Septic ShockPhase 3BLUSHNCT06900140
Adjunctive Methylene Blue in Septic Shock
A Phase 3 study testing Methylene Blue in people with Septic Shock, run by Dr. Shannon M. Fernando at 2 sites in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock
- What is being tested?
- Methylene Blue
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesCanada
- Study dates
- 2 Jun 2025to 6 Mar 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- > 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
Show all 11Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Lakeridge Health Ajax-Pickering
Ajax, Ontario
Lakeridge Health Oshawa
Oshawa, Ontario
About this study
Official title: Adjunctive Methylene BLUe in Septic SHock: a Pilot Randomized Controlled Trial
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.
Read the 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
- Being tested
- Methylene Blue, Usual Care
- Keywords
- Septic shock, Methylene blue
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylene BlueDrug
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 CareOther
Usual guideline-directed care for adult septic shock.
| Study group | Role | What they receive |
|---|---|---|
| Methylene Blue | Experimental | Methylene Blue infusion: 0.5 mg/kg/hr for 6 hours daily (up to 3 days total). Receives: Drug: Methylene Blue |
| Usual Care | Active comparator | Usual guideline-directed care for adult septic shock. Receives: Other: Usual Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Enrolment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2025
- Study start2 Jun 2025
- Primary completion6 Mar 2026
- Study completion6 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Shannon M. Fernando
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dr. Shannon M. Fernando, Lakeridge Health
- Investigators
- Shannon M Fernando, MD, Principal investigator, Lakeridge Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06900140
- Sponsor's protocol ID
- LHICU123
- Acronym
- BLUSH
- Status last verified
- Mar 2026
- First submitted
- 20 Mar 2025
- Last updated
- 19 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjunctive Methylene BLUe in Septic SHock: a Pilot Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT06900140
- Acronym / sponsor ID
- BLUSH / LHICU123
- Conditions
- Septic Shock
- Keywords
- Septic shock, Methylene blue
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Dr. Shannon M. FernandoUniversity, hospital or other
- Study start
- 2 Jun 2025 (actual)
- Primary completion
- 6 Mar 2026 (actual)
- Study completion
- 6 Mar 2026 (actual)
- First posted
- 28 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methylene Blue | Experimental | Drug: Methylene BlueMethylene Blue infusion: 0.5 mg/kg/hr for 6 hours daily (up to 3 days total). |
| Usual Care | Active comparator | Other: Usual CareUsual guideline-directed care for adult septic shock. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (11 listed)
- > 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methylene BlueContinuous 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. | Drug | Methylene Blue |
| Usual CareUsual guideline-directed care for adult septic shock. | Other | Usual Care |
Primary outcome
Enrolment/Recruitment Rate
Time frame: Enrolment
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.
Consent Rate
Time frame: Enrolment
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.
Protocol Adherence
Time frame: Enrolment
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shannon M Fernando, MD principal investigator
Lakeridge Health
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Methylene Blue in people with Septic Shock, run by Dr. Shannon M. Fernando at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Enrolment/Recruitment Rate (time frame: Enrolment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2026.