THÉSÉE

Tinzaparine ou HEparine Standard: Evaluations dans l’Embolie pulmonaire
(1997)

Condition

Initial treatment of acute symptomatic PE

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Objective

To compare the efficacy and safety of fixed-dose tinzaparin compared with adjusted-dose UFH in patients with acute symptomatic PE

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Trial design

Randomized, open study with parallel groups
Active treatment: tinzaparin 175 anti-factor Xa/kg s.c. once daily for at least 5 days and until the concomitant oral anticoagulant therapy resulted in an INR ≥2 (n=304)
Control treatment: UFH 50 IU/kg i.v. bolus followed by 500 IU/kg/day continuous i.v. infusion (target aPTT 2–3 times the control value) for at least 5 days and until the oral anticoagulant therapy induced an INR ≥2.0 (n=308)

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Endpoints

Primary endpoint: composite of recurrent thromboembolism, major bleeding, and death within the first 8 days and at day 90
Secondary endpoint: change from day 1 to day 8 in the extent of scintigraphically detectable pulmonary vascular obstruction

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Trial participants

612 consecutive patients (mean age 67 years) with documented acute symptomatic PE who did not require thrombolytic therapy or embolectomy

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Results

Efficacy outcome: At 8 days, the incidence of the primary endpoint (death, symptomatic recurrent thromboembolism or major bleeding) was similar in the tinzaparin and UFH group (3.0% vs. 2.9%). By day 90, this incidence was slightly, but not significantly, lower in patients assigned to tinzaparin than in patients assigned to UFH (5.9% vs. 7.1%). From day 1 to day 8, 4 of 304 patients (1.3%) receiving tinzaparin died, as compared with 3 of 308 patients (1.0%) receiving UFH. The mortality rates at 3 months were 3.9% and 4.5%, respectively. At day 8, the absolute decrease in pulmonary vascular obstruction was 18.4±13.5% in 258 patients assigned to tinzaparin and 19.0±13.9% in 260 patients assigned to UFH
Safety outcome: At day 8, 1.0% in the tinzaparin group and 1.6% in the UFH group had episodes of major bleeding. By 3 months the incidences were 2.0% and 2.6%, respectively. During the initial treatment, minor bleeding was noted in 17 patients receiving tinzaparin and 8 patients receiving UFH (p=0.10)

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Summary

Efficacy: Treatment of confirmed PE with fixed-dose tinzaparin was as effective as treatment with adjusted-dose UFH
Safety: The incidence of major bleeding was similar with tinzaparin and UFH throughout the study

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Reference

Simonneau G, Sors H, Charbonnier B, Page Y, Laaban J-P, Azarian R, Laurent M, Hirsch J-L, Ferrari E, Bosson J-L, Mottier D, Beau B, for the THÉSÉE Study Group. A comparison of low-molecular weight heparin with unfractionated heparin for acute pulmonary embolism. N Engl J Med 1997;337:663-669

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Corresponding author

Gérald Simonneau, MD, Service de Pneumologie et Réanimation, Hôpital Antoine Béclère, 157 rue de la Porte de Trivaux, 92141 Clamart, France

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