PURPOSE: The safety of using heparin concomitantly with drotrecogin alfa (activated) {DrotAA} was explored in the XPRESS study. No heparin effect on mortality was observed. Safety results from that study are explored in more detail. METHODS: A randomized, double-blind trial of prophylactic heparin versus placebo in severe sepsis patients treated with DrotAA (24 microg/(kg h) for 96 h) was conducted at 224 sites in 20 countries. Patients were randomized 1:1:2 to receive unfractionated heparin (UFH) (5,000 Units twice daily) (n = 511), low-molecular-weight heparin (LMWH) (enoxaparin, 40 mg per day) (n = 493), or placebo (n = 990) every 12 h during the DrotAA infusion. RESULTS:Bleeding events during the DrotAA infusion period (Days 0-6) were higher in the heparin than placebo groups (10.8 vs. 8.1%; p = 0.049), but serious bleeding events were similar (heparin 2.3% vs. placebo 2.5%; p = 0.72) and central nervous system (CNS) bleeds were rare in both groups (0.3 vs. 0.3%). Fewer heparin patients experienced an ischemic stroke during infusion (0.3 vs. 1.3%; p = 0.018) and 28-day period (0.5 vs. 1.8%; p = 0.009). CONCLUSIONS: Coadministration of DrotAA with low-dose heparin in severe sepsis patients did not increase incidence of serious bleeding. Fewer ischemic strokes in the heparin group suggest heparin cessation should be avoided during DrotAA infusion.
RCT Entities:
PURPOSE: The safety of using heparin concomitantly with drotrecogin alfa (activated) {DrotAA} was explored in the XPRESS study. No heparin effect on mortality was observed. Safety results from that study are explored in more detail. METHODS: A randomized, double-blind trial of prophylactic heparin versus placebo in severe sepsispatients treated with DrotAA (24 microg/(kg h) for 96 h) was conducted at 224 sites in 20 countries. Patients were randomized 1:1:2 to receive unfractionated heparin (UFH) (5,000 Units twice daily) (n = 511), low-molecular-weight heparin (LMWH) (enoxaparin, 40 mg per day) (n = 493), or placebo (n = 990) every 12 h during the DrotAA infusion. RESULTS:Bleeding events during the DrotAA infusion period (Days 0-6) were higher in the heparin than placebo groups (10.8 vs. 8.1%; p = 0.049), but serious bleeding events were similar (heparin 2.3% vs. placebo 2.5%; p = 0.72) and central nervous system (CNS) bleeds were rare in both groups (0.3 vs. 0.3%). Fewer heparinpatients experienced an ischemic stroke during infusion (0.3 vs. 1.3%; p = 0.018) and 28-day period (0.5 vs. 1.8%; p = 0.009). CONCLUSIONS: Coadministration of DrotAA with low-dose heparin in severe sepsispatients did not increase incidence of serious bleeding. Fewer ischemic strokes in the heparin group suggest heparin cessation should be avoided during DrotAA infusion.
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