Methylene Blue in Severe Sepsis and Septic Shock

Study Overview
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Brief Summary
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This study is to see whether the intravenous administration of methylene blue improves the outcome in severe sepsis and septic shock.

Detailed Description
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The mortality of septic shock is still high ranging from 30 to 50%. Vasopressor is the main part in managing septic shock, but the choice of vasopressor is still under-investigated, and area of uncertainty. The response to vasopressor is sometimes unsatisfactory, and in that case, the outcome of the patients is poor. Recently, small size clinical trial has investigated the effect of methylene blue (MB), and showed promising results. However, large sized phase III trial has not been performed yet. Large sized phase III clinical trial is needed to establish the effect of MB in septic shock.

Official Title
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Infusion of Methylene Blue in Severe Sepsis and Septic Shock: Randomized, Single Blinded

Conditions
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Severe Sepsis, Septic Shock

Intervention / Treatment
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* Drug: Intravenous methylene blue administration
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Septic shock meeting the criteria of 2012 surviving sepsis campaign Need the norepinephrine of over 0.2microgram/kg/min Exclusion Criteria: Pregnancy Less than 18 years old Terminal cancer patients Declined consents glucose-6-phosphate dehydrogenase deficiency Medication of Serotonin modulator

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous methylene blue administration<br>2mg/kg IV bolus followed by 0.5mg/kg/hr slow infusion for 6hrs | Drug: Intravenous methylene blue administration<br>* Initial history taking and physical examination --> enrollment --> 2mg/kg IV bolus followed by 0.5mg/kg/hr slow infusion of methylene blue for 6hrs<br>* Other names: MB administration;|
| Placebo Comparator: Placebo<br>Normal saline administration instead of methylene blue | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28 day mortality |  | within 28 days of diagnosis | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vasopressor dependent period |  | within 28 days of diagnosis | 
| Vasopressor index |  | with in 28 days of diagnosis | 
| Change of cardiac output (CO) and systemic vascular resistance (SVR) | EV1000 (Edwards inc.) will be used to see the cardiac output and systemic vascular resistance. | with in 28 days of diagnosis | 
| Length of stay in ICU (LOSICU) |  | with in 28 days of diagnosis | 
| LOS in hospital |  | with in 28 days of diagnosis | 
| In hospital mortality |  | with in 28 days of diagnosis | 
| Multiple organ failure (SOFA) |  | with in 28 days of diagnosis | 
| NO level |  | before and after infusion of MB, 24hrs, 48hrs later | 
| Cytokine level (IL-6, 10, tumor necrosis factor -alpha) |  | before and after infusion of MB, 24hrs, 48hrs later | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sepsis, Septic shock, Methylene blue