Efficacy and Safety of Methylene Blue in the Treatment of Severe Septic Shock
- Conditions
- Methylene BlueSepsisSeptic Shock
- Interventions
- Drug: Methylene Blue Intervention GroupDrug: Normal Saline Control Group
- Registration Number
- NCT06481410
- Lead Sponsor
- First Affiliated Hospital of Zhejiang University
- Brief Summary
The goal of this clinical trial is to investigate whether methylene blue injection can safely and effectively improve the survival rate of patients with severe septic shock, shorten the duration of norepinephrine use, reduce the dosage of vasopressors, promptly correct hemodynamics, and improve tissue perfusion and organ function impairment.
- Detailed Description
Researchers will compare methylene blue to a placebo (a look-alike substance that contains no drug) to see if methylene blue works to treat severe septic shock.
Participants will:
Administer a loading dose of 2.5 mg/kg via micro-pump over 15 minutes, followed by a maintenance infusion at a rate of 0.25 mg/kg/hour for 12 hours or until norepinephrine has been continuously discontinued for 4 hours, whichever comes first. If norepinephrine needs to be increased to 0.25 μg/kg/min before the 12-hour period ends, continue using methylene blue until the 12-hour infusion is completed.
Primary Study Endpoint
- 28-day all-cause mortality rate starting from the diagnosis of septic shock.
Secondary Study Endpoints
* Time from the start to the discontinuation of norepinephrine after the diagnosis of septic shock.
* Total dose of norepinephrine used (from enrollment to 72 hours).
* Number of days without norepinephrine within 28 days.
* Duration of mechanical ventilation.
* Rate of CRRT (Continuous Renal Replacement Therapy).
* Length of ICU stay.
* Total hospital stay.
Record the following indicators before methylene blue intervention and at 24 hours, 72 hours, and 5 days after the intervention:
* Highest serum lactate level.
* Lowest mean arterial pressure.
* Alanine aminotransferase (ALT).
* Total bilirubin.
* Creatinine.
* Oxygenation index (P/F ratio).
* Creatine kinase-MB (CK-MB).
* Troponin I (TNI).
* Systemic vascular resistance index (SVRI).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 488
- Age ≥ 18 years.
- Meets the Sepsis 3.0 criteria for septic shock: patients with infection who, despite adequate fluid resuscitation, require vasopressor therapy to maintain a mean arterial pressure (MAP) of ≥ 65 mmHg and have a blood lactate concentration > 2 mmol/L.
- Diagnosed with septic shock and started on norepinephrine within 24 hours.
- Requires a norepinephrine dose of ≥ 0.1 μg/kg/min to maintain a MAP of ≥ 65 mmHg.
- Pregnant or breastfeeding women.
- Individuals allergic to methylene blue or any components of the methylene blue injection.
- Individuals with a personal or family history of glucose-6-phosphate dehydrogenase (G6PD) deficiency.
- Patients with an expected survival time of less than 48 hours.
- Patients who have been on norepinephrine for more than 24 hours.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Methylene Blue Intervention Group Methylene Blue Intervention Group Methylene blue injection, 2.5 mg/kg loading dose over 15 minutes, followed by a continuous infusion of 0.25 mg/kg/hour for 12 hours or until norepinephrine has been continuously discontinued for 4 hours, whichever comes first. Normal Saline Control Group Normal Saline Control Group Normal saline solution, administered in the same manner and duration as the methylene blue intervention.
- Primary Outcome Measures
Name Time Method 28-day survival rate of enrolled patients 28-day Our primary endpoint is the 28-day survival rate of enrolled patients: All enrolled patients will be followed from the time of randomization until 28 days post-enrollment, recording the survival status on the 28th day after enrollment. If a patient dies within 28 days post-enrollment, the number of survival days will be recorded.
Note:
1. Cases where the family requests discharge to home for end-of-life care and the patient subsequently dies will be counted as death cases.
2. Cases where the family requests discharge for non-medical reasons such as financial constraints and no further treatment is sought will be counted as dropout cases.
- Secondary Outcome Measures
Name Time Method The duration and dosage of norepinephrine use 28-day The duration of norepinephrine use：The time from the start of norepinephrine (NE) administration after sepsis diagnosis until its discontinuation. The definition of discontinuation: NE must be stopped for ≥2 hours; if NE is stopped for \<2 hours, it is not considered discontinued. If NE is re-administered after being stopped for more than 2 hours, it is still considered discontinued.
The dosage of norepinephrine use：the total dose of NE used within 72 hours after the patient is enrolled in the study.The duration of mechanical ventilation 28-day The number of days without mechanical ventilation within 28 days post-enrollment. Note: Only full days without mechanical ventilation can be counted as one day.
The duration of overall hospital stay 28-day The duration of overall hospital stay: the total number of days hospitalized starting from the time of patient enrollment in the study. Note: Days hospitalized prior to enrollment are not included.
The duration of ICU stay 28-day ICU length of stay: the number of days in the ICU starting from the time of patient enrollment in the study. Note: Some patients may have multiple ICU admissions; only the ICU stay duration after the current enrollment is recorded.
The safety of methylene blue injection 28-day We will record the complications due to the use of methylene blue, such as hemolysis: We will determine the presence of hemolysis by daily monitoring of urine color, red blood cells, hemoglobin count in complete blood count, and bilirubin levels in liver function tests. If the patient's urine turns dark brown (similar to soy sauce), accompanied by a decrease in hemoglobin and red blood cell count and a simultaneous increase in bilirubin, hemolysis will be considered.
Trial Locations
- Locations (1)
The First Affiliated Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China