Septic ShockPhase 3NCT04295993
Methylene Blue and Microcirculation in Septic Shock
A Phase 3 study testing Methylene Blue and Norepinephrine infusion in people with Septic Shock, run by Cairo University at 1 site in Egypt.
Trial summary
This trial aims to identify the effects of methylene blue infusion on the the micro-circulation in patients with septic shock. The investigators will evaluate various indices of micro-circulation such as: microvascular flow index, the flow heterogeneity index, the total vessel density, the perfused vessel density, and… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Septic Shock
- What is being tested?
- Methylene Blue and Norepinephrine infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteEgypt
- Study dates
- 10 Mar 2020to 20 Sep 2020
- Phase
- Phase 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Septic shock
- The patient is on norepinephrine infusion
Who cannot join
- Elevated serum creatinine (above 1.4 mg/dL)
- Pregnancy
Trial locations and contacts
1 site in 1 country.
Egypt1 site
Cairo University
Cairo
Ashraf Rady, Professor, ashrafrady83@gmail.com
About this study
Official title: The Effect of Methylene Blue on Microcirculation in Patients With Septic Shock: a Randomized Controlled Trial
This trial aims to identify the effects of methylene blue infusion on the the micro-circulation in patients with septic shock. The investigators will evaluate various indices of micro-circulation such as: microvascular flow index, the flow heterogeneity index, the total vessel density, the perfused vessel density, and the proportion of perfused vessels.
Read the detailed description
The mortality rate of patients with septic shock remains very high. Arterial hypotension, related to arteriolar vasodilation and myocardial depression are the mainstays of septic shock pathology.
At the level of the micro-circulation, there is insufficient delivery of oxygen to organs and tissues which results in organ dysfunction and potential organ necrosis.One key factor leading to vascular dysfunction is the inappropriately increased production of nitric oxide within the blood vessel endothelium. Elevated levels of nitric oxide results in the blood vessel endothelium receiving direct vasodilator input, as well as the inability to respond to norepinephrine-mediated vasoconstriction. Nitric oxide activates the soluble isoform of the enzyme guanylatecyclase, which in turn increases production of cyclic guanosine monophosphate. Nitric oxide has other beneficial effects which are mediated via other pathways than guanylatecyclase; therefore, administration of a guanylate cyclase inhibitor such as methylene blue could be a safer therapeutic option than the inhibition of nitric oxide production.
These effects of methylene blue could be related to vasoconstriction and positive inotropic effects as well to an increase in blood volume, itself related to a decrease in vascular permeability. The use of methylene blue has been recently advocated as a potential adjunct in the treatment of shock states. However, the effect of MB at the level of the capillary bed, where vital exchange of oxygen and nutrients occurs, is unknown. Thus in this study, the investigators will investigate the effect of methylene blue in combination with NE at the microvascular level in septic shock.
- Conditions
- Septic Shock
- Being tested
- Methylene Blue, Norepinephrine infusion
- 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 BlueDrug
The patient will receive Methylene Blue bolus with a dose of 2 mg/kg over 10 minutes.
Norepinephrine infusionDrug
Also called Levophed
The patient will receive norepinephrine infusion to maintain mean arterial pressure above 65 mmHg
| Study group | Role | What they receive |
|---|---|---|
| methylene blue group | Experimental | The patients in this group will receive methylene blue bolus in addition to the norepinephrine infusion. Receives: Drug: Methylene Blue; Drug: Norepinephrine infusion |
| Norepinephrine group | Active comparator | The patients in this group will receive norepinephrine infusion. Receives: Drug: Norepinephrine infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Microvascular flow index
The image will be divided into four quadrants and the vessels <20 μ m diameter will be assigned a score based on the predominant flow characteristics of the vessels in that quadrant (0 = absent flow; 1 = intermittent; 2 = sluggish; 3 = normal). The values in each quadrant will be averaged to give an microvascular flow index for each sublingual site at each time point. To determine heterogeneity of perfusion, the flow heterogeneity index will be calculated as the highest microvascular flow index minus the lowest microvascular flow index divided by the mean microvascular flow index.
Measured: 6 hours
Secondary outcomes (9)
Total vessel density
The number of vessels per millimeters squared.
Measured: 6 hours
Perfused vessel density
The number of vessels multiplied by the fraction of perfused vessels
Measured: 6 hours
Proportion of perfused vessel
The number of vessels with flows 2 and 3 divided by the total number of vessels and multiplied by 100.
Measured: 6 hours
mean arterial pressure
the mean arterial blood pressure measured in mmHg
Measured: 24 hours
serum lactate
the value of lactate in the serum measured in milligrams per liter
Measured: 6 hours
length of stay in the intensive care unit
the duration of stay in the intensive care unit measured in days
Measured: 28 days
cardiac output
The amount of blood ejected by the heart in one minute measured in liters
Measured: 24 hours
total consumption of norepinephrine
the total consumption of norepinephrine in 6 hours measured in micrograms.
Measured: 6 hours
incidence of mortality
The number of dead patients divided by the total number of patients
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 posted5 Mar 2020
- Study start10 Mar 2020 (estimated)
- Primary completion10 Sep 2020 (estimated)
- Study completion20 Sep 2020 (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.
