Evidence & regulatory context
- Mechanism
- Coagulation factor VIII inhibitor (INHIBITOR); Coagulation factor V inhibitor (INHIBITOR)
- Target
- CHEMBL3143; CHEMBL3618
- Injury models
- Spinal cord injury · Ischaemia-reperfusion
- Reported indication
- Drotrecogin alfa (activated) (Xigris) - recombinant activated protein C, approved 2001 for reduction of mortality in adults with severe sepsis at high risk of death (APACHE II >=25)
- First approval
- 2001
- Development stage
- Approved 2001 for severe sepsis then withdrawn worldwide 2011 (PROWESS-SHOCK no benefit)
- ChEMBL max phase
- 4 / 4 (development scale, not regulatory approval)
- Synonyms
- Activated protein c; Drotrecogin alfa; Drotrecogin alfa (activated); LY-203638; Xigris
- Note
- Not recorded
Clinical trials 8
0 linked trials carry an injury-indication flag. These flags support record-level exploration and sit alongside the stringent aggregate counts described in Methods.
An Evaluation of Vasopressor Requirement, Hemodynamic Response and Measures of Tissue Perfusion With the Administration of Drotrecogin Alfa (Activated) as Part of Physician-Directed Therapy in Patients With Septic Shock
Sepsis · Septic Shock
Enrolment: 43 · Results not recorded
A Safety Evaluation of Xigris Drotrecogin Alfa Activated in Hematopoietic Stem Cell Transplant Patients With Severe Sepsis
Sepsis · Hematologic Neoplasms · Hematopoietic Stem Cell Transplantation · Infection
Enrolment: 7 · Results not recorded
Modulation of Vasoreactivity in Septic Shock: Impact of Recombinant Protein C
Septic Shock
Enrolment: 30 · Results not recorded
A Randomized, Double-Blind, Placebo-Controlled Trial of Prophylactic Heparin in Patients With Severe Sepsis and Higher Disease Severity Who Are Undergoing Treatment With Drotrecogin Alfa (Activated)
Sepsis
Enrolment: 2000 · Results not recorded
A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 3 Study of Drotrecogin Alfa (Activated) Administered as a Continuous 96-hr Infusion to Adult Patients With Septic Shock
Sepsis
Enrolment: 1696 · Results not recorded
A Phase IIIb Study to Determine Efficacy and Safety of Extended Drotrecogin Alfa (Activated) Therapy in Patients With Persistent Requirement for Vasopressor Support After 96 Hour Infusion With Commercial Drotrecogin Alfa (Activated)
Sepsis · Hypotension
Enrolment: 200 · Results not recorded
Activated Protein C in Acute Stroke Trial
Stroke
Enrolment: 12 · Results not recorded
Imaging Biomarkers of Pulmonary Inflammation
Lung Inflammation
Enrolment: 22 · Results not recorded
Preclinical evidence 2
2 studies reported at therapy level; 2 evidence entries itemised.
MouseSpinal cord injuryContusionPAR-1 null on a C57BL/6 background, and wild-type C57BL/6Malen = Total n = 100 adult male mice; n = 28 for neutrophil quanti…Intravenous bolus of 0.3 mL followed immediately by a 0.3 mL subcutaneous dose2 mg/kg body weight in saline20 min after injury
Model: Moderate contusive spinal cord injury at mid-thoracic level, laminectomy at T8 with a 3 g weight dropped 5 cm onto the impactor tip
Recombinant activated protein C given 20 min after contusion improved locomotor recovery in wild-type mice from 14 days post-injury but gave no additional benefit in PAR-1 null mice, indicating a PAR-1 dependent effect. PAR-1 null mice showed less neutrophil infiltration, better barrier integrity,…
Extraction: extract · Subtype source: rule · Supplied extraction confidence: 0.93. Machine-extracted fields require source verification.
MouseIschaemia-reperfusionRenalC57BL/6jMaleIntraperitoneal200 micrograms/kg APC or mutant APC; blocking monoclonal an…
Model: Renal ischaemia and reperfusion injury
APC reduced tubular injury and improved renal function without altering inflammation, and the mutant lacking anticoagulant activity was equally protective, indicating the benefit is independent of anticoagulation.
Extraction: extract · Subtype source: rule · Supplied extraction confidence: 0.75. Machine-extracted fields require source verification.
