Clinical trial NCT04446871: Methylene Blue in Early Septic Shock
Official title: Early Use of Methylene Blue in Patients With Septic Shock: a Pilot Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Septic Shock
Keywords: Septic shock
Methylene blue
Norepinephrine
Lead sponsor: Hospital Civil de Guadalajara
Sponsor class: OTHER
First posted: 2020-06-25
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Septic shock is a subset of sepsis characterized by a decrease in vascular tone, which contributes to impaired regional blood flow distribution, and leads to organic failure. Besides intravenous fluids and adequate antimicrobial therapy, patients with septic shock require vasopressor support, which can lead to many adverse effects, therefore, non-vasopressor agents that can improve hemodynamic status are needed. In this randomized controlled-study, the investigators will address the efficacy and safety of infusion with methylene blue in patients with septic shock.

Detailed description: Unlike sepsis, septic shock mortality is not declining for the last decade, and is still around 40%. After restoring intravascular volume, many patients need vasopressor agents to maintain arterial blood pressure, which leads to improvement of perfusion at some vascular beds, however some organs may suffer from maldistribution of blood flow. These changes of regional blood flow may compromise oxygen delivery and perpetuate the inflammation and tissue damage associated with the state of shock.

One of the main mechanisms of vasodilation after inflammatory insults, is the activation of the inducible isoform of Nitric Oxide Synthase (iNOS), and the subsequent increase in the levels of nitric oxide, which even reduces the response to vasoconstrictor agents. Methylene blue (MB) is a selective inhibitor of iNOS, which has been used successfully in patients with post-cardiopulmonary bypass associated vasoplegia, however, the evidence of the use of MB in septic shock patients is limited to case reports, observational and small studies. In this randomized controlled trial, the investigators will compare the efficacy and safety outcomes of repeated doses of MB in patients with septic shock.

Eligibility criteria: Inclusion Criteria:

* Septic shock diagnosis, according to the Sepsis-3 consensus.
* Prior adequate fluid resuscitation according to dynamic predictors of volume responsiveness.
* More than 6 h and less than 24 h of norepinephrine requirement to maintain a mean arterial pressure ≥65 mmHg.

Exclusion Criteria:

* Age \< 18 years.
* Pregnancy.
* Not expected to survive 48 hours.
* Presence or high suspicion of concurrent hemorrhagic, obstructive or hypovolemic shock.
* Personal or familiar history of glucose-6-phosphate dehydrogenase deficiency.
* Allergic to methylene blue, phenothiazines, or food dyes.
* Recent intake (4-weeks) of selective serotonin re-uptake inhibitors.
* Refusal of the patient or decision maker to enroll in the study.

Primary outcomes:
measure: Vasopressor requirement
timeFrame: 28 days
Secondary outcomes:
measure: Time to lactate normalization
timeFrame: 7 days
measure: Length of stay in intensive care unit
timeFrame: 28 days
measure: Intensive care unit mortality
timeFrame: 28 days
Other outcomes:
measure: Change in pulmonary function after treatment
timeFrame: 7 days
Locations:
city: Guadalajara
country: Mexico
facility: Hospital Civil Fray Antonio Alcalde
Study officials:
affiliation: Investigator
name: Miguel Ibarra-Estrada, MD
role: PRINCIPAL_INVESTIGATOR
References: