UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Efficacy of recombinant human soluble thrombomodulin for disseminated intravascular coagulation (DIC) occurred in patients with severe sepsis
Title of the study (Brief title)	Efficacy of recombinant thrombomodulin for patients with severe sepsis
Region	Japan

Condition
Condition	Severe sepsis with disseminated intravascular coagulation (DIC)
Classification by specialty	Medicine in general Infectious disease Emergency medicine Intensive care medicine
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	The purpose of this study was to show that administration of recombinant human soluble thrombomodulin can increase the survival rate after the 28 hospital days and 3 month, and improve organ dysfunctions including coagulation systems for patients with severe sepsis or septic shock who fulfilled the diagnosis criteria of acute DIC and were diagnosed DIC.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Explanatory
Developmental phase	Not applicable

Assessment
Primary outcomes	the survival rate after the 28 hospital days and 3 month.
Key secondary outcomes	1. SOFA score, MODS score 2. CRP value, platelet value, FDP value, D-dimer value 3. Duration of administration of catecholamine 4. Total fluid value until stopping administration of catecholamine 5. The volume of blood transfusion until 72 hours and the total volume until the discharge (RBC volume, FFP volume, platelet volume) 6. Duration of mechanical ventilation 7. The survival rate of 72 hours

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification	YES
Dynamic allocation	NO
Institution consideration	Institution is not considered as adjustment factor.
Blocking	NO
Concealment	Numbered container method

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	The rhTM group When the patients with severe sepsis are diagnosed DIC (the acute DIC), they are injected intravenously with recombinant human soluble thrombomodulin (rhTM) within 24 hrs after the diagnosis.
Interventions/Control_2	The attending physician performed the standard treatment according to "Surviving sepsis campaign 2008"on the patients in both the rhTM group and the control group.
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	16 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1) The patients with severe sepsis or septic shock admitted to the National Center For Global Health and Medicine, Japan 2) 1) and the patients were diagnosed DIC using the acute DIC criteria within 24 hrs after the admission.
Key exclusion criteria	1. The patients who have the need for the emergency surgery. 2. The patients and/or their family who refuse the intensive care (intratracheal intubation, mechanical ventilation, administration of catecholamine, etc.). 3. The patients who have intracranial bleeding, pulmonary hemorrhage, gastrointestinal hemorrhage (persistent hematemesis, persistent hemorrhagic stool or persistent bleeding from gastrointestinal ulcer). 4. The patients who have fulminant hepatic failure, decompensated cirrhosis, or other sever hepatic diseases. 5. The patients who have allergies to rhTM 6. The pregnant women, or the patients who have the possibility of pregnancy.
Target sample size	100

Research contact person
Name of lead principal investigator	Akiyoshi Hagiwara
Organization	National Center For Global Health and Medicine, Japan
Division name	Emergency Medicine and Critical Care
Address	1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
TEL	03-3202-7181
Email	ahagiwar@hosp.ncgm.go.jp

Public contact
Name of contact person	Akiyoshi Hagiwara
Organization	National Center For Global Health and Medicine, Japan
Division name	Emergency Medicine and Critical Care
Address	1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
TEL	03-3202-7181
Homepage URL
Email	ahagiwar@hosp.ncgm.go.jp

Sponsor
Institute	The ethics committees of National Center For Global Health and Medicine, Japan
Institute
Department

Funding Source
Organization	none
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2012 Year 08 Month 01 Day

Progress
Recruitment status	Main results already published
Date of protocol fixation	2012 Year 06 Month 21 Day
Anticipated trial start date	2012 Year 08 Month 01 Day
Last follow-up date	2015 Year 05 Month 31 Day
Date of closure to data entry	2015 Year 05 Month 31 Day
Date trial data considered complete	2015 Year 10 Month 30 Day
Date analysis concluded	2016 Year 10 Month 31 Day

Related information
URL releasing protocol
Publication of results	Published
URL releasing results	http://bmjopen.bmj.com/content/6/12/e012850.full?sid=92554706-82b6-4e0e-bd98-7027abc37a94
Results	The 28-day survival rates were 84% and 83% in the control and rhTM groups, respectively (p=0.745, log-rank test). The 90-day survival rates were 73% and 72% in the control and rhTM groups, respectively (p=0.94, log-rank test). Meanwhile, the rates of recovery from DIC (<4) were significantly higher in the rhTM group than in the control group (p=0.001, log-rank test). Relative change from baseline of d-dimer levels was significantly lower in the rhTM group than in the control group, on days 3 and 5.
Other related information

Management information
Registered date	2012 Year 07 Month 04 Day
Last modified on	2017 Year 01 Month 03 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009808