ABOUT Recomodulin(ART-123)
  • History of Recomodulin
  • Mechanism of Action
  • The results of the Japanese Phase III clinical study
  • Press release

Japanese Phase III clinical study (double-blind comparative study)

Subjects Patients diagnosed with DIC in accordance with the DIC diagnostic criteria established by the Ministry of Health, Labor and Welfare (underlying diseases are hematologic malignancy or infections).
Dosage and administration
Recomodulin(ART-123) group : 380U/kg (0.06mg/kg), continuous intravenous administration for 30 minutes, once a day
Heparin group : 8 U/kg/hr, continuous intravenous administration for 24 hours
Double-dummy method
Administration period 6 days
Primary endpoint Resolution of DIC (non-inferiority analysis)
Secondary endpoints Clinical course of bleeding symptoms, mortality, normalization of coagulation test values
Evaluation/observation period
7 days after the start of administration : Resolution of DIC, clinical course of bleeding symptoms, and normalization of coagulation test values
14 days after the start of administration : adverse events
28 days after the start of administration : mortality and serious adverse events
Sample size Total: 232
Number of subjects for analysis Resolution of DIC: 224; clinical course of bleeding symptoms and mortality: 227;
normalization of coagulation test values: 208; safety: 231

Efficacy

1. Primary endpoint

Resolution of DIC

The results of an analysis in patients with DIC associated with hematologic malignancy or infections suggest that Recomodulin(ART-123) is not inferior to heparin in terms of resolving DIC.

2. Secondary endpoints

(1) Clinical course of bleeding symptoms

Disappearance of bleeding symptoms (7 days after start of administration)

The clinical course of bleeding symptoms (7 days after start of administration)

(2) 28-day mortality

(3) Normalization of coagulation test values

Safety

1. Bleeding-related adverse events

Group Incidence (%) P-value for Fisher’s exact test (two-sided)
Recomodulin(ART-123) group(n=116) 50(43.1%) 0.0487
Heparin group(n=115) 65(56.5%)

2. Adverse drug reactions

Major adverse drug reactions
  Recomodulin(ART-123) group(n=116) Heparin group(n=115)
Incidence (%) 27 (23.3%)* 29 (25.2%)*
Catheter site hemorrhage 7(6.0%) 7(6.1%)
Elevated serum AST (GOT) 7(6.0%) 4(3.5%)
Elevated serum ALT (GPT) 6(5.2%) 4(3.5%)
Purpura 4(3.4%) 6(5.2%)
Anemia 1(0.9%) 6(5.2%)

*p=0.7605 (Fisher’s exact test)

All adverse drug reactions in a Phase III clinical study

Adverse drug reactions Recomodulin(ART-123) group
(n=116)
Heparin group
(n=115)
Number of subjects (%) Number of subjects (%)
Hemorrhagic disorders Hematuria 3 2.6 4 3.5
Oral hemorrhage 4 3.4 3 2.6
Respiratory tract hemorrhage - - 1 0.9
Purpura 4 3.4 6 5.2
Cerebral hemorrhage - - 1 0.9
Pulmonary hemorrhage 1 0.9 - -
Epistaxis 1 0.9 2 1.7
Melena 1 0.9 1 0.9
Hemorrhage subcutaneous - - 1 0.9
Muscle hemorrhage - - 1 0.9
Hemorrhage intracranial - - 1 0.9
Hematoma 1 0.9 3 2.6
Catheter site hemorrhage 7 6.0 7 6.1
Vessel puncture site hemorrhage 2 1.7 4 3.5
Bone-marrow-aspiration-site hemorrhage - - 1 0.9
Skin and skin appendage disorders Erythematous rash - - 1 0.9
Rash 1 0.9 1 0.9
Central and peripheral nervous system disorders Convulsion - - 2 1.7
Stupor - - 2 1.7
Neuropathy - - 1 0.9
Gastrointestinal system disorders Gastric ulcer 1 0.9 - -
Hiccups - - 1 0.9
Liver and biliary system disorders Abnormal A/G ratio - - 1 0.9
Jaundice 1 0.9 1 0.9
Elevated serum GOT 7 6.0 4 3.5
Elevated serum GPT 6 5.2 4 3.5
Bilirubinemia 1 0.9 1 0.9
Metabolic and nutritional disorders Elevated alkaline phosphatase 1 0.9 5 4.3
Elevated LDH - - 4 3.5
Hypercholesterolemia 1 0.9 - -
Hypokalemia 1 0.9 - -
Hypochloremia 1 0.9 - -
Hypoglycemia - - 1 0.9
Hypocholesterolemia 1 0.9 - -
Hypoproteinemia - - 2 1.7
Hyponatremia - - 1 0.9
Glycosuria 1 0.9 - -
Hypoalbuminemia - - 2 1.7
Decreased cholinesterase 1 0.9 - -
Decreased blood uric acid 1 0.9 - -
Hypertriglyceridemia 2 1.7 2 1.7
Cardiovascular disorders (general) Hypotension - - 1 0.9
Vascular (extracardiac) disorders Vasculitis - - 1 0.9
Thrombosis - - 1 0.9
Cerebrovascular disorder - - 1 0.9
Respiratory system disorders Dyspnea 2 1.7 1 0.9
Red blood cell disorders Anemia 1 0.9 6 5.2
Platelet, bleeding, and clotting disorders Disseminated intravascular coagulation - - 1 0.9
Urinary system disorders Elevated NPN - - 1 0.9
Abnormal renal function . - 1 0.9
Proteinuria 3 2.6 - -
Urinary casts 1 0.9 - -
Elevated BUN - - 1 0.9
Anuria - - 1 0.9
Low urea nitrogen - - 1 0.9
Urinary occult blood positive 4 3.4 1 0.9
Red blood cells in urinary sediment 5 4.3 1 0.9
White blood cells in urinary sediment 1 0.9 - -
Body as a whole - general disorders Chest pain 1 0.9 - -
Pain . - 1 0.9
Pyrexia - - 1 0.9
Edema 1 0.9 - -

Note: These adverse drug reactions are classified in accordance with the Japanese Adverse Drug Reaction Terminology of 1996.