Septic ShockPhase 2/3NCT07264543
Early Methylene Blue in the Microhemodynamics of Septic Patients
A Phase 2/3 study testing Methylene blue infusion in people with Septic Shock and Hypoperfusion, run by Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva at 1 site in Brazil.
Trial summary
The aim of the study is to evaluate the viability and feasibility of its protocol in order to conduct a larger clinical trial to assess whether methylene blue can improve patient-centered clinical outcomes such as mortality or length of hospital stay in septic shock patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock, Hypoperfusion
- What is being tested?
- Methylene blue infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteBrazil
- Study dates
- 9 Jan 2026to 31 Dec 2026
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients with a diagnosis of sepsis and persistent hemodynamic dysfunction despite adequate fluid resuscitation, requiring escalation of noradrenaline dose to maintain mean arterial pressure ≥65 mmHg, with prolonged capillary refill time or septic shock according to Sepsis-3 definition, within less than 6 hours of the diagnosis, will be eligible for the study.
Who cannot join
- Pregnant or breastfeeding patients;
- Patients with any withdrawal or withholding life-sustaining intervention;
- Cardiac surgery patients in the immediate postoperative period;
- Refractory septic shock, with a high propability of death within 24 hours;
- Personal or familiar history of glucose-6-phosphate dehydrogenase (G6PD) deficiency;
- Allergy to methylene blue, phenothiazines, or food dyes;
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- Recent administration of linezolid (less than 14 days ago);
- Recent intake of serotonergic psychiatric medications (less than 2 weeks ago - with the exception of fluoxetine, which must be less than 5 weeks ago),
- Recent intake (less than 2 weeks ago) of monoamine oxidase inhibitors (MAOIs), such as rasagiline and selegiline.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site, 1 recruiting
- Recruiting
Irmandade da Santa Casa de Misericórdia de Curitiba
Curitiba, Paraná, 80010-030
Bruna Dal Vesco, +55 (41) 3362-6633, brunadalvesco@gmail.com
About this study
Official title: Evaluation of Early Methylene Blue in the Microhemodynamics of Septic Patients: a Feasibility Randomized Controlled Trial
The aim of the study is to evaluate the viability and feasibility of its protocol in order to conduct a larger clinical trial to assess whether methylene blue can improve patient-centered clinical outcomes such as mortality or length of hospital stay in septic shock patients.
Read the detailed description
One of the primary causes of high mortality in patients with septic shock is microcirculatory dysfunction related to vasodilation caused by excessive oxide nitric production. It has been shown that methylene blue, an old and safe drug that can reduce vasodilation by blocking nitric oxide pathways, is a vasopressor-sparing treatment in sepsis. Nevertheless, there is no evidence that methylene blue improves patient-centered clinical outcomes such as mortality. Understanding how early methylene blue affects the microhemodynamics of septic shock patients may lead to relevant clinical results that can improve their prognosis. So, the objective of the study is to evaluate the viability and feasibility of the study protocol for a larger clinical trial, assessing the effectiveness of early methylene blue in the microhemodynamics of septic shock patients, mainly through the capillary refill time measurement. For this purpose, a pilot study of an open-label, randomized, controlled and single-center clinical trial will be conducted, with two treatment arms: the intervention group (methylene blue plus standard treatment) and the control group (standard treatment). Fifty adult patients with septic shock within the first six hours of diagnosis will be included in this study. They will be randomized to either receive a methylene blue infusion or not. The randomization will be conducted using RedCap with a 1:1 ratio and variable block sizes. The primary outcome will be to assess the feasibility, which is defined as completing the study recruitment within the 12-month timeline and achieving protocol adherence of 90% or higher. Comparisons between groups for serially measured micro and macrohemodynamics parameters will be the secondary outcomes. Additionally, the incidence of adverse events related to methylene blue will be monitored.
- Conditions
- Septic Shock, Hypoperfusion
- Being tested
- Methylene blue infusion
- Keywords
- Septic Shock, Methylene Blue, Microcirculation, Capillary Refill Time
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylene blue infusionDrug
Also called Methylene blue, Phenothiazines
Methylene blue at a dose of 100mg (diluted in 100ml of 5% dextrose solution) in continuous infusion for 06 hours per day, for 03 days, plus standard treatment according to international guidelines for the management of sepsis and septic shock. The 03 consecutive MB infusions, each lasting 06 hours, will be performed every 24 hours, starting from randomization: the first infusion at T0, the second at T24, and the third at T48, considering T0 the moment after the patient randomization into the study.
