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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
50
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 guideline-directed care for adult septic shock.
Lakeridge Health Ajax-Pickering
Ajax, Ontario, Canada
Lakeridge Health Oshawa
Oshawa, Ontario, Canada
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.
Time frame: 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.
Time frame: 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.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Enrolment