What is the clinical evidence from this study?

Study design: RCT. Population: clopidogrel-induced bleeding (n=40). Intervention: Recombinant activated FVII (rFVIIa) vs. placebo. Primary outcome: bleed duration [BD].

What question did this study set out to answer?

To evaluate the safety and efficacy of recombinant activated factor VII (rFVIIa) in reversing clopidogrel-induced bleeding in healthy participants.

October 1, 2011Anesthesia & Analgesia

Reversal of Clopidogrel-Induced Bleeding with rFVIIa in Healthy Subjects

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Key result

Recombinant FVIIa (10 and 20 μg/kg) significantly mitigated clopidogrel-induced blood loss volume (P=0.007 and P=0.001) and reduced bleed duration in a subgroup analysis (P=0.048).

Why the study?

Does recombinant activated FVII (rFVIIa) reduce bleed duration in healthy subjects with clopidogrel-induced bleeding?

Population

40 healthy subjects with experimentally induced punch biopsy after clopidogrel treatment.

Comparison

Recombinant activated FVII 10 and 20 μg/kg vs Placebo

Design

RCT, randomized, double-blind, placebo-controlled

Authors

BSBrett E. SkolnickThe Royal Melbourne Hospital MSMagdy ShenoudaNovartis (Switzerland)NKNaum KhutoryanskyDrexel University

Discussion

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Implication

rFVIIa may reverse clopidogrel effects experimentally; extends healthy-volunteer data but leaves open patient efficacy and safety.

Key Points

To evaluate the safety and efficacy of recombinant activated factor VII (rFVIIa) in reversing clopidogrel-induced bleeding in healthy participants.
Single-center, randomized, placebo-controlled, double-blind, dose-escalation phase I trial in healthy subjects receiving clopidogrel.
Bleeding was experimentally induced via punch biopsy to measure bleed duration, blood loss volume, and thromboelastography parameters across escalating doses of rFVIIa or placebo.
Of 40 randomized subjects, 56% were discontinued due to low clopidogrel responsiveness (≤30% platelet aggregation inhibition), leaving 37 participants evaluable for efficacy.
Recombinant FVIIa significantly reduced clopidogrel-enhanced blood loss volume at doses of 10 μg/kg (P = 0.007) and 20 μg/kg (P = 0.001) relative to baseline.
In a subgroup of subjects biopsied by the same physician, 20 μg/kg rFVIIa significantly decreased bleed duration compared to clopidogrel alone (P = 0.048).
Ex vivo thromboelastography revealed accelerated clotting dynamics, showing significant improvements in clot onset time and clot angle (P < 0.005).

Study Design

Type

RCT (n=40)

Blinding

double-blind

Randomization

randomized

Multicenter

Structured PICO

Does recombinant activated FVII (rFVIIa) reduce bleed duration in healthy subjects with clopidogrel-induced bleeding?

Population

40 healthy subjects evaluated for reversal of clopidogrel-enhanced bleeding in an experimentally induced punch biopsy.

Intervention

Recombinant activated FVII (rFVIIa) 10 and 20 μg/kg

Comparator

Placebo

Outcome

Bleed duration (BD) induced by punch biopsysurrogate

In a phase I trial of healthy subjects, rFVIIa at 10 and 20 μg/kg successfully reversed clopidogrel-induced blood loss from experimental punch biopsies.

Limitations

Early trial termination limited the evaluation of effects of higher rFVIIa doses.
A significant number of subjects (56%) had limited response to clopidogrel and were discontinued from study.
Early trial termination limited the evaluation of effects of higher rFVIIa doses
Significant number of subjects (56%) had limited response to clopidogrel and were discontinued

Cite This Study

Skolnick et al. (2011) conducted an RCT in clopidogrel-induced bleeding (n=40). Recombinant activated FVII (rFVIIa) vs. placebo was evaluated on bleed duration [BD]. Recombinant FVIIa (10 and 20 μg/kg) significantly mitigated clopidogrel-induced blood loss volume (P=0.007 and P=0.001) and reduced bleed duration in a subgroup analysis (P=0.048).

synapsesocial.com/papers/6a86e4d84a47ef1dc7d3b9d3 https://doi.org/10.1213/ane.0b013e318228c690

Topics

Dual antiplatelet therapy

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Reversal of Clopidogrel-Induced Bleeding with rFVIIa in Healthy Subjects

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Limitations

Cite This Study

Topics

Reversal of Clopidogrel-Induced Bleeding with rFVIIa in Healthy Subjects

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Limitations

Cite This Study

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Topics

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