Clinical trial NCT06481410: Efficacy and Safety of Methylene Blue in the Treatment of Severe Septic Shock
Official title: Exploratory Study on the Efficacy and Safety of Methylene Blue in Treating Severe Septic Shock Patients: A Prospective, Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Septic Shock
Methylene Blue
Sepsis
Keywords: Septic Shock
Methylene blue
Sepsis
Lead sponsor: First Affiliated Hospital of Zhejiang University
Sponsor class: OTHER
Collaborators: name: Yuyao People's Hospital
name: Taizhou Enze Medical Center Group
name: NINGBO MEDICAL CENTER LIHUIIHOSPITAI
name: People's Hospital of Guangxi Zhuang Autonomous Region
name: The second Nanning People's Hospital
name: GUI LIN PEOPLE'S HOSPITAL
name: Guangxi Hospital Division of The First Affiliated Hospital, Sun Yat-sen University
name: The First People's Hospital of Huzhou
name: Hangzhou Yuhang District Second People's Hospital
name: Wuming Hospital of Guangxi Medical University
First posted: 2024-07-01
Enrollment: 488
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a prospective, randomized, controlled, single-blind study.
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years.
2. 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.
3. Diagnosed with septic shock and started on norepinephrine within 24 hours.
4. Requires a norepinephrine dose of ≥ 0.1 μg/kg/min to maintain a MAP of ≥ 65 mmHg.

Exclusion Criteria:

1. Pregnant or breastfeeding women.
2. Individuals allergic to methylene blue or any components of the methylene blue injection.
3. Individuals with a personal or family history of glucose-6-phosphate dehydrogenase (G6PD) deficiency.
4. Patients with an expected survival time of less than 48 hours.
5. Patients who have been on norepinephrine for more than 24 hours.

Primary outcomes:
measure: 28-day survival rate of enrolled patients
timeFrame: 28-day
Secondary outcomes:
measure: The duration and dosage of norepinephrine use
timeFrame: 28-day
measure: The duration of mechanical ventilation
timeFrame: 28-day
measure: The duration of ICU stay
timeFrame: 28-day
measure: The duration of overall hospital stay
timeFrame: 28-day
measure: The safety of methylene blue injection
timeFrame: 28-day
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References: