Early methylene blue to improve microcirculation in septic shock

Evaluation of Early Methylene Blue in the Microhemodynamics of Septic Patients: a Feasibility Randomized Controlled Trial

This test will try giving methylene blue early to adults with septic shock to see if it improves blood flow in tissues and outcomes like survival or hospital stay.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva (Academic / other)
• Locations: 1 site (Curitiba, Paraná)
• Trial ID: NCT07264543 on ClinicalTrials.gov

What this trial studies

This is an open-label, randomized, controlled, single-center pilot of 50 adult patients with septic shock enrolled within six hours of diagnosis. Participants are randomized 1:1 to receive an infusion of methylene blue plus standard care or standard care alone. The study focuses on early effects of methylene blue on microhemodynamics, using capillary refill time and related measures, and is designed to evaluate feasibility of the protocol for a larger trial. The trial will also record clinical outcomes such as vasopressor requirements, length of stay, and mortality to inform a subsequent definitive study.

Who should consider this trial

Good fit: Adults diagnosed with septic shock or persistent hemodynamic dysfunction despite fluids who require escalation of norepinephrine and who can be enrolled within six hours of diagnosis are ideal candidates.

Not a fit: Patients with G6PD deficiency, pregnancy or breastfeeding, allergy to methylene blue or related agents, recent linezolid or certain serotonergic drugs, immediate postoperative cardiac surgery patients, or those with refractory shock expected to die within 24 hours are unlikely to be eligible or to benefit.

Why it matters

Potential benefit: If successful, early methylene blue could improve tissue perfusion, reduce vasopressor needs, shorten ICU or hospital stay, and possibly lower mortality in septic shock.

How similar studies have performed: Previous studies and case series have shown methylene blue can reduce vasodilation and lower vasopressor requirements, but there is no clear evidence yet that it improves survival or other patient-centered outcomes.

Eligibility criteria

Inclusion Criteria:

* Adult patients with a diagnosis of sepsis and persistent hemodynamic dysfunction despite adequate fluid resuscitation, requiring escalation of noradrenaline dose to maintain mean arterial pressure ≥65 mmHg, with prolonged capillary refill time or septic shock according to Sepsis-3 definition, within less than 6 hours of the diagnosis, will be eligible for the study.

Exclusion Criteria:

* Pregnant or breastfeeding patients;
* Patients with any withdrawal or withholding life-sustaining intervention;
* Cardiac surgery patients in the immediate postoperative period;
* Refractory septic shock, with a high propability of death within 24 hours;
* Personal or familiar history of glucose-6-phosphate dehydrogenase (G6PD) deficiency;
* Allergy to methylene blue, phenothiazines, or food dyes;
* Recent administration of linezolid (less than 14 days ago);
* Recent intake of serotonergic psychiatric medications (less than 2 weeks ago - with the exception of fluoxetine, which must be less than 5 weeks ago),
* Recent intake (less than 2 weeks ago) of monoamine oxidase inhibitors (MAOIs), such as rasagiline and selegiline.

Where this trial is running

Curitiba, Paraná

• Irmandade da Santa Casa de Misericórdia de Curitiba — Curitiba, Paraná, Brazil (Recruiting)

Study contacts

• Study coordinator: Bruna Dal Vesco

Conditions Septic Shock; Hypoperfusion; Methylene Blue; Microcirculation; Capillary Refill Time