Acute Kidney InjuryPhase 2BLUENCT05092165
Methylene Blue for the Prevention of Hypotension During Hemodialysis
A Phase 2 study testing Methylene Blue in people with Acute Kidney Injury and Shock, run by Federal University of São Paulo at 1 site in Brazil.
Trial summary
Hypotension is a common complication of intermittent renal replacement therapy. Methylene blue, an inhibitor of nitric oxide synthesis, has been suggested to improve hemodynamics during renal replacement therapy in ambulatory patients, but evidence is lacking for critically ill patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Kidney Injury, Shock, Intradialytic Hypotension
- What is being tested?
- Methylene Blue
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 261 participants
- Where
- 1 siteBrazil
- Study dates
- 21 Oct 2021to 16 Dec 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Patients over 18 years old
- Acute kidney injury or acute-on-chronic kidney disease requiring intermittent renal replacement therapy hemodialysis
- Systolic blood pressure lower than 100 mmHg or use of vasopressor
- Signed informed consent
Who cannot join
- Pregnancy
- Life expectancy less than 24 hours
- Exclusive palliative or end-of-life care
- RRT due to hypertensive crisis
- Known allergy to methylene blue
- Known Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Show all 9Show fewer
- Prior participation in the study
- Acute coronary syndrome
- Chronic nitrate oral use
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prospective, Randomized, Controlled Trial Assessing the Effects of Methylene Blue for the Prevention of Hypotension During Renal Replacement Therapy
Hypotension is a common complication of intermittent renal replacement therapy. Methylene blue, an inhibitor of nitric oxide synthesis, has been suggested to improve hemodynamics during renal replacement therapy in ambulatory patients, but evidence is lacking for critically ill patients.
This trial will assess whether methylene blue can improve hemodynamics and blood pressure for patients with shock requiring renal replacement therapy.
Read the detailed description
BLUE is a randomized, multicenter, open-label trial. Patients with high risk of hypotension during RRT will be randomized to receive either methylene blue infusion at a dose of 1 mg/kg as a bolus, followed by continuous infusion of 0.1 mg/kg of body weight in a total of 200 mL of saline solution throughout the dialysis session, or to usual care. The usual care group will not receive any intervention. A total of 260 patients are expected to be randomized in a 1:1 ratio.
- Conditions
- Acute Kidney Injury, Shock, Intradialytic Hypotension, Intradialytic Hypertension in Hemodialysis Patients
- Being tested
- Methylene Blue, Control
- Keywords
- methylene blue, intradialytic hypotension, hemodialysis
- Medical subject headings
- Acute Kidney Injury, Shock
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylene BlueDrug
BLUE group will receive an intravenous infusion of methylene blue. Following a previous study(12), 1 mg/kg of methylene blue 2% diluted in 50 mL of saline solution will be administered as a bolus over 5 minutes, followed by a continuous infusion of 0.1 mg/kg body weight in a total of 250 mL of saline solution throughout the RRT session
ControlOther
Usual care during renal replacement therapy
| Study group | Role | What they receive |
|---|---|---|
| Methylene Blue | Active comparator | Methylene blue will be infused during renal replacement therapy Receives: Drug: Methylene Blue |
| Control | Other | usual care Receives: Other: Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite Endpoint
The primary outcome will be a composite consisting of any of the following events: (1) initiation of vasopressor therapy or an increase in vasopressor dose by at least 20% from baseline; (2) interruption of the RRT session; (3) interruption of fluid removal at the request of the attending physician at any point during the session.
Measured: 6 hours
Secondary outcomes (7)
Hypotension
Mean blood pressure below 65 mmHg for at least 5 minutes during renal replacement therapy
Measured: 6 hours
Maximum vasopressor dose
Maximum vasopressor dose, in micro-grams per kilogram per minute used during de first 24 hours
Measured: 24 hours
Norepinephrine equivalent dose (NEE)
The cumulative norepinephrine equivalent dose (NEE)
Measured: 24 hours
RRT session fluid balance
The fluid balance of RTT session
Measured: 24 hours
24-hour fluid balance
The fluid balance on 24-hour after RTT session
Measured: 24 hours
Mortality in the intensive care unit
Death in the intensive care unit
Measured: 60 days
Mortality in the hospital
Death during hospital stay
Measured: 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2021
- Study start21 Oct 2021
- Primary completion16 Dec 2025
- Study completion16 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Kidney InjuryStudies 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 261 participants (actual)
Sponsor and investigators
- Lead sponsor
- Federal University of São Paulo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Flavia Ribeiro Machado, Federal University of São Paulo
- Investigators
- Carla Pontes, MD, Principal investigator, Federal University of São PauloFlavia R Machado, MD, PhD, Study chair, Federal University of São Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05092165
- Sponsor's protocol ID
- BLUE
- Acronym
- BLUE
- Status last verified
- Oct 2025
- First submitted
- 13 Oct 2021
- Last updated
- 17 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be shared upon reasonable request
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Randomized, Controlled Trial Assessing the Effects of Methylene Blue for the Prevention of Hypotension During Renal Replacement Therapy
- ClinicalTrials.gov ID
- NCT05092165
- Acronym / sponsor ID
- BLUE / BLUE
- Conditions
- Acute Kidney Injury, Shock, Intradialytic Hypotension, Intradialytic Hypertension in Hemodialysis Patients
- Keywords
- methylene blue, intradialytic hypotension, hemodialysis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 261 participants (actual)
- Lead sponsor
- Federal University of São PauloUniversity, hospital or other
- Study start
- 21 Oct 2021 (actual)
- Primary completion
- 16 Dec 2025 (actual)
- Study completion
- 16 Dec 2025 (actual)
- First posted
- 25 Oct 2021 (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.
