Methylene Blue in Early Septic Shock

NCT ID: NCT04446871

Last Updated: 2022-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 91 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-17
• Study Completion Date: 2021-01-25

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.

Conditions

Septic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Standard care

Placebo

Group Type: PLACEBO_COMPARATOR

0.9% sodium chloride

Intervention Type: DRUG

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

Methylene blue

Group Type: EXPERIMENTAL

Methylene Blue

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital Civil de Guadalajara

OTHER

Sponsor Role: lead

Responsible Party

Miguel Á Ibarra-Estrada

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Miguel Ibarra-Estrada, MD

Role: PRINCIPAL_INVESTIGATOR

Investigator

Locations

Hospital Civil Fray Antonio Alcalde

Guadalajara, , Mexico

Countries

Mexico

References

Ibarra-Estrada M, Kattan E, Aguilera-Gonzalez P, Sandoval-Plascencia L, Rico-Jauregui U, Gomez-Partida CA, Ortiz-Macias IX, Lopez-Pulgarin JA, Chavez-Pena Q, Mijangos-Mendez JC, Aguirre-Avalos G, Hernandez G. Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial. Crit Care. 2023 Mar 13;27(1):110. doi: 10.1186/s13054-023-04397-7.

Reference Type: DERIVED

PMID: 36915146 (View on PubMed)

Other Identifiers

HCG/CEI-0252/17

Identifier Type: -

Identifier Source: org_study_id