- More trials run by Cairo UniversityThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cairo University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kareman Mohammad Saad Eldin Abd El Ghafar, Cairo University
- Investigators
- Ahmed Mukhtar, Professor, Principal investigator, Professor of anesthesia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04295993
- Sponsor's protocol ID
- N-13-2019
- Status last verified
- Mar 2020
- First submitted
- 3 Mar 2020
- Last updated
- 5 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- 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 5 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Methylene Blue on Microcirculation in Patients With Septic Shock: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04295993
- Acronym / sponsor ID
- N-13-2019
- Conditions
- Septic Shock
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Cairo UniversityUniversity, hospital or other
- Study start
- 10 Mar 2020 (estimated)
- Primary completion
- 10 Sep 2020 (estimated)
- Study completion
- 20 Sep 2020 (estimated)
- First posted
- 5 Mar 2020 (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.
This trial aims to identify the effects of methylene blue infusion on the the micro-circulation in patients with septic shock. The investigators will evaluate various indices of micro-circulation such as: microvascular flow index, the flow heterogeneity index, the total vessel density, the perfused vessel density, and the proportion of perfused vessels.
Detailed description
The mortality rate of patients with septic shock remains very high. Arterial hypotension, related to arteriolar vasodilation and myocardial depression are the mainstays of septic shock pathology.
At the level of the micro-circulation, there is insufficient delivery of oxygen to organs and tissues which results in organ dysfunction and potential organ necrosis.One key factor leading to vascular dysfunction is the inappropriately increased production of nitric oxide within the blood vessel endothelium. Elevated levels of nitric oxide results in the blood vessel endothelium receiving direct vasodilator input, as well as the inability to respond to norepinephrine-mediated vasoconstriction. Nitric oxide activates the soluble isoform of the enzyme guanylatecyclase, which in turn increases production of cyclic guanosine monophosphate. Nitric oxide has other beneficial effects which are mediated via other pathways than guanylatecyclase; therefore, administration of a guanylate cyclase inhibitor such as methylene blue could be a safer therapeutic option than the inhibition of nitric oxide production.
These effects of methylene blue could be related to vasoconstriction and positive inotropic effects as well to an increase in blood volume, itself related to a decrease in vascular permeability. The use of methylene blue has been recently advocated as a potential adjunct in the treatment of shock states. However, the effect of MB at the level of the capillary bed, where vital exchange of oxygen and nutrients occurs, is unknown. Thus in this study, the investigators will investigate the effect of methylene blue in combination with NE at the microvascular level in septic shock.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| methylene blue group | Experimental | Drug: Methylene Blue, Drug: Norepinephrine infusionThe patients in this group will receive methylene blue bolus in addition to the norepinephrine infusion. |
| Norepinephrine group | Active comparator | Drug: Norepinephrine infusionThe patients in this group will receive norepinephrine infusion. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Septic shock
- The patient is on norepinephrine infusion
Key exclusion criteria (2 listed)
- Elevated serum creatinine (above 1.4 mg/dL)
- Pregnancy
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 BlueThe patient will receive Methylene Blue bolus with a dose of 2 mg/kg over 10 minutes. | Drug | methylene blue group |
| Norepinephrine infusionAlso: LevophedThe patient will receive norepinephrine infusion to maintain mean arterial pressure above 65 mmHg | Drug | Norepinephrine group, methylene blue group |
Primary outcome
Microvascular flow index
Time frame: 6 hours
The image will be divided into four quadrants and the vessels <20 μ m diameter will be assigned a score based on the predominant flow characteristics of the vessels in that quadrant (0 = absent flow; 1 = intermittent; 2 = sluggish; 3 = normal). The values in each quadrant will be averaged to give an microvascular flow index for each sublingual site at each time point. To determine heterogeneity of perfusion, the flow heterogeneity index will be calculated as the highest microvascular flow index minus the lowest microvascular flow index divided by the mean microvascular flow index.
9 secondary outcomes
Total vessel density
Time frame: 6 hours
Perfused vessel density
Time frame: 6 hours
Proportion of perfused vessel
Time frame: 6 hours
mean arterial pressure
Time frame: 24 hours
serum lactate
Time frame: 6 hours
length of stay in the intensive care unit
Time frame: 28 days
cardiac output
Time frame: 24 hours
total consumption of norepinephrine
Time frame: 6 hours
incidence of mortality
Time frame: 28 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2020.
- Individual participant dataSharing planned: No
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Sepsis
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A Trial of Adjunctive Fludrocortisone (50mcg, 100mcg or Placebo) in Critically Ill Patients With Septic Shock Receiving Hydrocortisone, Evaluating Survival and Functional Recovery and the Influence of Transcriptomic Response
Septic Shock
RecruitingObservational study
Clinical Value of EMR3 in Sepsis Diagnosis, Monitoring, and Prognosis: A Multicenter Prospective Observational Study
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Not yet recruiting
Hemodynamic Resuscitation Guided by Non-Invasive Mean Systemic Filling Pressure to Prevent Acute Kidney Injury in Septic Shock
Acute Kidney Injury Due to 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.
Ahmed Mukhtar, Professor principal investigator
Professor of anesthesia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Methylene Blue and Norepinephrine infusion in people with Septic Shock, run by Cairo University 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 2 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 5 Mar 2020. 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 phase mean?
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact kareman abdelghaffar, Demonstrator (+201223931469, kareman_86@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Microvascular flow index (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 5 Mar 2020.