Adjunctive Methylene Blue in Septic Shock

NCT ID: NCT06900140

Last Updated: 2025-06-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-02
• Study Completion Date: 2025-10-31

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.

Detailed Description

BACKGROUND: Septic shock remains an important cause of morbidity and mortality worldwide, and disproportionately affects low- and middle-income countries. The current standard of care in the treatment of septic shock is limited to antimicrobials and supportive care such as intravenous fluids, vasopressors, mechanical ventilation, and renal replacement therapy. Existing data from small randomized controlled trials suggests that methylene blue may be efficacious in reducing vasopressor exposure and mortality in patients with septic shock. Methylene blue is an inexpensive and readily available therapy which, if proven effective, could be used worldwide and drastically change outcomes in high- and low-income settings alike.

OBJECTIVES: Pilot trial to determine the feasibility of a large, open-label, multicentre randomized trial evaluating the efficacy and safety of intravenous methylene blue infusion, as compared to usual care, in adult patients with septic shock in the intensive care unit (ICU).

METHODS: Patients will be randomly assigned to methylene blue infusion (intravenous, dissolved in dextrose 5% in water, run at 0.5 mg/kg/hr over 6 hours daily) up to 3 days total, or usual care for septic shock. Study personnel at the clinical sites will document the composite of death or persistent organ dysfunction at day 28. Daily assessments will occur for organ function and vasopressor exposure. The trial will be conducted in two adult intensive care units at Lakeridge Health.

RELEVANCE: The BLUSH trial will test the feasibility of conducting a large randomized trial to evaluate the efficacy and safety of methylene blue in adult patients with septic shock.

Conditions

Septic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Methylene Blue

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

Group Type: EXPERIMENTAL

Methylene Blue

Intervention Type: 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.

Usual Care

Usual guideline-directed care for adult septic shock.

Group Type: ACTIVE_COMPARATOR

Usual Care

Intervention Type: OTHER

Usual guideline-directed care for adult septic shock.

Interventions

Methylene Blue

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.

Intervention Type: DRUG

Usual Care

Usual guideline-directed care for adult septic shock.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Adult patients (≥ 18 years of age) admitted to the ICU

2. 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).

3. 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).

Exclusion Criteria

1. > 48 hours since initiation of norepinephrine

2. > 48 hours since admission to ICU

3. Anticipation of discontinuation of vasopressors in < 24 hours

4. Pregnancy **Women of childbearing age (<50 years) should have a urine or beta hCG performed prior to enrolment

5. Plan for withdrawal of life support

6. Concurrent hemorrhagic, obstructive, or hypovolemic shock

7. Major burn injury (>10% total body surface area)

8. Known Personal or familial history of glucose-6-phophate dehydrogenase deficiency

9. Known Allergy to methylene blue, phenothiazines, or food dyes

10. Known recent intake of selective serotonin re-uptake inhibitors (21 days for norfluoxetine, and 14 days for any other SSRI).

11. Currently receiving linezolid

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dr. Shannon M. Fernando

OTHER

Sponsor Role: lead

Responsible Party

Dr. Shannon M. Fernando

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Shannon M Fernando, MD

Role: PRINCIPAL_INVESTIGATOR

Lakeridge Health

Locations

Lakeridge Health

Oshawa, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Shannon M Fernando, MD

Role: CONTACT

sfernando@lh.ca

905-576-8711

Facility Contacts

Kelly Fusco

Role: primary

kfusco@lh.ca

905-576-8711 ext. 32338

Other Identifiers

LHICU123

Identifier Type: -

Identifier Source: org_study_id