Clinical trial NCT02654561: Efficacy and Safety of Unfractionated Heparin on Severe Sepsis With Suspected Disseminated Intravascular Coagulation
Official title: Phase 3 Study of the Efficacy and Safety of Unfractionated Heparin in Patients With Severe Sepsis/Septic Shock With Suspected DIC
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Sepsis
Disseminated Intravascular Coagulation
Keywords: Severe sepsis
Disseminated intravascular coagulation
Unfractionated heparin
Lead sponsor: China Medical University, China
Sponsor class: OTHER
Collaborators: name: West China Hospital
name: Zhongda Hospital
name: The First Affiliated Hospital of Dalian Medical University
name: Shengjing Hospital
name: The First Hospital of Jilin University
name: Qilu Hospital of Shandong University
name: The Second Affiliated Hospital of Kunming Medical University
name: The First Hospital of Qinhuangdao
name: The Second Affiliated Hospital of Dalian Medical University
name: First Affiliated Hospital of Harbin Medical University
name: Peking University People's Hospital
name: The People's Hospital of Liaoning Province
name: Fourth People's Hospital of Shenyang
name: Beijing Tsinghua Changgeng Hospital
name: First Affiliated Hospital of Kunming Medical University
name: The Affiliated Hospital of Qingdao University
name: Beijing Friendship Hospital
name: General Hospital of Ningxia Medical University
name: The First Affiliated Hospital of Nanchang University
First posted: 2016-01-13
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to estimate the efficacy of unfractionated heparin(UFH) on ICU mortality in severe sepsis with suspected DIC.The Second objective is to estimate the effect of UFH on 28-day mortality,and the change of the Japanese Association for Acute Medicine(JAAM) score and SOFA score. The third one is to evaluate the safety of UFH in severe sepsis patients with suspected DIC.

Detailed description: During the study, the whole process of data validation and registry procedures will be implemented by the Principal Investigator of the study, and monitored by the Ethics Committee of the First Affiliated Hospital of China Medical University.There are 2 research supervisors(2 ICU doctors) to assess the accuracy, completeness and representativeness of registry data, and to report the study process and research results to Principal Investigator.Investigators have also edited a data dictionary including each variable used by the registry and normal ranges of all detection indexes. The standard operating procedures have been formulated to address the registry and data analysis. The feasibility and significance have been assessed carefully and funded by the Health and Family Planning Commission of Liaoning Province(No.LNCC-B01-2014).The sample size is 600 participants through statistic calculation. The plan for missing data and statistical analysis will be implemented by specialized statisticians of China Medical University.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of severe sepsis or/and septic shock
* suspected DIC:the score of Platelets plus International Normalized Ratio in the JAAM criteria is equal or more than 3 scores

Exclusion Criteria:

* consent declined
* pregnant or breastfeeding
* the length during ICU is less than 24 hours
* with other types of shock
* have bleeding or high risk for bleeding
* have an indication for therapeutic anticoagulation
* have a known or suspected adverse reaction to UFH including HIT
* are currently enrolled in another trial
* known or suspected cirrhosis or other severe hepatic diseases
* terminal illness with a life expectancy of less than 28 days

Primary outcomes:
measure: ICU mortality
timeFrame: during ICU stay (up to day 28)
Secondary outcomes:
measure: 28-day all-cause mortality
timeFrame: after 28 days of enrollment of all the cases
measure: the incidence of major bleeding
timeFrame: during ICU stay (up to day 28)
Other outcomes:
measure: Change in SOFA scores
timeFrame: during the intervention period (up to day 7 after enrollment)
measure: Change in JAAM and ISTH scores
timeFrame: during the intervention period (up to day 7 upon enrollment)
Locations:
city: Haerbin
country: China
facility: The fist Affiliated Hospital Harbin Medical University
state: Heilongjiang
city: Changsha
country: China
facility: Xiangya Third Hospital of Central South University
state: Hunan
city: Nanjing
country: China
facility: Zhongda Hospital
state: Jiangsu
city: Dalian
country: China
facility: First Affiliated Hospital of Dalian Medical University
state: Liaoning
city: Dalian
country: China
facility: Second Affiliated Hospital of Dalian Medical University
state: Liaoning
city: Shenyang
country: China
facility: second Affiliated Hospital of china Medical University
state: Liaoning
city: Shenyang
country: China
facility: Shenyang Fourth People's Hospital
state: Liaoning
city: Qingdao
country: China
facility: Qilu Hospital of Shandong University（qingdao）
state: Shandong
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Kunming
country: China
facility: First Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Kunming
country: China
facility: the Second Affiliated Hospital of Kunming University
state: Yunnan
city: Beijing
country: China
facility: Beijing Friendship Hospital ， Capital Medical University
city: Beijing
country: China
facility: Changgeng Hospital of Tsinghua University
city: Beijing
country: China
facility: People's Hospital of Peking University
city: Jilin
country: China
facility: First Affiliated Hospital of Jilin Medical University
city: Qinhuangdao
country: China
facility: Qinhuangdao First Hospital
city: Shenyang
country: China
facility: Liaoning Provincial People's Hospital
Study officials:
References:
citation: Zhang XJ, Ma XC. [Therapeutic effects of early administration of low-dose heparin in patients with severe sepsis]. Zhonghua Wai Ke Za Zhi. 2006 Sep 1;44(17):1209-11. Chinese.
citation: Zhao C, Zhang ZD, Zhang XJ, Li X, Zhu R, Ma XC. [Evaluation of clinical effects on low-dose heparin therapy for sepsis]. Zhonghua Nei Ke Za Zhi. 2009 Jul;48(7):566-9. Chinese.
citation: Jaimes F, De La Rosa G, Morales C, Fortich F, Arango C, Aguirre D, Munoz A. Unfractioned heparin for treatment of sepsis: A randomized clinical trial (The HETRASE Study). Crit Care Med. 2009 Apr;37(4):1185-96. doi: 10.1097/CCM.0b013e31819c06bc.
citation: Liu XL, Wang XZ, Liu XX, Hao D, Jaladat Y, Lu F, Sun T, Lv CJ. Low-dose heparin as treatment for early disseminated intravascular coagulation during sepsis: A prospective clinical study. Exp Ther Med. 2014 Mar;7(3):604-608. doi: 10.3892/etm.2013.1466. Epub 2013 Dec 31.
citation: Barkun J, Christou NV; CAGS Evidence Based Reviews in Surgery Group. Canadian Association of General Surgeons Evidence Based Reviews in Surgery. 8. Efficacy and safety of recombinant human activated protein C for severe sepsis. Can J Surg. 2003 Dec;46(6):468-70. No abstract available.