Septic ShockPhase 2/3NCT06005558
Low Dose Versus High Dose Methylene Blue in Septic Patients
A Phase 2/3 study testing Normal saline, Methylene Blue low dose and Methylene Blue high dose in people with Septic Shock, run by National Cancer Institute, Egypt at 1 site in Egypt.
Trial summary
The main aim of this study is to examine the various effects of continuous methylene blue infusion in septic cancer patients and to compare it with the traditional infusion of noradrenaline in such patients . Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Septic Shock
- What is being tested?
- Normal saline, Methylene Blue low dose and Methylene Blue high dose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Aug 2023to 15 May 2024
- Phase
- Phase 2/3
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged ≥ 18 years and ≤ 65 with septic shock as defined by Sepsis-3 criteria (confirmed infection, requiring vasopressor to maintain a mean arterial blood pressure (MAP) ≥ 65 mmHg, and serum lactate > 2 mmol/L after adequate fluid resuscitation), and requiring mechanical ventilation.
Who cannot join
- myocardial infarction or cerebrovascular accident within the last 3 months.
- severe lung , liver or kidney disease (creatinine >3.5 mg/dL).
- pregnancy.
- glucose 6-phosphate-dehydrogenase deficiency.
- known allergy to MB or food dyes and the use of nitrates within the last 3 days.
- more than 24 hrs since initiation of norepinephrine.
Show all 9Show fewer
- other causes of shock than sepsis .
- recent intake (4-weeks) of selective serotonin re-uptake inhibitors or MAOi.
- refusal of the patient guardian to participate.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparative Study Between High and Low Dose Methylene Blue Infusion in Septic Cancer Patients. A Randomized Blinded Controlled Study
The main aim of this study is to examine the various effects of continuous methylene blue infusion in septic cancer patients and to compare it with the traditional infusion of noradrenaline in such patients .
Read the detailed description
Exaggerated host response to infection, may result in sepsis, which is life-threatening organ dysfunction . Though considered the number one cause of in-hospital deaths , it can be treatable with early prompt interventions.
The 2021 SSC Guidelines use the Third International Consensus definitions, also known as Sepsis-3. Where sepsis is defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection." Organ dysfunction is evidenced by an increased score of 2 or more in the Quick Sequential [Sepsis-related] Organ Failure Assessment (QSOFA), and septic shock is considered as "a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone." To diagnose septic shock, an euvolemic patient must require vasopressor support to achieve a mean arterial pressure of at least 65 mm Hg and have a lactate level above 2 mmol/L.
The triad of intravenous fluid, vasopressors and antibiotics in the first hour is the mainstay of septic shock management. Aim of management is to maintain patient hemodynamically stable until antibiotics kick in and fight infection. In case of non-responders, low dose corticosteroids are prescribed. Other drugs need to be studied to also help in cases of non-responders and to improve outcome in general. Methylene blue (MB) is a nitric oxide inhibitor that can counteract the vasodilatation in early septic shock.
Nitric oxide (NO) activates soluble guanylyl cyclase (sGC) which activates cyclic guanosine monophosphate (cGMP)-dependent protein kinases (PKGs) that cause vasodilatation. Methylene blue selectively blocks sGC and inhibits iNOS. Therefore, it selectively acts on the microcirculation.
Onset of action of intravenous MB is 30-60 min. Peak concentration at 30 min. It is excreted through bile and fecal routes plus through the kidneys. Due to the short Plasma half-life of 5-6 hours, some studies used continuous infusion of 0.25-2 mg/kg/h, for up to 3 days following the initial bolus dose
- Conditions
- Septic Shock
- Being tested
- Normal saline, Methylene Blue low dose, Methylene Blue high dose
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Normal salineDrug
Also called Control
100 ml 0.9% Nacl over 20 minutes, followed by continuous infusion of normal saline for 72 hours.
Methylene Blue low doseDrug
Also called Low dose
A bolus of MB 1mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.
Methylene Blue high doseDrug
Also called High dose
A bolus of MB 4mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.
| Study group | Role | What they receive |
|---|---|---|
| Normal saline | Active comparator | 30 patients will receive placebo of 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of Nacl for 72 hours. Receives: Drug: Methylene Blue low dose; Drug: Methylene Blue high dose |
| methylene blue low dose | Active comparator | 30 patients will receive a bolus of MB 1mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours. Receives: Drug: Normal saline; Drug: Methylene Blue high dose |
| methylene blue high dose | Active comparator | 30 patients will receive a bolus of MB 4mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours. Receives: Drug: Normal saline; Drug: Methylene Blue low dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Discontinuation of vasopressor
Time for noradrenaline discontinuation
Measured: 7 days
Secondary outcomes (1)
Mortality
Number of deaths
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2023
- Study start1 Aug 2023
- Primary completion29 Apr 2024
- Study completion15 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- 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
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute, Egypt
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ehab Hanafy Shaker, National Cancer Institute, Egypt
- Investigators
- Ehab H Shaker, MD, Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06005558
- Sponsor's protocol ID
- Methylene blue
- Status last verified
- Jul 2024
- First submitted
- 15 Aug 2023
- Last updated
- 5 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: After study completion and study publication we can share IPD upon request.
Publications
Chalise SN, Sahib TA, Boyer GA, Pathak V. Methylene Blue in Refractory Shock. Cureus. 2022 Nov 6;14(11):e31158. doi: 10.7759/cureus.31158. eCollection 2022 Nov.
PubMed 36505110Shaker EH, Soliman AM, Bedewy AAE, Elrawas MM. Comparative study between high and low dose methylene blue infusion in septic cancer patients: a randomized, blinded, controlled study. BMC Anesthesiol. 2025 Jan 8;25(1):15. doi: 10.1186/s12871-024-02792-3.
