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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether methylene blue, a medication, can aid adults in the ICU with septic shock, a severe infection that causes dangerously low blood pressure. Participants will receive either methylene blue infusions or continue with standard care to determine which method improves patient outcomes. Those diagnosed with septic shock and receiving specific blood pressure support treatments might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that methylene blue is likely to be safe for humans?

Research has shown that methylene blue might be safe for people with septic shock. One study found it could reduce the time patients need medication to support blood pressure. Other studies suggest methylene blue might improve survival rates and shorten hospital stays for critically ill patients. However, some sources indicate that while the results are promising, more definitive evidence is needed to fully support its use. Overall, methylene blue appears well-tolerated, but it is important to consider all available information and consult a healthcare provider before deciding to join a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for septic shock?

Methylene Blue is unique because it offers a new approach to treating septic shock by targeting nitric oxide pathways, which are involved in the widening of blood vessels during septic shock. Unlike the standard treatments that primarily focus on stabilizing blood pressure with fluids and vasopressors, Methylene Blue acts as a vasoconstrictor, potentially offering faster stabilization of blood pressure. Researchers are excited about its potential to improve outcomes in septic shock patients by addressing the underlying cause of low blood pressure more directly.

What evidence suggests that methylene blue might be an effective treatment for septic shock?

Research suggests that methylene blue, which participants in this trial may receive, might help people with septic shock. It has raised blood pressure and reduced the need for other heart-supporting medications. Some studies found that it can also shorten the time patients spend in the intensive care unit (ICU) and on breathing machines. However, the evidence is not entirely consistent, and some experts believe more research is needed to confirm these benefits. Methylene blue improves blood flow and helps the body respond to severe infections. ^{4 6 7 8 9}

Who Is on the Research Team?

Shannon M Fernando, MD

Principal Investigator

Lakeridge Health

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11063345/

Methylene blue in sepsis and septic shock - PubMed Central

Summarizing these data, MB infusion improved hemodynamic status, decreased length of ICU stay, and days on mechanical ventilation. In addition, ...

2.

trialsjournal.biomedcentral.com

trialsjournal.biomedcentral.com/articles/10.1186/s13063-024-08439-5

Efficacy of methylene blue in refractory septic shock - Trials

Some previous studies have revealed that methylene blue could improve hypotension status and help reduce the dosage of catecholamines. This ...

3.

pulmonarychronicles.com

pulmonarychronicles.com/index.php/SWJM/article/view/1529/3145

Outcomes of methylene blue treatment in septic shock

Methylene blue consistently improved hemodynamic parameters, including mean arterial blood pressure and systemic vascular resistance. It did not ...

4.

cureus.com

cureus.com/articles/369370-methylene-blue-in-septic-shock-emerging-evidence-clinical-applications-and-future-directions

Methylene Blue in Septic Shock: Emerging Evidence, ...

While some promising results regarding reduced vasopressor requirements and length of stay are suggested, current evidence does not support ...

5.

journals.lww.com

journals.lww.com/ccejournal/fulltext/2024/07000/methylene_blue_in_septic_shock__a_systematic.2.aspx

Methylene Blue in Septic Shock: A Systematic Review and...

MB may decrease hospital length of stay (MD –2.1 d [95% CI, –1.4 to –2.8], low certainty), ICU length of stay (MD –1.05 d [95% CI, –2.6 to +0.5], low certainty) ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11196076/

Methylene Blue in Septic Shock: A Systematic Review and ...

MB may decrease hospital length of stay (MD –2.1 d [95% CI, –1.4 to –2.8], low certainty), ICU length of stay (MD –1.05 d [95% CI, –2.6 to +0.5] ...

7.

ccforum.biomedcentral.com

ccforum.biomedcentral.com/articles/10.1186/s13054-023-04397-7

Early adjunctive methylene blue in patients with septic shock

In patients with septic shock, MB initiated within 24 h reduced time to vasopressor discontinuation and increased vasopressor-free days at 28 days.

8.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1053077023008029

Methylene Blue Reduces Mortality in Critically Ill and ...

This meta-analysis showed that MB may improve survival in critically ill and perioperative patients, with reductions in ICU and hospital lengths of stay.

9.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06481410

Efficacy and Safety of Methylene Blue in the Treatment ...

The goal of this clinical trial is to investigate whether methylene blue injection can safely and effectively improve the survival rate of patients with severe ...