Methylene Blue for the Prevention of Hypotension During Hemodialysis (BLUE)

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.

Study Overview

• Status: Completed
• Conditions: Shock; Acute Kidney Injury; Intradialytic Hypotension; Intradialytic Hypertension in Hemodialysis Patients
• Intervention / Treatment: Other: Control; Drug: Methylene Blue

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 Type: Interventional
• Enrollment (Actual): 261
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • São Paulo, São Paulo, Brazil, 04038002
      • Federal University of São Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• Prior participation in the study
• Acute coronary syndrome
• Chronic nitrate oral use

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Methylene Blue; Methylene blue will be infused during renal replacement therapy	Drug: Methylene Blue; 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
Other: Control; usual care	Other: Control; Usual care during renal replacement therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	6 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypotension	Mean blood pressure below 65 mmHg for at least 5 minutes during renal replacement therapy	6 hours
Maximum vasopressor dose	Maximum vasopressor dose, in micro-grams per kilogram per minute used during de first 24 hours	24 hours
Mortality in the intensive care unit	Death in the intensive care unit	60 days
Mortality in the hospital	Death during hospital stay	60 days
Norepinephrine equivalent dose (NEE)	The cumulative norepinephrine equivalent dose (NEE)	24 hours
RRT session fluid balance	The fluid balance of RTT session	24 hours
24-hour fluid balance	The fluid balance on 24-hour after RTT session	24 hours

Collaborators and Investigators

• Sponsor: Federal University of São Paulo
• Investigators: Principal Investigator: Carla Pontes, MD, Federal University of São Paulo; Study Chair: Flavia R Machado, MD, PhD, Federal University of São Paulo

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2021
• Primary Completion (Actual): December 16, 2025
• Study Completion (Actual): December 16, 2025

Study Registration Dates

• First Submitted: October 13, 2021
• First Submitted That Met QC Criteria: October 13, 2021
• First Posted (Actual): October 25, 2021

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 12, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: hemodialysis; methylene blue; intradialytic hypotension
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Acute Kidney Injury; Shock; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Phenothiazines; Methylene Blue
• Other Study ID Numbers: BLUE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared upon reasonable request
• IPD Sharing Time Frame: 6 months after trial is published
• IPD Sharing Access Criteria: After aproval by the executive comittee
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No