Adjunctive Methylene Blue in Septic Shock

NCT06900140 | Completed Phase 3 DMC

• 1 other identifier: LHICU123
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

Adjunctive Methylene BLUe in Septic SHock (BLUSH) is a single centre concealed-allocation parallel-group open-label randomized controlled pilot trial to ascertain the feasibility of a trial evaluating the efficacy and safety of adjunctive methylene blue infusion compared to usual care on outcomes of adult patients admitted to the intensive care unit with septic shock.

Conditions

Septic Shock

Keywords

Septic shock; Methylene blue

Outcome Measures

Primary Outcomes (3)

• Enrolment/Recruitment Rate

  The investigators define a successful recruitment rate of 1 patient per centre per month over the duration of the trial. The recruitment will be reviewed weekly and the screening logs will be reviewed monthly. This will be done to ensure that enrolment is being maximized and that any barriers are being addressed. A recruitment metric will be measured and interpreted at the end of the trial. Excluded patients and eligible non-randomized patients will be reviewed to determine whether any modifications to the protocol may be warranted, or to address implementation challenges. Barriers to enrolment will be discussed and strategies to improve enrolment will be operationalized, if needed.

  Enrolment

• Consent Rate

  The investigators will define \>50% consent rate as successful. This will be calculated as the overall proportion of patients/substitute decisions makers (SDMs) who consented to the trial out of everyone who was approached. If a patient or SDM chooses to withdraw from the study but allows for the data that had been collected up until that point to be used for analysis, they will still be counted as providing consent. Reasons for withdrawal will be recorded. The consent rate will be reviewed weekly and any barriers to consent that are identified will be addressed to improve the consent process.

  Enrolment

• Protocol Adherence

  The investigators will define ≥80% protocol adherence as successful. The adherence will be calculated as the number of patients who received allocated therapy per eligible study day over all the eligible study intervention days across enrolled patients. Each enrolled patient will contribute 3 eligible study intervention days unless they meet discontinuation criteria (e.g., stopped vasopressors). The research coordinator will review the chart to determine the actual compliance, and document all the reasons for non-compliance of both the control and experimental arms of the study. Furthermore, the study drug being discontinued and then re-started in a study patient would also not be deemed a protocol violation. Adherence will also be reviewed monthly and the reasons for compliance failure will be investigated and recorded as a protocol violation. Further behavioural strategies will be employed to improve adherence, if needed.

  Enrolment

Study Arms (2)

Methylene Blue

EXPERIMENTAL

Methylene Blue infusion: 0.5 mg/kg/hr for 6 hours daily (up to 3 days total).

Drug: Methylene Blue

Usual Care

ACTIVE COMPARATOR

Usual guideline-directed care for adult septic shock.

Other: Usual Care

Interventions

Usual Care OTHER

Usual guideline-directed care for adult septic shock.

Usual Care

Methylene Blue DRUG

Continuous methylene blue infusion at a fixed dose of 0.50 mg/kg/hour (diluted in 500 mL of dextrose 5% in water) over 6 hours once daily, for a total of up to 3 doses.

Methylene Blue

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (≥ 18 years of age) admitted to the ICU
• Diagnosed with septic shock (as per the Sepsis-3 Criteria): Suspected infection (i.e. initiation of antimicrobial therapy), coupled with initiation of vasopressor therapy to target a mean arterial pressure (MAP) \> 65 mmHg (or as prescribed by the treating clinician), after adequate fluid resuscitation (as per treating clinician).
• Minimal norepinephrine dose of 0.1 mcg/kg/min for a minimum of 2 hours at the time of enrollment (i.e., the time of randomization).

You may not qualify if:

• \> 48 hours since initiation of norepinephrine
• \> 48 hours since admission to ICU
• Anticipation of discontinuation of vasopressors in \< 24 hours
• Pregnancy \*\*Women of childbearing age (\<50 years) should have a urine or beta hCG performed prior to enrolment
• Plan for withdrawal of life support
• Concurrent hemorrhagic, obstructive, or hypovolemic shock
• Major burn injury (\>10% total body surface area)
• Known Personal or familial history of glucose-6-phophate dehydrogenase deficiency
• Known Allergy to methylene blue, phenothiazines, or food dyes
• Known recent intake of selective serotonin re-uptake inhibitors (21 days for norfluoxetine, and 14 days for any other SSRI).
• Currently receiving linezolid

Sponsors & Collaborators

• Dr. Shannon M. Fernando: lead

Study Sites (2)

Lakeridge Health Ajax-Pickering

Ajax, Ontario, Canada

Location

Lakeridge Health Oshawa

Oshawa, Ontario, Canada

Location

MeSH Terms

Conditions

Shock, Septic

Interventions

Methylene Blue

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Phenothiazines; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Shannon M Fernando, MD

  Lakeridge Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 20, 2025
• First Posted: March 28, 2025
• Study Start: June 2, 2025
• Primary Completion: March 6, 2026
• Study Completion: March 6, 2026
• Last Updated: March 19, 2026

Record last verified: 2026-03

Locations

CA (2)