ENOXAPARIN Clinical Trial Group (3)

Enoxaparin once or twice daily vs. intravenous unfractionated heparin for VTE treatment (2001)

Condition

Treatment of acute VTE

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Objective

To determine whether subcutaneous enoxaparin administered once or twice daily is as effective as continuously infused unfractionated heparin in acute symptomatic VTE

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Trial design

Randomized, partially blinded (dosing of enoxaparin) equivalence study with parallel groups
Active treatment: enoxaparin 1 mg/kg s.c. twice daily (n= 312) or 1.5 mg/kg once daily (n= 298) for ≥5 days and until the concomitant oral anticoagulant therapy resulted in an INR 2.0–3.0
Control treatment: UFH, initial i.v. bolus followed by continuous infusion to target an aPTT of 55–80 s, for ≥5 days until INR 2.0–3.0 (n=290)

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Endpoints

Primary efficacy endpoint: symptomatic recurrent DVT or PE during 3-month follow-up
Primary safety endpoints: major and minor bleeding, any adverse safety events
Secondary endpoints: subgroup analyses according to demographic and physical characteristics, risk factors for and location of VTE

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Trial participants

900 patients (mean age 60.7 years) with symptomatic lower-extremity DVT, including 287 (32%) with confirmed PE; of these 900 patients, 740 were evaluable

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Results

Efficacy outcome: Among all treated patients (n=900), VTE recurred in 12 of 290 (4.1%) patients in the UHF group, 9 of 312 (2.9%) in the twice-daily enoxaparin group, and 13 of 298 patients (4.4%) in the once-daily enoxaparin group. Both enoxaparin treatments met preestablished criteria for efficacy equivalent to that of UFH. The findings for the evaluable patients (n=740) also met the protocol-specified definition for treatment equivalence. Patients with cancer and symptomatic pulmonary embolism were more likely to develop recurrence regardless of treatment group
Safety outcome: Major hemorrhage occurred in 6 of 290 (2.1%) patients assigned to UFH, 4 of 312 (1.3%) patients receiving twice-daily enoxaparin, and 5 of 298 patients (1.7%) receiving once-daily enoxaparin. 9 patients in the UFH group (3.1%), 7 in the twice-daily enoxaparin group (2.2%), and 11 in the once-daily enoxaparin group (3.7%) died during 3-month follow-up. The incidence of thrombocytopenia was similar in the 3 treatment groups

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Summary

Efficacy: Enoxaparin administered subcutaneously once or twice daily was as effective as UFH in preventing recurrence of venous thromboembolic disease. The protocol-specified definition of equivalence was achieved by both enoxaparin regimens for all treated patients and evaluable patients
Safety: The treatment groups did not differ significantly in safety profile

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Reference

Merli G, Spiro TE, Olsson CG, Abildgaard U, Davidson BL, Eldor A, Elias D, Grigg A, Musset D, Rodgers GM, Trowbridge AA, Yusen RD, Zawilska K, for the Enoxaparin Clinical Trial Group. Subcutaneous enoxaparin once or twice daily compared with intravenous unfractionated heparin for treatment of venous thromboembolic disease. Ann Intern Med 2001;134:191-202

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Corresponding author

Theodore E. Spiro, MD, Aventis Pharma SA, Cardiovascular Therapeutic Area, 20 Avenue Raymond Aron, 92165 Antony Cedex, France, e-mail: theodore.spiro@aventis.com

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