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A Multicenter, Randomized, Placebo-Controlled, Double-blind Study

Bengt I. Eriksson, MD, PhD; Michael R. Lassen, MD; for the PENTasaccharide in HIp-FRActure Surgery Plus (PENTHIFRA Plus) Investigators

Arch Intern Med. 2003;163:1337-1342.

Background  The benefit of thromboprophylaxis for 1 month has never been evaluated in patients undergoing hip fracture surgery, a setting in the highest risk category for postoperative venous thromboembolism (VTE).

Methods  In a double-blind multicenter trial, 656 patients undergoing hip fracture surgery were randomly assigned to receive prophylaxis with a once-daily subcutaneous injection of either 2.5 mg of fondaparinux sodium or placebo for 19 to 23 days. Before randomization, all patients had received fondaparinux for 6 to 8 days. The primary efficacy outcome was VTE occurring during the double-blind period (deep vein thrombosis detected by mandatory bilateral venography or documented symptomatic deep vein thrombosis or pulmonary embolism). The main safety outcome was major bleeding.

Results  The primary efficacy outcome was assessed in 428 patients. Fondaparinux reduced the incidence of VTE compared with placebo from 35.0% (77/220) to 1.4% (3/208), with a relative reduction in risk of 95.9% (95% confidence interval, 87.2%-99.7%; P<.001). Similarly, the incidence of symptomatic VTE was significantly lower with fondaparinux (1/326; 0.3%) than with placebo (9/330; 2.7%). The relative reduction in risk was 88.8% (P = .02). Although there was a trend toward more major bleeding in the fondaparinux group than in the placebo group (P = .06), there were no differences between the 2 groups in the incidence of clinically relevant bleeding (leading to death, reoperation, or critical organ bleeding).

Conclusions  Extended prophylaxis with fondaparinux for 3 weeks after hip fracture surgery reduced the risk of VTE by 96% and was well tolerated.

From Orthopedics Departments, Sahlgrenska University Hospital/Östra, Göteborg, Sweden (Dr Eriksson), and University Hospital of Copenhagen Hillerød, Hillerød, Denmark (Dr Lassen). Drs Eriksson and Lassen have served as consultants to Sanofi-Synthelabo and NV Organon.

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