Early Methylene Blue in the Microhemodynamics of Septic Shock Patients

Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva

Status and phase

Enrolling

Phase 3

Phase 2

Conditions

Hypoperfusion

Septic Shock

Treatments

Drug: Methylene blue infusion

Study type

Interventional

Funder types

Other

Identifiers

NCT07264543

Approval number 7.955.174 (Other Identifier)

CAAE 93099325.5.0000.0020 (Other Identifier)

U1111-1331-7627

Details and patient eligibility

About

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.

Full description

One of the primary causes of high mortality in patients with septic shock is microcirculatory dysfunction related to vasodilation caused by excessive oxide nitric production. It has been shown that methylene blue, an old and safe drug that can reduce vasodilation by blocking nitric oxide pathways, is a vasopressor-sparing treatment in sepsis. Nevertheless, there is no evidence that methylene blue improves patient-centered clinical outcomes such as mortality. Understanding how early methylene blue affects the microhemodynamics of septic shock patients may lead to relevant clinical results that can improve their prognosis. So, the objective of the study is to evaluate the viability and feasibility of the study protocol for a larger clinical trial, assessing the effectiveness of early methylene blue in the microhemodynamics of septic shock patients, mainly through the capillary refill time measurement. For this purpose, a pilot study of an open-label, randomized, controlled and single-center clinical trial will be conducted, with two treatment arms: the intervention group (methylene blue plus standard treatment) and the control group (standard treatment). Fifty adult patients with septic shock within the first six hours of diagnosis will be included in this study. They will be randomized to either receive a methylene blue infusion or not. The randomization will be conducted using RedCap with a 1:1 ratio and variable block sizes. The primary outcome will be to assess the feasibility, which is defined as completing the study recruitment within the 12-month timeline and achieving protocol adherence of 90% or higher. Comparisons between groups for serially measured micro and macrohemodynamics parameters will be the secondary outcomes. Additionally, the incidence of adverse events related to methylene blue will be monitored.

Enrollment

50 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Adult patients diagnosed with septic shock according to SEPSIS-3 definition, within less than 6 hours of the diagnosis.

Exclusion criteria

Pregnant or breastfeeding patients;
Patients with any withdrawal or withholding life-sustaining intervention;
Cardiac surgery patients in the immediate postoperative period;
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.