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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Sepsis, Disseminated Intravascular Coagulation

Intervention / Treatment
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* Drug: Heparin Sodium
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Saline<br> | Drug: Saline<br>* 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.<br>* Other names: Normal saline;|
| Experimental: Heparin<br>If severe sepsis with suspected DIC is diagnosed, the Heparin sodium(2ml:12500 units) will be administered intravenously continuously for 24 hours. The course of treatment will last 7 days or until the death or discharge. | Drug: Heparin Sodium<br>* 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.<br>* Other names: Unfractionated heparin;Drug: Saline<br>* 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.<br>* Other names: Normal saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU mortality | The mortality during ICU stay | during ICU stay (up to day 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-day all-cause mortality | The all-cause mortality at day 28 after enrollment | after 28 days of enrollment of all the cases | 
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe sepsis, Disseminated intravascular coagulation, Unfractionated heparin