The Effect of Early Use of Methylene Blue on Hemodynamics in Septic Shock

This study will include patients requiring high dose of norepinephrine (NA) to maintain blood pressure after fluid resuscitation. The patients will be randomized into two groups, the study protocol is early combined application of methylene blue. The primary outcome is Sequential Organ Failure Assessment (SOFA) score 72 hours after admission. Second outcome includes duration of shock, length of intensive care unit (ICU) hospitalization and so on. To explore the underlying mechanism, the changes of sublingual microcirculation before and after vasopressor combination will be collected, also is the global longitudinal strain of left ventricle.

Study Overview

• Status: Active, not recruiting
• Conditions: Septic Shock
• Intervention / Treatment: Drug: Methylene Blue

Detailed Description

Background: Decreased vascular tone is one of the main mechanisms leading to septic shock. The guidelines recommend NA as the first-line vasopressor. The benefits of early combination with other vasopressors are not yet known.

Methods:

1. Patients: Septic shock patients in need of high dose of NA (≥0.5ug/kg.min maintaining more than 2 hours) to maintain blood pressure after fluid resuscitation.
2. Intervention: The patients will be randomized into two groups. The study group will receive 2mg/kg methylene blue infusion with 15 minutes, 2 hours laters followed by 0.5mg/kg/h for 4 hours. The control group received conventional treatments, the attending physicians decide the protocol of vasopressors. The data including patients' characters, duration of shock and hospitalization, duration of mechanical ventilation, cumulative dose of vasopressors will be collected. Before and 6h after meeting the inclusion standard, sublingual microcirculation and automated function imaging of myocardium will be performed.
3. Outcome: The primary outcome is SOFA score 72 hours after admission. Second outcome includes duration of shock, length of ICU hospitalization and so on. the changes of sublingual microcirculation will be collected, also is the global longitudinal strain of left ventricle.

• Study Type: Interventional
• Enrollment (Anticipated): 106
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital, Central South University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Septic shock, receive 0.5 ug/kg/min NA to maintain blood pressure for more than 2 hours after fluid resuscitation.

Exclusion Criteria:

• Pregnant women
• Without internal jugular vein or subclavian vein catheterization
• Child-Pugh grade C with liver cirrhosis
• Severe chronic obstructive pulmonary disease (severe acidosis caused by type II respiratory failure, PaCO2 ≥60mmHg and PH<7.2 )
• End-stage of malignant tumors
• Glucose-6-phosphate dehydrogenase (G6PD enzyme) deficiency
• Positive end-respiratory pressure (PEEP) >10mmHg, the oxygenation index <150mmHg under mechanical ventilation
• Definitive pulmonary hypertension or chronic pulmonary heart disease.
• Oral use of 5-hydroxytryptamine in recent 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MB group; This group will be given 2mg/kg methylene blue infusion within 20 minutes, 2 hours later followed by 0.5mg/kg/h for 4 hours.	Drug: Methylene Blue; Once the patient meets inclusion criterial, the interventional group will receive 2mg/kg methylene blue infusion within 20min, followed by 0.5mg/kg/h for 4 hours.
No Intervention: control group; This group will be given conventional vasopressors, except methylene blue, based on the attending doctor's decision.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SOFA score	72 hours after inclusion	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
duration of shock	the duration between diagnosis and relief of septic shock, the latter is defined by stable blood pressure without any vasopressor for 2 hours	2 hours

Collaborators and Investigators

• Sponsor: Xiangya Hospital of Central South University
• Investigators: Principal Investigator: Xiangya Hospital, Central South University, Department of Critical Care Medicine, Xiangya Hospital, Central South University

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2021
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: June 29, 2021
• First Submitted That Met QC Criteria: July 20, 2021
• First Posted (Actual): July 21, 2021

Study Record Updates

• Last Update Posted (Actual): July 21, 2021
• Last Update Submitted That Met QC Criteria: July 20, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: septic shock; methylene blue; vasopressor; refractory shock
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Methylene Blue
• Other Study ID Numbers: 20210621

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The study protocol, objective data could be shared when required.
• IPD Sharing Time Frame: Within 1 year after completion of the study.
• IPD Sharing Access Criteria: Just for academic requirement.
• IPD Sharing Supporting Information Type: Study Protocol; Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No