Methylene Blue for Septic Shock

(BLUSH Trial)

Overseen By Shannon M Fernando, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Dr. Shannon M. Fernando

Must not be taking: SSRIs, Linezolid

Disqualifiers: Pregnancy, G6PD deficiency, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 3 days

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking selective serotonin re-uptake inhibitors (SSRIs) at least 14 days before joining, and norfluoxetine 21 days before. You also cannot participate if you are currently taking linezolid.

What data supports the effectiveness of the drug methylene blue for treating septic shock?

Research shows that methylene blue can help increase blood pressure and reduce the need for other medications that raise blood pressure in patients with septic shock. However, its impact on survival rates is not well studied. ^{1 2 3 4 5}

Is methylene blue safe for use in humans?

Methylene blue has been used in humans with septic shock and generally increases blood pressure without major side effects, though it may cause some lung-related issues if not administered carefully. More research is needed to fully understand its safety profile. ^{1 6 7 8 9}

How does the drug methylene blue differ from other treatments for septic shock?

Methylene blue is unique because it works by inhibiting guanylate cyclase, which helps increase blood pressure in septic shock patients by counteracting nitric oxide's effects that cause blood vessels to widen. Unlike standard treatments, methylene blue is not widely used and is still being studied for its optimal timing, dosing, and safety in septic shock. ^{2 3 6 8 9}

What is the purpose of this 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.

Research Team

Shannon M Fernando, MD

Principal Investigator

Lakeridge Health

Eligibility Criteria

This trial is for adult patients in the intensive care unit diagnosed with septic shock. Specific eligibility criteria are not provided, but typically participants must meet certain health conditions and agree to follow study procedures.

Inclusion Criteria

Diagnosed with septic shock as per the Sepsis-3 Criteria

I am 18 or older and currently in the ICU.

I've been on a low dose of norepinephrine recently.

Exclusion Criteria

I have been in the ICU for more than 48 hours.

Pregnancy (Women of childbearing age should have a urine or beta hCG performed prior to enrollment)

Plan for withdrawal of life support

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive methylene blue infusion or usual care for septic shock

3 days

Daily assessments for 3 days

Follow-up

Participants are monitored for organ function and vasopressor exposure

28 days

Daily assessments

Treatment Details

Interventions

• Methylene Blue

Trial Overview The BLUSH trial is testing if methylene blue infusion as an additional treatment (adjunctive) can improve outcomes for patients with septic shock compared to usual care alone. It's a pilot study to see if a larger trial would be feasible.

Participant Groups

Group I: Methylene Blue Experimental Treatment 1 Intervention

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

Group II: Usual Care Active Control 1 Intervention

Usual guideline-directed care for adult septic shock.

Who Is Running the Clinical Trial?

Dr. Shannon M. Fernando

Lead Sponsor

Trials

1

Recruited

30+

References

1. United States pubmed.ncbi.nlm.nih.gov

Use of methylene blue in sepsis: a systematic review. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Prolonged methylene blue infusion in refractory septic shock: a case report. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Effect of methylene blue on hemodynamic and metabolic response in septic shock patients. [2023]

5. Israel pubmed.ncbi.nlm.nih.gov

Methylene Blue Administration for Distributive Shock States in Critically Ill Children. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Effect of methylene blue on hemodynamic response in the early phase of septic shock: A case series. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Use of methylene blue in patients with refractory septic shock: impact on hemodynamics and gas exchange. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Methylene blue--a promising treatment modality in sepsis induced by bowel perforation. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Methylene blue for the treatment of septic shock. [2022]