Septic ShockPhase 2/3SHOCKEM-BlueNCT04446871
Methylene Blue in Early Septic Shock
A Phase 2/3 study testing 0.9% sodium chloride and Methylene Blue in people with Septic Shock, run by Hospital Civil de Guadalajara at 1 site in Mexico.
Trial summary
Septic shock is a subset of sepsis characterized by a decrease in vascular tone, which contributes to impaired regional blood flow distribution, and leads to organic failure. Besides intravenous fluids and adequate antimicrobial therapy, patients with septic shock require vasopressor support, which can lead to many… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Septic Shock
- What is being tested?
- 0.9% sodium chloride and Methylene Blue
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 91 participants
- Where
- 1 siteMexico
- Study dates
- 17 Mar 2017to 25 Jan 2021
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Septic shock diagnosis, according to the Sepsis-3 consensus.
- Prior adequate fluid resuscitation according to dynamic predictors of volume responsiveness.
- More than 6 h and less than 24 h of norepinephrine requirement to maintain a mean arterial pressure ≥65 mmHg.
Who cannot join
- Age < 18 years.
- Pregnancy.
- Not expected to survive 48 hours.
- Presence or high suspicion of concurrent hemorrhagic, obstructive or hypovolemic shock.
- Personal or familiar history of glucose-6-phosphate dehydrogenase deficiency.
- Allergic to methylene blue, phenothiazines, or food dyes.
- Recent intake (4-weeks) of selective serotonin re-uptake inhibitors.
- Refusal of the patient or decision maker to enroll in the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Early Use of Methylene Blue in Patients With Septic Shock: a Pilot Randomized Controlled Trial
Septic shock is a subset of sepsis characterized by a decrease in vascular tone, which contributes to impaired regional blood flow distribution, and leads to organic failure. Besides intravenous fluids and adequate antimicrobial therapy, patients with septic shock require vasopressor support, which can lead to many adverse effects, therefore, non-vasopressor agents that can improve hemodynamic status are needed. In this randomized controlled-study, the investigators will address the efficacy and safety of infusion with methylene blue in patients with septic shock.
Read the detailed description
Unlike sepsis, septic shock mortality is not declining for the last decade, and is still around 40%. After restoring intravascular volume, many patients need vasopressor agents to maintain arterial blood pressure, which leads to improvement of perfusion at some vascular beds, however some organs may suffer from maldistribution of blood flow. These changes of regional blood flow may compromise oxygen delivery and perpetuate the inflammation and tissue damage associated with the state of shock.
One of the main mechanisms of vasodilation after inflammatory insults, is the activation of the inducible isoform of Nitric Oxide Synthase (iNOS), and the subsequent increase in the levels of nitric oxide, which even reduces the response to vasoconstrictor agents. Methylene blue (MB) is a selective inhibitor of iNOS, which has been used successfully in patients with post-cardiopulmonary bypass associated vasoplegia, however, the evidence of the use of MB in septic shock patients is limited to case reports, observational and small studies. In this randomized controlled trial, the investigators will compare the efficacy and safety outcomes of repeated doses of MB in patients with septic shock.
- Conditions
- Septic Shock
- Being tested
- 0.9% sodium chloride, Methylene Blue
- Keywords
- Septic shock, Methylene blue, Norepinephrine
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
0.9% sodium chlorideDrug
Intravenous infusion of 500 cc of 0.9% sodium chloride solution for 6 h, once a day for a total of 3 doses.
Methylene BlueDrug
Intravenous infusion of 100 mg methylene blue in 500 cc of 0.9% sodium chloride solution for 6 h, once a day for a total of 3 doses.
| Study group | Role | What they receive |
|---|---|---|
| Standard care | Placebo comparator | Placebo Receives: Drug: 0.9% sodium chloride |
| Methylene blue | Experimental | Methylene blue Receives: Drug: Methylene Blue |
What is being measured
The primary outcome is the main question the study is designed to answer.
Vasopressor requirement
Total time to shock resolution (hours)
Measured: 28 days
Secondary outcomes (3)
Time to lactate normalization
Time in hours until lactate is <2 mmol/L
Measured: 7 days
Length of stay in intensive care unit
Time in days until ICU discharge
Measured: 28 days
Intensive care unit mortality
Mortality in intensive care unit
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 posted25 Jun 2020
- Study start17 Mar 2017
- Primary completion10 Dec 2020
- Study completion25 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 91 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Civil de Guadalajara
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Miguel Á Ibarra-Estrada, Hospital Civil de Guadalajara
- Investigators
- Miguel Ibarra-Estrada, MD, Principal investigator, Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04446871
- Sponsor's protocol ID
- HCG/CEI-0252/17
- Acronym
- SHOCKEM-Blue
- Status last verified
- Nov 2022
- First submitted
- 22 Jun 2020
- Last updated
- 4 Nov 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ibarra-Estrada M, Kattan E, Aguilera-Gonzalez P, Sandoval-Plascencia L, Rico-Jauregui U, Gomez-Partida CA, Ortiz-Macias IX, Lopez-Pulgarin JA, Chavez-Pena Q, Mijangos-Mendez JC, Aguirre-Avalos G, Hernandez G. Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial. Crit Care. 2023 Mar 13;27(1):110. doi: 10.1186/s13054-023-04397-7.
