Clinical trial NCT06900140: Adjunctive Methylene Blue in Septic Shock
Official title: Adjunctive Methylene BLUe in Septic SHock: a Pilot Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Septic Shock
Keywords: Septic shock
Methylene blue
Lead sponsor: Lakeridge Health
Sponsor class: OTHER
First posted: 2025-03-28
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Enrolment/Recruitment Rate
timeFrame: Enrolment
measure: Consent Rate
timeFrame: Enrolment
measure: Protocol Adherence
timeFrame: Enrolment
Secondary outcomes:
Other outcomes:
Locations:
city: Oshawa
country: Canada
facility: Lakeridge Health
state: Ontario
Study officials:
affiliation: Lakeridge Health
name: Shannon M Fernando, MD
role: PRINCIPAL_INVESTIGATOR
References: