Low Dose Versus High Dose Methylene Blue in Septic Patients

Septic Shock Clinical Trial

Official title:

Comparative Study Between High and Low Dose Methylene Blue Infusion in Septic Cancer Patients. A Randomized Blinded Controlled Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06005558
• Other study ID #: Methylene blue
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: August 1, 2023
• Est. completion date: March 15, 2024

Study information

• Verified date: February 2024
• Source: National Cancer Institute, Egypt
• Contact: Ehab H Shaker, MD
• Phone: 01222438820
• Email: ehabhanafy2006[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main aim of this study is to examine the various effects of continuous methylene blue infusion in septic cancer patients and to compare it with the traditional infusion of noradrenaline in such patients .

Description:

Exaggerated host response to infection, may result in sepsis, which is life-threatening organ dysfunction . Though considered the number one cause of in-hospital deaths , it can be treatable with early prompt interventions.

The 2021 SSC Guidelines use the Third International Consensus definitions, also known as Sepsis-3. Where sepsis is defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection." Organ dysfunction is evidenced by an increased score of 2 or more in the Quick Sequential [Sepsis-related] Organ Failure Assessment (QSOFA), and septic shock is considered as "a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone." To diagnose septic shock, an euvolemic patient must require vasopressor support to achieve a mean arterial pressure of at least 65 mm Hg and have a lactate level above 2 mmol/L.

The triad of intravenous fluid, vasopressors and antibiotics in the first hour is the mainstay of septic shock management. Aim of management is to maintain patient hemodynamically stable until antibiotics kick in and fight infection. In case of non-responders, low dose corticosteroids are prescribed. Other drugs need to be studied to also help in cases of non-responders and to improve outcome in general. Methylene blue (MB) is a nitric oxide inhibitor that can counteract the vasodilatation in early septic shock.

Nitric oxide (NO) activates soluble guanylyl cyclase (sGC) which activates cyclic guanosine monophosphate (cGMP)-dependent protein kinases (PKGs) that cause vasodilatation. Methylene blue selectively blocks sGC and inhibits iNOS. Therefore, it selectively acts on the microcirculation.

Onset of action of intravenous MB is 30-60 min. Peak concentration at 30 min. It is excreted through bile and fecal routes plus through the kidneys. Due to the short Plasma half-life of 5-6 hours, some studies used continuous infusion of 0.25-2 mg/kg/h, for up to 3 days following the initial bolus dose

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: March 15, 2024
• Est. primary completion date: February 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Patients aged = 18 years and = 65 with septic shock as defined by Sepsis-3 criteria (confirmed infection, requiring vasopressor to maintain a mean arterial blood pressure (MAP) = 65 mmHg, and serum lactate > 2 mmol/L after adequate fluid resuscitation), and requiring mechanical ventilation.

Exclusion Criteria:

• myocardial infarction or cerebrovascular accident within the last 3 months.

• severe lung , liver or kidney disease (creatinine >3.5 mg/dL).

• pregnancy.

• glucose 6-phosphate-dehydrogenase deficiency.

• known allergy to MB or food dyes and the use of nitrates within the last 3 days.

• more than 24 hrs since initiation of norepinephrine.

• other causes of shock than sepsis .

• recent intake (4-weeks) of selective serotonin re-uptake inhibitors or MAOi.

• refusal of the patient guardian to participate.

Related Conditions & MeSH terms

• Septic Shock
• Shock, Septic

Intervention

Drug:
• Normal saline
100 ml 0.9% Nacl over 20 minutes, followed by continuous infusion of normal saline for 72 hours.
• Methylene Blue low dose
A bolus of MB 1mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.
• Methylene Blue high dose
A bolus of MB 4mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.

Locations

Country	Name	City	State
Egypt	National Cancer Institute	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute, Egypt

Country where clinical trial is conducted

Egypt, 

References & Publications (1)

Chalise SN, Sahib TA, Boyer GA, Pathak V. Methylene Blue in Refractory Shock. Cureus. 2022 Nov 6;14(11):e31158. doi: 10.7759/cureus.31158. eCollection 2022 Nov. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Discontinuation of vasopressor	Time for noradrenaline discontinuation	7 days
Secondary	Mortality	Number of deaths	28 days