title: Efficacy and safety of protein C concentrate to treat purpura fulminans and thromboembolic events in severe congenital protein C deficiency.
abstract: Severe congenital protein C (PC) deficiency (SCPCD) is associated with disseminated intravascular coagulation (DIC), purpura fulminans (PF), and vascular thromboembolic events (TE), often leading to organ failure and death. PC replacement therapy offers a safe, effective treatment for thromboembolic complications of SCPCD and secondary prophylaxis for recurrent DIC, PF, and TEs. A prospective, multi-centre, open-label, phase 2/3 study was conducted to demonstrate the safety and efficacy of protein C concentrate for treatment of PF and acute TEs. Fifteen enrolled patients with SCPCD received protein C concentrate; 11 received treatment for acute TEs (PF, 18 events; PF and other coumarin-related vascular thromboembolic events [coumarin-induced skin necrosis; CISN], 1 event; venous thrombosis, 5 events). Pre-defined efficacy criteria for treatment of acute TEs were compared with a historical control arm (i. e. patients receiving conventional therapy without protein C replacement). PF/CISN was demonstrated by pre-defined primary and secondary efficacy ratings. Primary ratings of protein C concentrate-treated episodes were significantly higher (p=0.0032) than in the historical control. For 19 PF/CISN episodes in 11 patients, 94.7 % of treatments were rated effective and 5.3 % effective with complications (not related to protein C concentrate). In a secondary efficacy rating, all treatments were rated effective (68.4 % excellent; 21.1 % good; 10.5 % fair). For 5/24 vascular thrombosis episodes, 80 % of treatments were rated excellent and 20 % were rated good. No treatment-related adverse events or serious adverse events occurred. In conclusion, protein C concentrate provides an efficacious, safe treatment for PF, CISN, and other TEs in SCPCD patients.
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Manco-Johnson
authors.forename: Lisa
authors.initials: L
authors.lastname: Bomgaars
authors.forename: Joseph
authors.initials: J
authors.lastname: Palascak
authors.forename: Amy
authors.initials: A
authors.lastname: Shapiro
authors.forename: John
authors.initials: J
authors.lastname: Geil
authors.forename: Sandor
authors.initials: S
authors.lastname: Fritsch
authors.forename: Borislava G
authors.initials: BG
authors.lastname: Pavlova
authors.affiliation: David Gelmont, BioTherapeutics Clinical Research, Baxalta US Inc., One Baxter Way, Westlake Village, CA 91362-3811, USA, Tel.: +1 805 372 3352, Fax: +1 805 372 3492, E-mail: david.gelmont@baxalta.com.
authors.forename: David
authors.initials: D
authors.lastname: Gelmont
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011446:Prospective Studies; D011486:Protein C / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020151:Protein C Deficiency / Q000150:complications / Q000151:congenital / Q000188:drug therapy*; D055665:Purpura Fulminans / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D055502:Secondary Prevention; D013923:Thromboembolism / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D011486:Protein C
keywords: Disseminated intravascular coagulation; congenital thrombotic disease due to protein C deficiency; protein C deficiency; purpura fulminans; therapeutics