Septic ShockNCT06481410
Efficacy and Safety of Methylene Blue in the Treatment of Severe Septic Shock
A study testing Methylene Blue Intervention Group in people with Septic Shock and Methylene Blue, run by First Affiliated Hospital of Zhejiang University at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Septic Shock, Methylene Blue, Sepsis
- What is being tested?
- Methylene Blue Intervention Group
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 488 participants
- Where
- 1 siteChina
- Study dates
- 22 Jun 2024to 31 Dec 2027
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang
Wenqiao Yu, PhD
About this study
Official title: Exploratory Study on the Efficacy and Safety of Methylene Blue in Treating Severe Septic Shock Patients: A Prospective, Randomized, Controlled Trial
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.
Read the 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).
- Conditions
- Septic Shock, Methylene Blue, Sepsis
- Being tested
- Methylene Blue Intervention Group, Normal Saline Control Group
- Keywords
- Septic Shock, Methylene blue, Sepsis
- Medical subject headings
- Shock, Septic, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylene Blue Intervention GroupDrug
In addition to standard treatment, patients will receive methylene blue intervention. The method is as follows: a loading dose of 2.5 mg/kg administered via micro-pump over 15 minutes, followed by a continuous 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 0.1 μg/kg/min before the 12-hour period ends, continue using methylene blue until the 12-hour infusion is completed.
Normal Saline Control GroupDrug
In addition to standard treatment, patients will receive a placebo control with normal saline, administered for the same duration as the intervention group.
| Study group | Role | What they receive |
|---|---|---|
| Methylene Blue Intervention Group | Experimental | 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. Receives: Drug: Methylene Blue Intervention Group |
| Normal Saline Control Group | Placebo comparator | Normal saline solution, administered in the same manner and duration as the methylene blue intervention. Receives: Drug: Normal Saline Control Group |
What is being measured
The primary outcome is the main question the study is designed to answer.
28-day survival rate of enrolled patients
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:
- Cases where the family requests discharge to home for end-of-life care and the patient subsequently dies will be counted as death cases.
- 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.
Measured: 28-day
Secondary outcomes (5)
The duration and dosage of norepinephrine use
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.
Measured: 28-day
The duration of mechanical ventilation
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.
Measured: 28-day
The duration of ICU stay
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.
Measured: 28-day
The duration of overall hospital stay
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.
Measured: 28-day
The safety of methylene blue injection
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.
Measured: 28-day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2024
- Study start22 Jun 2024
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a prospective, randomized, controlled, single-blind study.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 488 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Zhejiang University
- Sponsor type
- University, hospital or other
- Collaborators
- Yuyao People's Hospital, Taizhou Enze Medical Center Group, Ningbo Medical Center Lihuili Hospital, Nanning Second People's Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06481410
- Sponsor's protocol ID
- 2024-051
- Status last verified
- Oct 2026
- First submitted
- 21 Jun 2024
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: You can explain the reason and contact the study initiator via email to request the data. The email address is:yuwenqiao1980@zju.edu.cn