Methylene Blue in Severe Sepsis and Septic Shock

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

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

Study Overview

• Status: Unknown
• Conditions: Septic Shock; Severe Sepsis
• Intervention / Treatment: Drug: Placebo; Drug: Intravenous methylene blue administration

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 354
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul National University Hospital
    • Contact: Kyuseok Kim; Phone Number: +82-31-787-7572; Email: dremkks@snubh.org
  • Seoul, Korea, Republic of
    • Recruiting
    • SMG - SNU Boramae Medical Center
    • Contact: Kyuseok Kim; Phone Number: +82-31-787-7572; Email: dremkks@snubh.org
  • Kyeongi-do
    • Seongnam-si, Kyeongi-do, Korea, Republic of
      • Recruiting
      • Seoul National University Bundang Hospital
      • Contact: Kyuseok Kim, MD; Phone Number: +82-31-787-7572; Email: dremkks@snubh.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Study Director: Kyuseok Kim, MD, Professor, department of emergency medicine

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Anticipated): January 1, 2016
• Study Completion (Anticipated): March 1, 2017

Study Registration Dates

• First Submitted: February 21, 2013
• First Submitted That Met QC Criteria: February 22, 2013
• First Posted (Estimate): February 25, 2013

Study Record Updates

• Last Update Posted (Estimate): November 18, 2015
• Last Update Submitted That Met QC Criteria: November 16, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Septic shock; Sepsis; Methylene blue
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia; Shock, Septic; Shock; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Methylene Blue
• Other Study ID Numbers: B-1210/173-002