VAN GOGH

Idraparinux versus standard therapy for venous thromboembolic disease (2007)

Condition

Treatment of DVT and acute PE

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Objective

To demonstrate that idraparinux is at least as effective and safe as standard therapy (low molecular weight heparin or heparin, followed by an adjusteddose vitamin K antagonist) in the treatment of patients with DVT or PE

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Trial design

Two separate, randomized, open-label, non-inferiority phase III trials with parallel groups

DTV study
Active treatment: idraparinux 2.5 mg s.c. once weekly for either 3 or 6 months (n=321 in the 3-month stratum; n=1131 in the 6-month stratum)
Control treatment: tinzaparin, enoxaparin, or i.v. heparin adjusted for an activated partial-thromboplastin time of 1.5–2.5, followed by adjusted-dose warfarin or acenocoumarol (target INR 2.0–3.0) for either 3 or 6 months (n=316 in the 3-month stratum; n=1136 in the 6-month stratum)

PE Study
Active treatment: idraparinux 2.5 mg s.c. once weekly for either 3 or 6 months (n=102 in the 3-month stratum; n=103 in the 6-month stratum)
Control treatment: standard therapy as in the DVT study (n=993 in the 3-month stratum; n=1017 in the 6-month stratum)

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Endpoints

Primary efficacy endpoint: incidence of symptomatic recurrent VTE (nonfatal or fatal)
Primary safety endpoints: clinically relevant bleeding (major or non-major) and death from all causes

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Trial participants

DVT Study: 2904 patients aged ≥18 years (mean 58 years) with acute symptomatic VTE (lower-extremity symptoms)
PE Study: 2215 patients aged ≥18 years (mean 62 years) with acute symptomatic VTE (chest symptoms)

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Results

DVT Study
Efficacy outcome: At 3 months, the incidence of recurrent VTE was 2.9% in the idraparinux group as compared with 3.0% in the standard-therapy group (odds ratio 0.98; p<0.001 for non-inferiority). The rates in the 6-month stratum were similar in both groups (3.7% and 3.7%, respectively)
Safety outcome: At 3 months, clinically relevant bleeding had occured in 4.5% of the patients treated with idraparinux and 7.0% in the standardtherapy group (p=0.004). In the 6-month stratum, the incidence was 8.3% in the idraparinux arm and 8.1% in patients receiving standard therapy (p=0.85). The corresponding rates of major bleeding were 0.8% and 1.2%, respectively, at 3 months (p=0.35) and 1.9% and 1.5% at 6 months (p=0.50). At 3 months, the mortality was 2.3% in the idraparinux group and 2.0% in the standard-therapy group (p= 0.61). In the 6-month stratum the mortality rates were 4.9% and 3.9%, respectively (p=0.25)

PE Study
Efficacy outcome: In the 3-month stratum, the incidence of recurrent VTE was 3.4% in patients treated with idraparinux and 1.6% in patients assigned to standard therapy (odds ratio 2.14; p=0.59 for non-inferiority). The corresponding rates in the 6-month stratum were 4.0% and 2.0%, respectively
Safety outcome: The incidence of clinically relevant bleeding at 3 months was 5.8% in the idraparinux group and 8.2% in the standard-therapy group. These rates in the 6-month stratum were 7.7% and 9.7%, respectively. The corresponding rates of major bleeding were 1.1% and 2.1% at 3 months and 1.4% and 2.8% at 6 months. At 3 months, the rate of all-cause death was 5.1% in the idraparinux group and 2.9% in the standard-therapy group (p=0.006). In the 6-month stratum the mortality rates were 6.4% and 4.4%, respectively (p=0.04)

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Summary

Efficacy: In patients with DVT, the efficacy of once-weekly subcutaneous idraparinux in preventing subsequent thromboembolic events was similar to that of standard therapy with heparin plus vitamin K antagonist. In contrast, in patients with PE, the efficacy of idraparinux was inferior to that of standard therapy
Safety: Bleeding rates in the idraparinux groups were similar to or lower than those in the standard-therapy groups. However, there was an excess of early fatal and non-fatal recurrences of PE. In patients with PE, the idraparinux treatment was associated with an increase in total mortality

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Reference

The van Gogh Investigators; Büller HR, Cohen AT, Davidson B, Decousus H, Gallus AS, Gent M, Pillion G, Piovella F, Prins MH, Raskob GE. Idraparinux versus standard therapy for venous thromboembolic disease. N Engl J Med 2007;357:1094-1104

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Corresponding author

Prof. Harry R. Büller, Department of Vascular Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands
e-mail:h.r.buller@amc.uva.nl

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