Methylene Blue in Early Septic Shock

Septic Shock Clinical Trial

— SHOCKEM-Blue  

Official title:

Early Use of Methylene Blue in Patients With Septic Shock: a Pilot Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04446871
• Other study ID #: HCG/CEI-0252/17
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: March 17, 2017
• Est. completion date: January 25, 2021

Study information

• Verified date: November 2022
• Source: Hospital Civil de Guadalajara
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: January 25, 2021
• Est. primary completion date: December 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Septic Shock
• Shock
• Shock, Septic

Intervention

Drug:
• 0.9% sodium chloride
Intravenous infusion of 500 cc of 0.9% sodium chloride solution for 6 h, once a day for a total of 3 doses.
• Methylene Blue
Intravenous infusion of 100 mg methylene blue in 500 cc of 0.9% sodium chloride solution for 6 h, once a day for a total of 3 doses.

Locations

Country	Name	City	State
Mexico	Hospital Civil Fray Antonio Alcalde	Guadalajara

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Civil de Guadalajara

Country where clinical trial is conducted

Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in pulmonary function after treatment	Change in P/F index after three doses of methylene blue	7 days
Primary	Vasopressor requirement	Total time to shock resolution (hours)	28 days
Secondary	Time to lactate normalization	Time in hours until lactate is <2 mmol/L	7 days
Secondary	Length of stay in intensive care unit	Time in days until ICU discharge	28 days
Secondary	Intensive care unit mortality	Mortality in intensive care unit	28 days