Early Methylene Blue in the Microhemodynamics of Septic Patients

NCT07264543 | Recruiting Phase 2

• 3 other identifiers: U1111-1331-7627Approval number 7.955.174CAAE 93099325.5.0000.0020
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study is to evaluate the viability and feasibility of its protocol in order to conduct a larger clinical trial to assess whether methylene blue can improve patient-centered clinical outcomes such as mortality or length of hospital stay in septic shock patients.

Conditions

Septic Shock; Hypoperfusion

Keywords

Septic Shock; Methylene Blue; Microcirculation; Capillary Refill Time

Outcome Measures

Primary Outcomes (1)

• To evaluate the feasibility of the study protocol.

  The primary outcome of the study is to evaluate feasibility, defined as completing the study protocol according to the planned timeline and with 90% or more protocol adherence. Protocol adherence will be defined as the use of the allocated therapy in the intervention group for 6 hours for 3 days (or interruption of methylene blue if the patient does not require a vasoactive drug anymore). Justified interruptions will not be considered violations.

  28 days after randomization.

Secondary Outcomes (10)

• Capillary refill time

  72 hours after randomization.

• Serum lactate level

  72 hours after randomization.

• Arteriovenous carbon dioxide difference (gapCO2)

  72h after randomization.

• Central venous oxygen saturation (SvO2)

  72h after randomization.

• Serial measurements of heart rate

  72 hours after randomization.

Other Outcomes (7)

• Variations in the Sequential Organ Failure Assessment-2 Score (SOFA-2)

  From enrollment to 72 hours later.

• Time to vasopressor discontinuation

  28 days after randomization.

• Vasopressor dose (norepinephrine and vasopressin)

  72 hours after randomization.

Study Arms (2)

Methylene blue group

EXPERIMENTAL

The intervention group will receive methylene blue plus standard treatment for septic shock, according to the international guidelines.

Drug: Methylene blue infusion

Control group

NO INTERVENTION

The control group will receive the standard treatment according to international guidelines for the management of sepsis and septic shock.

Interventions

Methylene blue infusion DRUG

Methylene blue at a dose of 100mg (diluted in 100ml of 5% dextrose solution) in continuous infusion for 06 hours per day, for 03 days, plus standard treatment according to international guidelines for the management of sepsis and septic shock. The 03 consecutive MB infusions, each lasting 06 hours, will be performed every 24 hours, starting from randomization: the first infusion at T0, the second at T24, and the third at T48, considering T0 the moment after the patient randomization into the study. The interruption of the protocol will be recommended if vasopressors are completely discontinued during the three days of methylene blue infusion. The attending physician may discontinue methylene blue treatment if judges necessary. Similarly, interruption may occur if the family or patient request.

Also known as: Methylene blue, Phenothiazines

Methylene blue group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva: lead
• Irmandade da Santa Casa de Misericordia de Curitiba: collaborator

Study Sites (1)

Irmandade da Santa Casa de Misericórdia de Curitiba

Curitiba, Paraná, 80010-030, Brazil

RECRUITING

MeSH Terms

Conditions

Shock, Septic

Interventions

Methylene Blue; Phenothiazines

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Álvaro Réa-Neto

  CEPETI - Centro de Estudos e Pesquisa em Emergências Médicas e Terapia Intensiva

  STUDY CHAIR

Central Study Contacts

Bruna Dal Vesco

CONTACT

+55 (41) 3362-6633; brunadalvesco@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Due to the high probability of the intervention group present blue coloured skin and secretions caused by MB infusion, the study is classified as open-label for patients, assisting staff and investigators. Blinding remains for the team that will perform the statistical analysis.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Research Fellow

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: December 4, 2025
• Study Start: January 9, 2026
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)