After 210 mg and 420 mg doses of andexanet alfa, anti-fXa activity decreased by 20% and 53%, respectively
Unbound rivaroxaban plasma concentrations decreased by 32% and 51% post-treatment
No serious adverse events; mild infusion-related reactions were reported.

Study Design

Type

RCT (n=18)

Blinding

Double-blind

Randomization

6:3 ratio

Structured PICO

Does andexanet alfa reverse the anticoagulant effects of rivaroxaban in healthy subjects?

Population

18 healthy subjects treated with rivaroxaban 20 mg daily for 6 days to assess anticoagulation reversal by andexanet alfa.

Intervention

Andexanet alfa (AnXa) 210 mg or 420 mg administered intravenously on Day 6, 3 hours after the last dose of rivaroxaban (20 mg oral qd for 6 days)

Comparator

Placebo administered intravenously on Day 6, 3 hours after the last dose of rivaroxaban

Outcome

Reversal of anticoagulant activity of rivaroxaban (anti-fXa activity, unbound rivaroxaban plasma concentrations, thrombin generation, prothrombin time, and activated clotting time)surrogate

Andexanet alfa dose-dependently reverses the anticoagulant effects of rivaroxaban in healthy subjects, supporting its development as a specific antidote for factor Xa inhibitors.

Cite This Study

Crowther et al. (2013) conducted an RCT in Rivaroxaban-induced anticoagulation (n=18). Andexanet alfa vs. Placebo was evaluated on Reversal of the anticoagulant activity of rivaroxaban (anti-fXa activity). Andexanet alfa dose-dependently decreased anti-fXa activity by 20% (210 mg) and 53% (420 mg) from pre-treatment levels, partially reversing rivaroxaban-induced anticoagulation in healthy subjects.

synapsesocial.com/papers/6a62a4c00582df600cc3d0c0 https://doi.org/10.1182/blood.v122.21.3636.3636

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A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial Demonstrating Reversal Of Rivaroxaban-Induced Anticoagulation In Healthy Subjects By Andexanet Alfa (PRT064445), An Antidote For Fxa Inhibitors

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Cite This Study

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial Demonstrating Reversal Of Rivaroxaban-Induced Anticoagulation In Healthy Subjects By Andexanet Alfa (PRT064445), An Antidote For Fxa Inhibitors

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Cite This Study

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