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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
50
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.
Irmandade da Santa Casa de Misericórdia de Curitiba
Curitiba, Paraná, Brazil
RECRUITINGTo 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.
Time frame: 28 days after randomization.
Capillary refill time
Serial capillary refill time from randomization up to 72 hours later.
Time frame: 72 hours after randomization.
Serum lactate level
Serial measurements of serum lactate level during the 72 hours after randomization.
Time frame: 72 hours after randomization.
Arteriovenous carbon dioxide difference (gapCO2)
Serial measurements of arteriovenous carbon dioxide difference (gapCO2) during 72h after randomization.
Time frame: 72h after randomization.
Central venous oxygen saturation (SvO2)
Serial measurements of central venous oxygen saturation (SvO2) during 72h after randomization.
Time frame: 72h after randomization.
Serial measurements of heart rate
Serial measurements of heart rate from randomization up to 72 hours later.
Time frame: 72 hours after randomization.
Serial measurements of mean arterial pressure
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Serial measurements of mean arterial pressure from randomization up to 72 hours later.
Time frame: 72 hours after randomization.
Serial measurements of pulse pressure
Serial measurements of pulse pressure from randomization up to 72 hours later.
Time frame: 72 hours after randomization.
Serial measurements of systolic arterial pressure
Serial measurements of systolic arterial pressure from randomization up to 72 hours later.
Time frame: 72 hours after randomization.
Serial measurements of dyastolic arterial pressure
Serial measurements of dyastolic arterial pressure from randomization up to 72 hours later.
Time frame: 72 hours after randomization.
Methylene blue-related adverse events
Incidence of adverse events during the three days of administration of methylene blue and up to 28 days after.
Time frame: 28 days after randomization.