PubMed 39780053
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Study Between High and Low Dose Methylene Blue Infusion in Septic Cancer Patients. A Randomized Blinded Controlled Study
- ClinicalTrials.gov ID
- NCT06005558
- Acronym / sponsor ID
- Methylene blue
- Conditions
- Septic Shock
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- National Cancer Institute, EgyptUniversity, hospital or other
- Study start
- 1 Aug 2023 (actual)
- Primary completion
- 29 Apr 2024 (actual)
- Study completion
- 15 May 2024 (actual)
- First posted
- 22 Aug 2023 (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 main aim of this study is to examine the various effects of continuous methylene blue infusion in septic cancer patients and to compare it with the traditional infusion of noradrenaline in such patients .
Detailed description
Exaggerated host response to infection, may result in sepsis, which is life-threatening organ dysfunction . Though considered the number one cause of in-hospital deaths , it can be treatable with early prompt interventions.
The 2021 SSC Guidelines use the Third International Consensus definitions, also known as Sepsis-3. Where sepsis is defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection." Organ dysfunction is evidenced by an increased score of 2 or more in the Quick Sequential [Sepsis-related] Organ Failure Assessment (QSOFA), and septic shock is considered as "a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone." To diagnose septic shock, an euvolemic patient must require vasopressor support to achieve a mean arterial pressure of at least 65 mm Hg and have a lactate level above 2 mmol/L.
The triad of intravenous fluid, vasopressors and antibiotics in the first hour is the mainstay of septic shock management. Aim of management is to maintain patient hemodynamically stable until antibiotics kick in and fight infection. In case of non-responders, low dose corticosteroids are prescribed. Other drugs need to be studied to also help in cases of non-responders and to improve outcome in general. Methylene blue (MB) is a nitric oxide inhibitor that can counteract the vasodilatation in early septic shock.
Nitric oxide (NO) activates soluble guanylyl cyclase (sGC) which activates cyclic guanosine monophosphate (cGMP)-dependent protein kinases (PKGs) that cause vasodilatation. Methylene blue selectively blocks sGC and inhibits iNOS. Therefore, it selectively acts on the microcirculation.
Onset of action of intravenous MB is 30-60 min. Peak concentration at 30 min. It is excreted through bile and fecal routes plus through the kidneys. Due to the short Plasma half-life of 5-6 hours, some studies used continuous infusion of 0.25-2 mg/kg/h, for up to 3 days following the initial bolus dose
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Normal saline | Active comparator | Drug: Methylene Blue low dose, Drug: Methylene Blue high dose30 patients will receive placebo of 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of Nacl for 72 hours. |
| methylene blue low dose | Active comparator | Drug: Normal saline, Drug: Methylene Blue high dose30 patients will receive a bolus of MB 1mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours. |
| methylene blue high dose | Active comparator | Drug: Normal saline, Drug: Methylene Blue low dose30 patients will receive a bolus of MB 4mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients aged ≥ 18 years and ≤ 65 with septic shock as defined by Sepsis-3 criteria (confirmed infection, requiring vasopressor to maintain a mean arterial blood pressure (MAP) ≥ 65 mmHg, and serum lactate > 2 mmol/L after adequate fluid resuscitation), and requiring mechanical ventilation.
Key exclusion criteria (9 listed)
- myocardial infarction or cerebrovascular accident within the last 3 months.
- severe lung , liver or kidney disease (creatinine >3.5 mg/dL).
- pregnancy.
- glucose 6-phosphate-dehydrogenase deficiency.
- known allergy to MB or food dyes and the use of nitrates within the last 3 days.
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 |
|---|---|---|
| Normal salineAlso: Control100 ml 0.9% Nacl over 20 minutes, followed by continuous infusion of normal saline for 72 hours. | Drug | methylene blue high dose, methylene blue low dose |
| Methylene Blue low doseAlso: Low doseA bolus of MB 1mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours. | Drug | Normal saline, methylene blue high dose |
| Methylene Blue high doseAlso: High doseA bolus of MB 4mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours. | Drug | Normal saline, methylene blue low dose |
Primary outcome
Discontinuation of vasopressor
Time frame: 7 days
Time for noradrenaline discontinuation
1 secondary outcome
Mortality
Time frame: 28 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 5 Jul 2024.
- Results publication: PubMed 36505110Chalise SN, Sahib TA, Boyer GA, Pathak V. Methylene Blue in Refractory Shock. Cureus. 2022 Nov 6;14(11):e31158. doi: 10.7759/cureus.31158. eCollection 2022 Nov.
- Derived from this study: PubMed 39780053Shaker EH, Soliman AM, Bedewy AAE, Elrawas MM. Comparative study between high and low dose methylene blue infusion in septic cancer patients: a randomized, blinded, controlled study. BMC Anesthesiol. 2025 Jan 8;25(1):15. doi: 10.1186/s12871-024-02792-3.
- Individual participant dataSharing planned: No. After study completion and study publication we can share IPD upon request.
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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. This study is not recruiting at the moment.
Ehab H Shaker, MD principal investigator
National Cancer Institute (NCI)
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 Normal saline, Methylene Blue low dose and Methylene Blue high dose in people with Septic Shock, run by National Cancer Institute, Egypt at 1 site in Egypt.
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: finished, as of the sponsor's last update on 5 Jul 2024. 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 Egypt. 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?
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?
Discontinuation of vasopressor (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06005558, which also lists 2 linked publications.
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 5 Jul 2024.