PMID- 19367397
OWN - NLM
STAT- MEDLINE
DCOM- 20091026
LR  - 20211020
IS  - 1432-1238 (Electronic)
IS  - 0342-4642 (Linking)
VI  - 35
IP  - 7
DP  - 2009 Jul
TI  - Comprehensive safety analysis of concomitant drotrecogin alfa (activated) and 
      prophylactic heparin use in patients with severe sepsis.
PG  - 1196-203
LID - 10.1007/s00134-009-1483-7 [doi]
AB  - 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.
FAU - Levy, Mitchell
AU  - Levy M
AD  - Rhode Island Hospital and Brown University Medical School, 593 Eddy St., 
      Providence, RI 02903, USA. mitchell_levy@brown.edu
FAU - Levi, Marcel
AU  - Levi M
FAU - Williams, Mark D
AU  - Williams MD
FAU - Antonelli, Massimo
AU  - Antonelli M
FAU - Wang, Dazhe
AU  - Wang D
FAU - Mignini, Mariano Alejandro
AU  - Mignini MA
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20090415
PL  - United States
TA  - Intensive Care Med
JT  - Intensive care medicine
JID - 7704851
RN  - 0 (Anti-Infective Agents)
RN  - 0 (Anticoagulants)
RN  - 0 (Protein C)
RN  - 0 (Recombinant Proteins)
RN  - 9005-49-6 (Heparin)
RN  - JGH8MYC891 (drotrecogin alfa activated)
SB  - IM
EIN - Intensive Care Med. 2009 Jul;35(7):1322-3
MH  - Anti-Infective Agents/administration & dosage/*therapeutic use
MH  - *Anticoagulants/administration & dosage/adverse effects
MH  - Contraindications
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Female
MH  - Hemorrhage/chemically induced
MH  - *Heparin/administration & dosage/adverse effects
MH  - Humans
MH  - Male
MH  - Protein C/administration & dosage/*therapeutic use
MH  - Recombinant Proteins/administration & dosage/therapeutic use
MH  - Sepsis/*drug therapy
MH  - *Severity of Illness Index
EDAT- 2009/04/16 09:00
MHDA- 2009/10/27 06:00
CRDT- 2009/04/16 09:00
PHST- 2008/07/01 00:00 [received]
PHST- 2009/03/27 00:00 [accepted]
PHST- 2009/04/16 09:00 [entrez]
PHST- 2009/04/16 09:00 [pubmed]
PHST- 2009/10/27 06:00 [medline]
AID - 10.1007/s00134-009-1483-7 [doi]
PST - ppublish
SO  - Intensive Care Med. 2009 Jul;35(7):1196-203. doi: 10.1007/s00134-009-1483-7. Epub 
      2009 Apr 15.