Efficacy and Safety of Unfractionated Heparin on Severe Sepsis With Suspected Disseminated Intravascular Coagulation

Sepsis Clinical Trial

Official title:

Phase 3 Study of the Efficacy and Safety of Unfractionated Heparin in Patients With Severe Sepsis/Septic Shock With Suspected DIC

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02654561
• Other study ID #: LNCCC-B01-2014
• Status: Recruiting
• Phase: Phase 3
• Start date: April 12, 2018
• Est. completion date: June 2025

Study information

• Verified date: November 2023
• Source: China Medical University, China
• Contact: Xiaochun Ma, M.D.
• Phone: 0086-13840192939
• Email: maxc_cmu[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: June 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Disseminated Intravascular Coagulation
• Sepsis
• Toxemia

Intervention

Drug:
• Heparin Sodium
A bottle solution of Heparin Sodium(2ml:12500IU) is added to 50ml saline and administered i.v. continuously for 24 hours, which last 7 days or until the death or discharge. The same amount of 0.9% saline as the heparin group will be administered in the placebo group.
• Saline
For all the severe sepsis or septic shock patients, normal saline will be administered for fluid resuscitation according to the Guideline of Survival Sepsis Campaign.

Locations

Country	Name	City	State
China	Beijing Friendship Hospital , Capital Medical University	Beijing
China	Changgeng Hospital of Tsinghua University	Beijing
China	People's Hospital of Peking University	Beijing
China	Xiangya Third Hospital of Central South University	Changsha	Hunan
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	First Affiliated Hospital of Dalian Medical University	Dalian	Liaoning
China	Second Affiliated Hospital of Dalian Medical University	Dalian	Liaoning
China	The fist Affiliated Hospital Harbin Medical University	Haerbin	Heilongjiang
China	First Affiliated Hospital of Jilin Medical University	Jilin
China	First Affiliated Hospital of Kunming Medical University	Kunming	Yunnan
China	the Second Affiliated Hospital of Kunming University	Kunming	Yunnan
China	Zhongda Hospital	Nanjing	Jiangsu
China	Qilu Hospital of Shandong University(qingdao)	Qingdao	Shandong
China	Qinhuangdao First Hospital	Qinhuangdao
China	Liaoning Provincial People's Hospital	Shenyang
China	second Affiliated Hospital of china Medical University	Shenyang	Liaoning
China	Shenyang Fourth People's Hospital	Shenyang	Liaoning

Sponsors (20)

Lead Sponsor

Collaborator

China Medical University, China

Beijing Friendship Hospital, Beijing Tsinghua Changgeng Hospital, First Affiliated Hospital of Harbin Medical University, First Affiliated Hospital of Kunming Medical University, Fourth People's Hospital of Shenyang, General Hospital of Ningxia Medical University, Peking University People's Hospital, Qilu Hospital of Shandong University, Shengjing Hospital, The Affiliated Hospital of Qingdao University, The First Affiliated Hospital of Dalian Medical University, The First Affiliated Hospital of Nanchang University, The First Hospital of Jilin University, The First Hospital of Qinhuangdao, The People's Hospital of Liaoning Province, The Second Affiliated Hospital of Dalian Medical University, The Second Affiliated Hospital of Kunming Medical University, West China Hospital, Zhongda Hospital

Country where clinical trial is conducted

China, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in SOFA scores	The difference of SOFA scores between day 7 and day 1 upon enrollment	during the intervention period (up to day 7 after enrollment)
Other	Change in JAAM and ISTH scores	The difference of JAAM and ISTH scores between day7 and day1 upon enrollment	during the intervention period (up to day 7 upon enrollment)
Primary	ICU mortality	The mortality during ICU stay	during ICU stay (up to day 28)
Secondary	28-day all-cause mortality	The all-cause mortality at day 28 after enrollment	after 28 days of enrollment of all the cases
Secondary	the incidence of major bleeding	"Major bleeding" is defined as intracranial bleeding, life-threatening bleeding, or need red blood cell suspension more than 3 units every 24 hours,and last for 2 days	during ICU stay (up to day 28)