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Summary of clinical trials with drotrecogin alfa (activated) in severe sepsis |
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| Study |
Patients (n) |
Study type |
Main findings |
Comments |
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| Adults |
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| Phase II [1] |
131 |
RCT |
Reduction in D-dimer and interleukin-6 plasma levels with DrotAA; reduction in 28-day all-cause mortality (not significant); no difference in bleeding events |
Dose-finding study; optimal dose defined as 24 μg/kg per hour; benefit more pronounced in high-risk patients |
| PROWESS [2] |
1,690 |
RCT |
Significant reduction in 28-day, all-cause mortality; faster resolution of organ dysfunction; consistent survival benefit in more than 70 subgroups; reduced ospital and 3 month mortality |
Increased survival benefit in patients at high risk for death; no benefit in single organ dysfunction and low APACHE II score; increased incidence of serious bleeding events |
| ENHANCE [11] |
2,378 |
Open label |
Similar 28-day, all-cause mortality compared with PROWESS; earlier intervention associated with improved outcome (<24 hours) |
Increased incidence of bleeding events compared with PROWESS |
| ADDRESS [12] |
2,640 |
RCT |
No difference in 28-day and hospital all-cause mortality in patients at low risk for death |
Increased incidence of bleeding events; no increased incidence in ICH |
| XPRESS [13] |
1,994 |
RCT |
Concomitant heparin does not increase 28-day mortality; heparin prophylaxis should not be discontinued before DrotAA |
Small increase in nonserious bleeding; prophylactic heparin reduces incidence of ischaemic stroke |
| Children |
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| Phase Ib [14] |
83 |
Open label |
Safety and pharmacokinetic/pharmacodynamic study; pharmacokinetics/pharmacodynamics similar to adults |
Safety similar to adults |
| RESOLVE [15] |
477 |
RCT |
No difference in time to organ failure resolution; no difference in 28-day mortality; no difference in the incidence of serious bleeding events |
More ICH in children younger than 60 days in DrotAA arm |
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ADDRESS, Administration of Drotrecogin alfa (activated) in early stage Severe Sepsis; APACHE, Acute Physiology and Chronic Health Evaluation; DrotAA, drotecogin alfa (activated); ENHANCE, Extended Evaluation of Recombinant Human Activated Protein C; ICH, intracerebral haemorrhage; PROWESS, Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis; RCT, randomized controlled trial; RESOLVE, REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspective; XPRESS, Xigris and Prophylactic hepaRin Evaluation in Severe Sepsis. | ||||
Laterre Critical Care 2007 11(Suppl 5):S5 doi:10.1186/cc6156 |
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