NCT06005558

Low Dose Versus High Dose Methylene Blue in Septic Patients

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

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 90 (actual)
• Sponsor: National Cancer Institute, Egypt · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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 .

Detailed 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

Conditions

• Septic Shock

Interventions

Type	Name	Description
DRUG	Normal saline	100 ml 0.9% Nacl over 20 minutes, followed by continuous infusion of normal saline for 72 hours.
DRUG	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.
DRUG	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.

Timeline

• Start date: 2023-08-01
• Primary completion: 2024-04-29
• Completion: 2024-05-15
• First posted: 2023-08-22
• Last updated: 2024-07-05

Locations

1 site across 1 country: Egypt