Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial.

Abstract

BACKGROUND:

Soluble thrombomodulin is a promising therapeutic natural anticoagulant that is comparable to antithrombin, tissue factor pathway inhibitor and activated protein C.

OBJECTIVES:

We conducted a multicenter, double-blind, randomized, parallel-group trial to compare the efficacy and safety of recombinant human soluble thrombomodulin (ART-123) to those of low-dose heparin for the treatment of disseminated intravascular coagulation (DIC) associated with hematologic malignancy or infection.

METHODS:

DIC patients (n = 234) were assigned to receive ART-123 (0.06 mg kg(-1) for 30 min, once daily) or heparin sodium (8 U kg(-1) h(-1) for 24 h) for 6 days, using a double-dummy method. The primary efficacy endpoint was DIC resolution rate. The secondary endpoints included clinical course of bleeding symptoms and mortality rate at 28 days.

RESULTS:

DIC was resolved in 66.1% of the ART-123 group, as compared with 49.9% of the heparin group [difference 16.2%; 95% confidence interval (CI) 3.3-29.1]. Patients in the ART-123 group also showed more marked improvement in clinical course of bleeding symptoms (P = 0.0271). The incidence of bleeding-related adverse events up to 7 days after the start of infusion was lower in the ART-123 group than in the heparin group (43.1% vs. 56.5%, P = 0.0487).

CONCLUSIONS:

When compared with heparin therapy, ART-123 therapy more significantly improves DIC and alleviates bleeding symptoms in DIC patients.

• Authors: H Saito, I Maruyama, S Shimazaki, Y Yamamoto, N Aikawa, R Ohno, A Hirayama, T Matsuda, H Asakura, M Nakashima, N Aoki
• Journal: Journal of thrombosis and haemostasis : JTH (J Thromb Haemost) Vol. 5 Issue 1 Pg. 31-41 (Jan 2007) ISSN: 1538-7933 [Print] England
• PMID: 17059423 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• ART123
• Anticoagulants
• Recombinant Proteins
• Thrombomodulin
• Heparin

Topics

• Aged
• Anticoagulants (administration & dosage, adverse effects, therapeutic use)
• Blood Coagulation (drug effects)
• Blood Coagulation Tests
• Disseminated Intravascular Coagulation (blood, drug therapy, mortality)
• Double-Blind Method
• Drug Administration Schedule
• Female
• Heparin (therapeutic use)
• Humans
• Male
• Middle Aged
• Prospective Studies
• Recombinant Proteins (administration & dosage, adverse effects, therapeutic use)
• Thrombomodulin (administration & dosage, therapeutic use)
• Treatment Outcome