The interruption of the protocol will be recommended if vasopressors are completely discontinued during the three days of methylene blue infusion. The attending physician may discontinue methylene blue treatment if judges necessary. Similarly, interruption may occur if the family or patient request.
| Study group | Role | What they receive |
|---|---|---|
| Methylene blue group | Experimental | The intervention group will receive methylene blue plus standard treatment for septic shock, according to the international guidelines. Receives: Drug: Methylene blue infusion |
| Control group | No intervention | The control group will receive the standard treatment according to international guidelines for the management of sepsis and septic shock. |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the feasibility of the study protocol.
The primary outcome of the study is to evaluate feasibility, defined as completing the study protocol according to the planned timeline and with 90% or more protocol adherence. Protocol adherence will be defined as the use of the allocated therapy in the intervention group for 6 hours for 3 days (or interruption of methylene blue if the patient does not require a vasoactive drug anymore). Justified interruptions will not be considered violations.
Measured: 28 days after randomization.
Secondary outcomes (10)
Capillary refill time
Serial capillary refill time from randomization up to 72 hours later.
Measured: 72 hours after randomization.
Serum lactate level
Serial measurements of serum lactate level during the 72 hours after randomization.
Measured: 72 hours after randomization.
Arteriovenous carbon dioxide difference (gapCO2)
Serial measurements of arteriovenous carbon dioxide difference (gapCO2) during 72h after randomization.
Measured: 72h after randomization.
Central venous oxygen saturation (SvO2)
Serial measurements of central venous oxygen saturation (SvO2) during 72h after randomization.
Measured: 72h after randomization.
Serial measurements of heart rate
Serial measurements of heart rate from randomization up to 72 hours later.
Measured: 72 hours after randomization.
Serial measurements of mean arterial pressure
Serial measurements of mean arterial pressure from randomization up to 72 hours later.
Measured: 72 hours after randomization.
Serial measurements of pulse pressure
Serial measurements of pulse pressure from randomization up to 72 hours later.
Measured: 72 hours after randomization.
Serial measurements of systolic arterial pressure
Serial measurements of systolic arterial pressure from randomization up to 72 hours later.
Measured: 72 hours after randomization.
Serial measurements of dyastolic arterial pressure
Serial measurements of dyastolic arterial pressure from randomization up to 72 hours later.
Measured: 72 hours after randomization.
Methylene blue-related adverse events
Incidence of adverse events during the three days of administration of methylene blue and up to 28 days after.
Measured: 28 days after randomization.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2025
- Study start9 Jan 2026
- Primary completion30 Nov 2026 (estimated)
- Study completion31 Dec 2026 (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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva
- Sponsor type
- University, hospital or other
- Collaborators
- Irmandade da Santa Casa de Misericordia de Curitiba
- Responsible party
- Principal investigator, Bruna Cassia Dal Vesco, Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva
- Investigators
- Álvaro Réa-Neto, Study chair, CEPETI - Centro de Estudos e Pesquisa em Emergências Médicas e Terapia Intensiva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07264543
- Sponsor's protocol ID
- U1111-1331-7627
- Other IDs
- Approval number 7.955.174, CAAE 93099325.5.0000.0020
- Status last verified
- Mar 2026
- First submitted
- 21 Nov 2025
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Early Methylene Blue in the Microhemodynamics of Septic Patients: a Feasibility Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07264543
- Acronym / sponsor ID
- U1111-1331-7627
- Conditions
- Septic Shock, Hypoperfusion
- Keywords
- Septic Shock, Methylene Blue, Microcirculation, Capillary Refill Time
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia IntensivaUniversity, hospital or other
- Collaborators
- Irmandade da Santa Casa de Misericordia de Curitiba
- Study start
- 9 Jan 2026 (actual)
- Primary completion
- 30 Nov 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 4 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to evaluate the viability and feasibility of its protocol in order to conduct a larger clinical trial to assess whether methylene blue can improve patient-centered clinical outcomes such as mortality or length of hospital stay in septic shock patients.
