November 16, 2012Blood

Reversal of Dabigatran's Anticoagulant Activity in the Monkey by a Specific Antidote and Pharmacokinetic and Pharmacodynamic Modeling

Q: What is the clinical evidence from this study?

Study design: Other. Population: Anticoagulant reversal (n=6). Intervention: Dabigatran-specific antidote (humanized Fab) vs. Control / Dabigatran alone. Primary outcome: Reversal of dabigatran's anticoagulant activity.

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Key result

A dabigatran-specific antidote successfully reversed the anticoagulant activity of dabigatran in rhesus monkeys in a dose-dependent manner.

Why the study?

Does a specific humanized Fab antidote reverse the anticoagulant activity of dabigatran in Rhesus monkeys?

Population

Rhesus monkeys (n=2/group, total n=6)

Comparison

Dabigatran etexilate 12 mg/kg/day orally on Days… vs Control (vehicle) and antidote alone groups

Design

Preclinical

Follow-up

32 days

Authors

JTJoshuaine G. TothBoehringer Ingelheim (United States)GGGuanfa GanBoehringer Ingelheim (Brazil)JRJoanne van RynCross-Cutting Cardiology

Discussion

Member takes

Implication

Supports antidote development for human trials; leaves open clinical translation and efficacy.

Structured PICO

Does a specific humanized Fab antidote reverse the anticoagulant activity of dabigatran in Rhesus monkeys?

Population

6 rhesus monkeys receiving dabigatran etexilate and/or a specific antidote to evaluate pharmacokinetics and pharmacodynamics.

Intervention

Dabigatran etexilate 12 mg/kg/day orally on Days 1-4, 15-18, and 29-32 plus a single IV dose of a specific humanized Fab antidote (30, 90, or 175 mg/kg) administered 90 minutes after dabigatran on Days 4, 18, and 32

Comparator

Control (vehicle) and antidote alone groups

Outcome

Pharmacokinetics and pharmacodynamics (coagulation activity measured by diluted thrombin time assay) of dabigatran and its antidotesurrogate

A specific humanized Fab antidote rapidly and completely reversed the anticoagulant activity of dabigatran in a monkey model, with a combined PK/PD model accurately describing the data to guide future clinical trials.

Cite This Study

Toth et al. (2012) studied Anticoagulant reversal (n=6). Dabigatran-specific antidote (humanized Fab) vs. Control / Dabigatran alone was evaluated on Reversal of dabigatran's anticoagulant activity. A dabigatran-specific antidote successfully reversed the anticoagulant activity of dabigatran in rhesus monkeys in a dose-dependent manner.

synapsesocial.com/papers/6a9fbb0eead5075722d4bbe2 https://doi.org/10.1182/blood.v120.21.22.22

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Reversal of Dabigatran's Anticoagulant Activity in the Monkey by a Specific Antidote and Pharmacokinetic and Pharmacodynamic Modeling

Discussion

Member takes

Implication

Structured PICO

Cite This Study

Reversal of Dabigatran's Anticoagulant Activity in the Monkey by a Specific Antidote and Pharmacokinetic and Pharmacodynamic Modeling

Discussion

Member takes

Implication

Structured PICO

Cite This Study

Also Consider

Also Consider