Safety and Efficacy of Early Administration of Dexamethasone in High-risk Sepsis

Study Overview
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Brief Summary
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The purpose of this study is to investigate the safety and efficacy of early administration of two different doses of dexamethasone in high risk septic patients.

Detailed Description
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The septic adult patients of high risk would be enrolled in 2 emergency departments. Sepsis would be defined by Sepsis-3 definition. High risk is defined as initial systolic blood pressure less than 90 mmHg or blood lactate level over 2 mmol/L. The enrolled patients would be randomized to 3 groups: control, low dose dexamethasone (0.1 mg/kg iv), and high dose dexamethasone (0.2mg/kg iv). The study drug is blinded and administered after enrollment for 2 days. Sample size would be 102, considering 10% of drop-out rate, allocating 30 patients to each groups. Efficacy would be evaluated as follows; 28 day and 90 day mortality, time to septic shock, time to shock reversal, administration of steroid according to guideline, ventilator free days, Continuous renal replacement, Length of stay in ICU or hospital, delta SOFA score on day 3 and day 7, Safety would be evaluated as follows; Superinfection Gastrointestinal bleeding, Hyperglycemia, Hypernatremia

Official Title
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A Randomized, Double-blind, Multi-center Clinical Trial to Evaluate the Safety and Efficacy of Early Administration of Dexamethasone in High-risk Sepsis

Conditions
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Sepsis

Intervention / Treatment
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* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sepsis defined by Sepsis-3 definition Initial systolic blood pressure < 90mmHg or blood lactate level >2mmol/L Exclusion Criteria: advanced directive for Do not resuscitation recent systemic administration of glucocorticoid (4 weeks) recent systemic administration of chemotherapy (4 weeks) recent systemic administration of immunosuppressant (4 weeks) expected life less than 90 days Transferred from other hospital Sepsis diagnosed 24 hours after ED admission Use of etomidate in ED pregnant or on lactation no informed consent

Ages Eligible for Study
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Minimum Age: 19 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 |
| --- | --- |
| No Intervention: Placebo<br>normal saline | |
| Experimental: low dose dexamethasone<br>0.1 mg/kg dexamethasone iv once per day, for 1 or 2 days | Drug: Dexamethasone<br>* Intervention drugs would be administered for 1 or 2 days.<br>* Other names: JEIL Dexamethasone Injection;|
| Experimental: high dose dexamethasone<br>0.2 mg/kg dexamethasone iv once per day, for 1 or 2 days | Drug: Dexamethasone<br>* Intervention drugs would be administered for 1 or 2 days.<br>* Other names: JEIL Dexamethasone Injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28 day mortality | death at 28 day | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 90 day mortality | death at 90 day | 90 days | 
| Time to septic shock | Time to septic shock after enrollment | up to 1 month, During hospital stay | 
| Time to shock reversal | time required for shock reversal | up to 1 month, During hospital stay | 
| Administration of steroid according to guideline, yes or no | Need for additional steroid requirement according to the sepsis guideline | up to 1 month, During hospital stay | 
| ventilator free days | days independent from ventilator care | up to 3 month, During hospital stay | 
| continuous renal replacement therapy (CRRT) | requirement of CRRT | up to 3 month, During hospital stay | 
| Length of stay in intensive care unit (ICU) | Days spent in intensive care unit (ICU) | up to 6 month, During hospital stay | 
| Length of stay in hospital | Days spent in hospital | up to 6 month, During hospital stay | 
| Delta SOFA sore on day 3 and 7 | Change of SOFA score on day 3 and day 7 | 7 days | 
| Superinfection | secondary infection | 28 days | 
| Gastrointestinal bleeding | Gastrointestinal bleeding at any amount | 14 days | 
| Hyperglycemia | serum glucose >150 mg/dL | 7 days | 
| Hypernatremia | serum sodium >150mmol/L | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sepsis, glucocorticoid