Detailed description
One of the primary causes of high mortality in patients with septic shock is microcirculatory dysfunction related to vasodilation caused by excessive oxide nitric production. It has been shown that methylene blue, an old and safe drug that can reduce vasodilation by blocking nitric oxide pathways, is a vasopressor-sparing treatment in sepsis. Nevertheless, there is no evidence that methylene blue improves patient-centered clinical outcomes such as mortality. Understanding how early methylene blue affects the microhemodynamics of septic shock patients may lead to relevant clinical results that can improve their prognosis. So, the objective of the study is to evaluate the viability and feasibility of the study protocol for a larger clinical trial, assessing the effectiveness of early methylene blue in the microhemodynamics of septic shock patients, mainly through the capillary refill time measurement. For this purpose, a pilot study of an open-label, randomized, controlled and single-center clinical trial will be conducted, with two treatment arms: the intervention group (methylene blue plus standard treatment) and the control group (standard treatment). Fifty adult patients with septic shock within the first six hours of diagnosis will be included in this study. They will be randomized to either receive a methylene blue infusion or not. The randomization will be conducted using RedCap with a 1:1 ratio and variable block sizes. The primary outcome will be to assess the feasibility, which is defined as completing the study recruitment within the 12-month timeline and achieving protocol adherence of 90% or higher. Comparisons between groups for serially measured micro and macrohemodynamics parameters will be the secondary outcomes. Additionally, the incidence of adverse events related to methylene blue will be monitored.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methylene blue group | Experimental | Drug: Methylene blue infusionThe intervention group will receive methylene blue plus standard treatment for septic shock, according to the international guidelines. |
| Control group | No intervention | –The control group will receive the standard treatment according to international guidelines for the management of sepsis and septic shock. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Adult patients with a diagnosis of sepsis and persistent hemodynamic dysfunction despite adequate fluid resuscitation, requiring escalation of noradrenaline dose to maintain mean arterial pressure ≥65 mmHg, with prolonged capillary refill time or septic shock according to Sepsis-3 definition, within less than 6 hours of the diagnosis, will be eligible for the study.
Key exclusion criteria (9 listed)
- Pregnant or breastfeeding patients;
- Patients with any withdrawal or withholding life-sustaining intervention;
- Cardiac surgery patients in the immediate postoperative period;
- Refractory septic shock, with a high propability of death within 24 hours;
- Personal or familiar history of glucose-6-phosphate dehydrogenase (G6PD) deficiency;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methylene blue infusionAlso: Methylene blue, PhenothiazinesMethylene blue at a dose of 100mg (diluted in 100ml of 5% dextrose solution) in continuous infusion for 06 hours per day, for 03 days, plus standard treatment according to international guidelines for the management of sepsis and septic shock. The 03 consecutive MB infusions, each lasting 06 hours, will be performed every 24 hours, starting from randomization: the first infusion at T0, the second at T24, and the third at T48, considering T0 the moment after the patient randomization into the study. The interruption of the protocol will be recommended if vasopressors are completely discontinued during the three days of methylene blue infusion. The attending physician may discontinue methylene blue treatment if judges necessary. Similarly, interruption may occur if the family or patient request. | Drug | Methylene blue group |
Primary outcome
To evaluate the feasibility of the study protocol.
Time frame: 28 days after randomization.
The primary outcome of the study is to evaluate feasibility, defined as completing the study protocol according to the planned timeline and with 90% or more protocol adherence. Protocol adherence will be defined as the use of the allocated therapy in the intervention group for 6 hours for 3 days (or interruption of methylene blue if the patient does not require a vasoactive drug anymore). Justified interruptions will not be considered violations.
10 secondary outcomes
Capillary refill time
Time frame: 72 hours after randomization.
Serum lactate level
Time frame: 72 hours after randomization.
Arteriovenous carbon dioxide difference (gapCO2)
Time frame: 72h after randomization.
Central venous oxygen saturation (SvO2)
Time frame: 72h after randomization.
Serial measurements of heart rate
Time frame: 72 hours after randomization.
Serial measurements of mean arterial pressure
Time frame: 72 hours after randomization.
Serial measurements of pulse pressure
Time frame: 72 hours after randomization.
Serial measurements of systolic arterial pressure
Time frame: 72 hours after randomization.
Serial measurements of dyastolic arterial pressure
Time frame: 72 hours after randomization.
Methylene blue-related adverse events
Time frame: 28 days after randomization.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
- Individual participant dataSharing planned: No
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Sepsis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Álvaro Réa-Neto study chair
CEPETI - Centro de Estudos e Pesquisa em Emergências Médicas e Terapia Intensiva
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Methylene blue infusion in people with Septic Shock and Hypoperfusion, run by Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Bruna Dal Vesco (+55 (41) 3362-6633, brunadalvesco@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the feasibility of the study protocol. (time frame: 28 days after randomization.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2026.