Methylene Blue for the Treatment of Septic Shock

Initiation of Methylene Blue for Septic Shock in Adults: A Randomized Clinical Trial

The purpose of this study is to evaluate the efficacy and safety of methylene blue among adult patients with septic shock.

Study Overview

• Status: Completed
• Conditions: Septic Shock
• Intervention / Treatment: Drug: Methylene Blue; Drug: Placebo

Detailed Description

Septic Shock is a leading cause of morbidity and mortality in critically ill patients worldwide.

A potential benefit of methylene blue in the treatment of septic shock has recently been described by Estrada. In patients with septic shock, methylene blue initiated within 24 h reduced time to vasopressor discontinuation and increased vasopressor-free days at 28 days. It also reduced length of stay in ICU and hospital without adverse effects.

In this randomized controlled trial, we aim to evaluate the efficacy and safety of methylene blue on septic shock.

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Yangzhou, Jiangsu, China, 225000
      • Northern Jiangsu People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. age 18 years old or older;
2. diagnosis of septic shock within 12 h.

Exclusion Criteria:

1. recent intake (4-weeks) of selective serotonin re-uptake inhibitors;
2. pregnant;
3. definitive pulmonary hypertension or chronic pulmonary heart disease;
4. known glucose-6 phosphate dehydrogenase (G-6PD) deficiency;
5. known allergy to methylene blue, phenothiazines, or food dyes;
6. anticipated death from a preexisting disease within 90 days after randomization (as determined by the enrolling physician);
7. refusal of the attending staff or patient family;
8. participated in other study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methylene Blue; Methylene Blue 100mg will be diluted in 40ml 5% dextrose solution. Methylene Blue(1 mg/kg/IBW iv over 30min+0.25mg/kg/h x 6h) x 5-days/ discontinution of norepinephrine /ICU discharge (whichever occurred first).	Drug: Methylene Blue; Methylene Blue 100mg will be diluted in 40ml 5% dextrose solution.The patient will receive Methylene Blue bolus with a dose of 1 mg/kg (Ideal Body Weight) over 30 minutes,followed by 0.25mg/kg/h as a continuous infusion for 6 hours for 5 days or discontinution of norepinephrine or until ICU discharge, whichever occurred first.; Other Names: MB
Placebo Comparator: Placebo; 5% dextrose solution in a volume to match experimental arm component.	Drug: Placebo; An identical volume of 5% dextrose solution from the placebo drug bag will be administered to patients using the same protocol as intervention arm.; Other Names: 5%GS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to shock reversal	Time to shock reversal was defined as the time from randomization to shock reversal.Reversal of shock was defined as the maintenance of a systolic blood pressure of at least 90 mmHg without vasopressor support for at least 24 h.	90 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU mortality	All-cause mortality at ICU discharge	90 days after randomization
Hospital mortality	All-cause mortality at hospital discharge	90 days after randomization
28-day mortality	All-cause mortality at day 28 after randomization	28 days after randomization
90-day mortality	All-cause mortality at day 90 after randomization	90 days after randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU length of stay	Time in days until ICU discharge	90 days after randomization
hospital length of stay	Time in days until hospital discharge	90 days after randomization
ICU-free days up to day 28	Total number of days alive and free of ICU stay during the 28 days after randomization.	28 days after randomization
vasopressor-free days up to day 28	Total number of days alive and free of vasopressor during the 28 days after randomization.	28 days after randomization
ventilator support-free days up to day 28	Total number of days alive and free of ventilator support during the 28 days after randomization.	28 days after randomization
CRRT-free days up to day 28	Total number of days alive and free of CRRT during the 28 days after randomization.	28 days after randomization
72h lactate	lactate level at 72h after randomization	72 hours after randomization
72h Delta SOFA	Initial SOFA score at enrollment-SOFA score after 72 h;If the patient discharged within 72 h after being enrolled in the study, the SOFA score at discharge was used for the analysis.	72 hours after randomization
72h P/F	P/F at 72h after randomization	72 hours after randomization

Collaborators and Investigators

• Sponsor: Northern Jiangsu People's Hospital
• Investigators: Principal Investigator: Qingquan Lyu, Master, Northern Jiangsu People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2024
• Primary Completion (Actual): October 24, 2025
• Study Completion (Actual): October 24, 2025

Study Registration Dates

• First Submitted: July 29, 2024
• First Submitted That Met QC Criteria: July 29, 2024
• First Posted (Actual): August 1, 2024

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: septic shock; mortality; methylene blue
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Pathological Conditions, Signs and Symptoms; Shock, Septic; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Phenothiazines; Methylene Blue
• Other Study ID Numbers: 2024ky202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No