Efficacy and Safety of Methylene Blue in the Treatment of Severe Septic Shock

Zhejiang University

Status: Enrolling

Conditions: Methylene Blue; Septic Shock; Sepsis

Treatments: Drug: Methylene Blue Intervention Group; Drug: Normal Saline Control Group

Study type: Interventional

Funder types: Other

Identifiers

NCT06481410

2024-051

Details and patient eligibility

About

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.

Full 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).

Enrollment: 488 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

488 participants in 2 patient groups, including a placebo group

Methylene Blue Intervention Group

Experimental group

Description:

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.

Treatment:

Drug: Methylene Blue Intervention Group

Normal Saline Control Group

Placebo Comparator group

Description:

Normal saline solution, administered in the same manner and duration as the methylene blue intervention.

Treatment:

Drug: Normal Saline Control Group