Septic shock Sepsis
Conditions
Interventions
Pilot study of an open-label, randomized, controlled, single-center clinical trial with two treatment arms: intervention group (methylene blue plus standard treatment) and control group (standard trea
Sponsors
Hospital Santa Casa de Curitiba
Centro de Estudos e Pesquisa em Emergências Médicas e Terapia Intensiva
Eligibility
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Patients aged 18 years or older; diagnosis of septic shock (defined as organ dysfunction with a Sequential Organ Failure Assessment (SOFA) score of 2 points or greater, caused by a dysregulated host response to infection and with persistent hypotension requiring vasopressor therapy to maintain mean arterial pressure at 65 mmHg or higher, and serum lactate level exceeding 2 mmol/L despite adequate fluid resuscitation); or 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; and less than 6 hours from the diagnosis.
Exclusion criteria
Exclusion criteria: Pregnant or breastfeeding patients; patients with any withdrawal or withholding life sustaining treatment status; patients in the immediate postoperative period following cardiac surgery; refractory septic shock, with a high propability of death within 24h; personal or familiar history of glucose-6-phosphate dehydrogenase deficiency; allergy to methylene blue, phenothiazines or food dyes; recent linezolid administration (within 14 days); recent intake of psychiatric medications with serotonergic activity (within 2 weeks, with the exception of fluoxetine requiring a 5-week washout period), including but not limited to paroxetine, fluoxetine, sertraline, citalopram, escitalopram, venlafaxine, desvenlafaxine, duloxetine, amitriptyline, imipramine, nortriptyline, trazodone, bupropion, buspirone, and mirtazapine; and recent use of monoamine oxidase inhibitors (MAOIs) such as rasagiline and selegiline within 2 weeks of enrollment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the feasibility, which is defined as completing study recruitment according to the planned timeline (12 months) and achieving protocol adherence of 90% or greater. Protocol adherence will be defined as the utilization of study-allocated therapy in the intervention group for 6 hours over 3 days (or discontinuation of methylene blue if the patient no longer requires vasoactive drugs). Justified interruptions will not be considered protocol violations. | — |
Secondary
| Measure | Time frame |
|---|---|
| A statistically significant difference in capillary refill time is expected to be found, measured serially from randomization up to 72 hours after, between control and intervention groups, with a statistical significance level of 5% and a 95% confidence interval, assessed through linear mixed-effects model, with random intercept by patient and group-by-time interaction terms, to account for the repeated measures structure. Considering the pilot design and the anticipated sample of 50 patients, the analyses will be essentially exploratory and descriptive in nature, with emphasis on estimating effect magnitude and measurement variability, providing parameters for sample size calculation of a future larger-scale clinical trial.;To verify whether there is a statistically significant difference in the comparison between intervention and control groups regarding other indicators of microhemodynamic status: daily serum lactate levels, arteriovenous carbon dioxide difference, and central venous oxygen saturation, for 3 days since the randomization. Statistical analyses will follow the same model proposed for capillary refill time assessment, given their essentially exploratory nature.;To investigate whether there are differences in macrohemodynamic indicators between intervention and control groups via serial measurements, for 3 days since the randomization, including heart rate, mean arterial pressure, pulse pressure, systolic and diastolic blood pressure, with a significance level of 5% and a 95% confidence interval, respecting the exploratory and descriptive nature of the research, through linear mixed-effects model;To report, in absolute numbers, the incidence of adverse events related to methylene blue in the intervention group.;To describe, in an exploratory way, the variation in Sequential Organ Failure Assessment score-2 (SOFA-2) scale scores during the first 72 hours of patient inclusion in the study, performing comparison between groups through linear mixed-effect | — |
Countries
BR
Contacts
Public ContactBruna Dal Vesco
Centro de Estudos e Pesquisa em Emergências Médicas e Terapia Intensiva - CEPETI
Outcome results
None listed