What question did this study set out to answer?

To evaluate the efficacy of descending doses of 4-factor prothrombin complex concentrate (4F-PCC) in reversing the anticoagulant effects and biomarker alterations induced by edoxaban.

November 18, 2014Circulation

Edoxaban Effects on Bleeding Following Punch Biopsy and Reversal by a 4-Factor Prothrombin Complex Concentrate

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Healthy subjects (n=110). Intervention: 4-factor prothrombin complex concentrate (4F-PCC) vs. Placebo. Primary outcome: Bleeding duration and bleeding volume.

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Key result

Intravenous 4F-PCC dose-dependently reversed edoxaban's effects on bleeding duration and endogenous thrombin potential, with complete reversal at 50 IU/kg.

Why the study?

Does 4-factor prothrombin complex concentrate reverse the bleeding effects and biomarker changes induced by edoxaban in healthy subjects?

Population

110 healthy subjects (17 in part 1, 93 in part 2)

Comparison

Intravenous administration of 4-factor… vs Placebo following administration of edoxaban

Design

RCT, randomized (2-way crossover), double-blind

Authors

HZHamim ZahirBiogen (United States)KBKaren BrownUniversity of Leicester AVAlexander G. VandellDaiichi Sankyo (United States)

Discussion

Member takes

Implication

Supports 4F-PCC for edoxaban reversal in bleeding; extends reversal data to this NOAC in RCT.

Key Points

To evaluate the efficacy of descending doses of 4-factor prothrombin complex concentrate (4F-PCC) in reversing the anticoagulant effects and biomarker alterations induced by edoxaban.
Conducted a single-center, double-blind, randomized, placebo-controlled, 2-way crossover phase 1 study (NCT02047565).
Treated 110 healthy subjects (17 in part 1, 93 in part 2) with oral edoxaban (60 mg) followed by intravenous 4F-PCC (50, 25, or 10 IU/kg) or placebo.
Assessed punch biopsy bleeding duration and volume alongside coagulation biomarkers, including endogenous thrombin potential and prothrombin time.
Intravenous 4F-PCC dose-dependently reversed edoxaban-induced increases in bleeding duration and endogenous thrombin potential, achieving complete reversal at 50 IU/kg.
Prothrombin time was partially reversed at 50 IU/kg 4F-PCC, and a similar reversal trend occurred for bleeding volume.
Edoxaban administered alone and in combination with 4F-PCC was safe and well tolerated across all cohorts.

Study Design

Type

RCT (n=110)

Blinding

Double-blind

Randomization

randomized

Multicenter

Structured PICO

Does 4-factor prothrombin complex concentrate reverse the bleeding effects and biomarker changes induced by edoxaban in healthy subjects?

Population

110 healthy subjects in a phase 1 crossover study evaluating the reversal of edoxaban-induced bleeding by 4-factor prothrombin complex concentrate.

Intervention

Intravenous administration of 4-factor prothrombin complex concentrate (4F-PCC) at doses of 50, 25, or 10 IU/kg following administration of edoxaban (60 mg)

Comparator

Placebo following administration of edoxaban (60 mg)

Outcome

Reversal effect on bleeding duration and bleeding volume following punch biopsysurrogate

A 50 IU/kg dose of 4-factor prothrombin complex concentrate completely reverses the bleeding duration and endogenous thrombin potential effects of edoxaban, suggesting its utility for reversing edoxaban anticoagulation.

Cite This Study

Zahir et al. (2014) conducted an RCT in Healthy subjects (n=110). 4-factor prothrombin complex concentrate (4F-PCC) vs. Placebo was evaluated on Bleeding duration and bleeding volume. Intravenous 4F-PCC dose-dependently reversed edoxaban's effects on bleeding duration and endogenous thrombin potential, with complete reversal at 50 IU/kg.

synapsesocial.com/papers/6a786faed8eb58afc2be88f4 https://doi.org/10.1161/circulationaha.114.013445

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Edoxaban Effects on Bleeding Following Punch Biopsy and Reversal by a 4-Factor Prothrombin Complex Concentrate

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Cite This Study

Edoxaban Effects on Bleeding Following Punch Biopsy and Reversal by a 4-Factor Prothrombin Complex Concentrate

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Cite This Study

Also Consider

Also Consider