PubMed 36915146
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Use of Methylene Blue in Patients With Septic Shock: a Pilot Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04446871
- Acronym / sponsor ID
- SHOCKEM-Blue / HCG/CEI-0252/17
- Conditions
- Septic Shock
- Keywords
- Septic shock, Methylene blue, Norepinephrine
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 91 participants (actual)
- Lead sponsor
- Hospital Civil de GuadalajaraUniversity, hospital or other
- Study start
- 17 Mar 2017 (actual)
- Primary completion
- 10 Dec 2020 (actual)
- Study completion
- 25 Jan 2021 (actual)
- First posted
- 25 Jun 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.
Septic shock is a subset of sepsis characterized by a decrease in vascular tone, which contributes to impaired regional blood flow distribution, and leads to organic failure. Besides intravenous fluids and adequate antimicrobial therapy, patients with septic shock require vasopressor support, which can lead to many adverse effects, therefore, non-vasopressor agents that can improve hemodynamic status are needed. In this randomized controlled-study, the investigators will address the efficacy and safety of infusion with methylene blue in patients with septic shock.
Detailed description
Unlike sepsis, septic shock mortality is not declining for the last decade, and is still around 40%. After restoring intravascular volume, many patients need vasopressor agents to maintain arterial blood pressure, which leads to improvement of perfusion at some vascular beds, however some organs may suffer from maldistribution of blood flow. These changes of regional blood flow may compromise oxygen delivery and perpetuate the inflammation and tissue damage associated with the state of shock.
One of the main mechanisms of vasodilation after inflammatory insults, is the activation of the inducible isoform of Nitric Oxide Synthase (iNOS), and the subsequent increase in the levels of nitric oxide, which even reduces the response to vasoconstrictor agents. Methylene blue (MB) is a selective inhibitor of iNOS, which has been used successfully in patients with post-cardiopulmonary bypass associated vasoplegia, however, the evidence of the use of MB in septic shock patients is limited to case reports, observational and small studies. In this randomized controlled trial, the investigators will compare the efficacy and safety outcomes of repeated doses of MB in patients with septic shock.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard care | Placebo comparator | Drug: 0.9% sodium chloridePlacebo |
| Methylene blue | Experimental | Drug: Methylene BlueMethylene blue |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Septic shock diagnosis, according to the Sepsis-3 consensus.
- Prior adequate fluid resuscitation according to dynamic predictors of volume responsiveness.
- More than 6 h and less than 24 h of norepinephrine requirement to maintain a mean arterial pressure ≥65 mmHg.
Key exclusion criteria (8 listed)
- Age < 18 years.
- Pregnancy.
- Not expected to survive 48 hours.
- Presence or high suspicion of concurrent hemorrhagic, obstructive or hypovolemic shock.
- Personal or familiar history of glucose-6-phosphate dehydrogenase 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 |
|---|---|---|
| 0.9% sodium chlorideIntravenous infusion of 500 cc of 0.9% sodium chloride solution for 6 h, once a day for a total of 3 doses. | Drug | Standard care |
| Methylene BlueIntravenous infusion of 100 mg methylene blue in 500 cc of 0.9% sodium chloride solution for 6 h, once a day for a total of 3 doses. | Drug | Methylene blue |
Primary outcome
Vasopressor requirement
Time frame: 28 days
Total time to shock resolution (hours)
3 secondary outcomes
Time to lactate normalization
Time frame: 7 days
Length of stay in intensive care unit
Time frame: 28 days
Intensive care unit 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 4 Nov 2022.
- Derived from this study: PubMed 36915146Ibarra-Estrada M, Kattan E, Aguilera-Gonzalez P, Sandoval-Plascencia L, Rico-Jauregui U, Gomez-Partida CA, Ortiz-Macias IX, Lopez-Pulgarin JA, Chavez-Pena Q, Mijangos-Mendez JC, Aguirre-Avalos G, Hernandez G. Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial. Crit Care. 2023 Mar 13;27(1):110. doi: 10.1186/s13054-023-04397-7.
- Individual participant dataSharing planned: No
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Serum GDF-15 and LGALS3BP as Prognostic Biomarkers in Sepsis
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Hemodynamic Resuscitation Guided by Non-Invasive Mean Systemic Filling Pressure to Prevent Acute Kidney Injury in Septic Shock
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Veno-arterial Carbon Dioxide Partial Pressure Difference (CO2gap) for Early Resuscitation of Septic Shock
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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.
Miguel Ibarra-Estrada, MD principal investigator
Investigator
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 0.9% sodium chloride and Methylene Blue in people with Septic Shock, run by Hospital Civil de Guadalajara at 1 site in Mexico.
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 3 inclusion and 8 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 4 Nov 2022. 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 Mexico. 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. Some participants in this study may receive a placebo. 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?
Vasopressor requirement (time frame: 28 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 NCT04446871, which also lists 1 linked publication.
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 4 Nov 2022.