Hypotension is a common complication of intermittent renal replacement therapy. Methylene blue, an inhibitor of nitric oxide synthesis, has been suggested to improve hemodynamics during renal replacement therapy in ambulatory patients, but evidence is lacking for critically ill patients.
This trial will assess whether methylene blue can improve hemodynamics and blood pressure for patients with shock requiring renal replacement therapy.
Detailed description
BLUE is a randomized, multicenter, open-label trial. Patients with high risk of hypotension during RRT will be randomized to receive either methylene blue infusion at a dose of 1 mg/kg as a bolus, followed by continuous infusion of 0.1 mg/kg of body weight in a total of 200 mL of saline solution throughout the dialysis session, or to usual care. The usual care group will not receive any intervention. A total of 260 patients are expected to be randomized in a 1:1 ratio.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methylene Blue | Active comparator | Drug: Methylene BlueMethylene blue will be infused during renal replacement therapy |
| Control | Other | Other: Controlusual care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients over 18 years old
- Acute kidney injury or acute-on-chronic kidney disease requiring intermittent renal replacement therapy hemodialysis
- Systolic blood pressure lower than 100 mmHg or use of vasopressor
- Signed informed consent
Key exclusion criteria (9 listed)
- Pregnancy
- Life expectancy less than 24 hours
- Exclusive palliative or end-of-life care
- RRT due to hypertensive crisis
- Known allergy to methylene blue
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 BlueBLUE group will receive an intravenous infusion of methylene blue. Following a previous study(12), 1 mg/kg of methylene blue 2% diluted in 50 mL of saline solution will be administered as a bolus over 5 minutes, followed by a continuous infusion of 0.1 mg/kg body weight in a total of 250 mL of saline solution throughout the RRT session | Drug | Methylene Blue |
| ControlUsual care during renal replacement therapy | Other | Control |
Primary outcome
Composite Endpoint
Time frame: 6 hours
The primary outcome will be a composite consisting of any of the following events: (1) initiation of vasopressor therapy or an increase in vasopressor dose by at least 20% from baseline; (2) interruption of the RRT session; (3) interruption of fluid removal at the request of the attending physician at any point during the session.
7 secondary outcomes
Hypotension
Time frame: 6 hours
Maximum vasopressor dose
Time frame: 24 hours
Norepinephrine equivalent dose (NEE)
Time frame: 24 hours
RRT session fluid balance
Time frame: 24 hours
24-hour fluid balance
Time frame: 24 hours
Mortality in the intensive care unit
Time frame: 60 days
Mortality in the hospital
Time frame: 60 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2026.
- Individual participant dataSharing planned: Yes. Data will be shared upon reasonable request
Related trials for Acute Kidney Injury
Not yet recruiting
Vitamin C for Acute Kidney Injury in ACLF With Septic Shock: A Randomized Controlled Trial
Acute-on-Chronic Liver Failure (ACLF)
Not yet recruiting
Early Biomarker Kidney Injury Assessment After Acumen Directed Fluid Management in Cardiac Surgery
Renal Injury, Acute Kidney Injury
Recruiting
Acute Kidney Injury and Ultra-endurance Running
AKI (Acute Kidney Injury) Due to Trauma
Recruiting
WIN Ratio Analysis to Determine a Strategy of Non- Invasive SUpport for Respiratory Failure in the EmeRgency Department
Acute Hypoxic Respiratory Failure, Acute Respiratory Distress Syndrome (ARDS)
Not yet recruitingObservational study
Diastolic Shock Index for Predicting Hemodynamic Instability During Continuous Renal Replacement Therapy
Acute Kidney Injury, Hypotension (MeSH: D007022)
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. This study is not recruiting at the moment.
Carla Pontes, MD principal investigator
Federal University of São Paulo
Flavia R Machado, MD, PhD study chair
Federal University of São Paulo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Methylene Blue in people with Acute Kidney Injury and Shock, run by Federal University of São Paulo 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 4 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: finished, as of the sponsor's last update on 17 Apr 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite Endpoint (time frame: 6 hours). 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 17 Apr 2026.