Septic ShockPhase 4CRuMBSNCT03120637
Evaluating in Cirrhotics With Refractory Vasoplegia the Effect of Methylene Blue
A Phase 4 study testing Methylene Blue in people with Septic Shock and Vasoplegia, run by Institute of Liver and Biliary Sciences, India at 1 site in India.
Trial summary
Mortality rates associated septic shock remains unacceptably high, around 20-50%, with refractory hypotension in half of these patients. Widespread vasodilatation involves the activation of the soluble intracellular enzyme guanylate cyclase (GC) by nitric oxide (NO), resulting in the production of cyclic guanosine… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock, Vasoplegia, Cirrhosis, Liver
- 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
- 111 participants
- Where
- 1 siteIndia
- Study dates
- 1 Jan 2017to 10 Jan 2018
- Phase
- Phase 4
- 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
- Adult patients (>18 years )
- Refractory septic shock (Noradrenaline >0.5mcg/kg/mt )
Who cannot join
- Declined consent
- Pregnancy
- Less than 18 years old
- Immunosuppressant patients (e.g. on steroid medication, active anti-cancer chemotherapeutic agent, etc.)
- Glucose-6-phosphate dehydrogenase deficiency
- Medication of Serotonin modulator/SSRI
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- Pre-existing Pulmonary Hypertension
- CKD-Stage IV/V
- Patients with GI bleed
- Patients on DNR
- Patients declared Brain dead
Trial locations and contacts
1 site in 1 country.
India1 site
Liver Coma ICU, Institute of Liver and Biliary Sciences
New Delhi, National Capital Territory of Delhi, 110070
About this study
Official title: Evaluating in Cirrhotics With Refractory Vasoplegia the Effect of Methylene Blue in Sepsis: A Randomized Controlled Trial
Mortality rates associated septic shock remains unacceptably high, around 20-50%, with refractory hypotension in half of these patients. Widespread vasodilatation involves the activation of the soluble intracellular enzyme guanylate cyclase (GC) by nitric oxide (NO), resulting in the production of cyclic guanosine monophosphate (cGMP). Initially discovered as an endothelium-derived relaxing factor in blood vessels, NO is made by the enzyme nitric oxide synthase (NOS). It has been suggested that the inhibition of NO generation might be a treatment option for sepsis and septic shock. Methylene blue (MB) is a dye that easily crosses cell membranes, inhibits iNOS, and is capable of inhibiting the GC enzyme in vascular smooth muscle cells.Early use of MB can block the progressive decrease in systemic vascular resistance of patients unresponsive to noradrenaline and mitigate the need for prolonged vasoconstrictor use. The investigators propose to study the effect of methylene blue on cirrhotic adults with sepsis, with refractory vasoplegia unresponsive to maximum doses of noradrenaline and vasopressin.
- Conditions
- Septic Shock, Vasoplegia, Cirrhosis, Liver, Refractory Shock
- Being tested
- Methylene Blue
- Keywords
- Methylene Blue, Septic Shock, Vasoplegia, Cirrhosis
- Medical subject headings
- Shock, Septic, Vasoplegia, Liver Cirrhosis, Shock, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylene BlueDrug
| Study group | Role | What they receive |
|---|---|---|
| Methylene Blue | Experimental | Methylene Blue intravenous route, 2 mg/kg Loading Dose over 30 minutes, followed by 0.5 mg/kg/hr for 6 hours Receives: Drug: Methylene Blue |
| Standard Treatment | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival in both groups
Measured: 2 days
Secondary outcomes (3)
Systemic Vascular Resistance
Change in SVR
Measured: 6 hours
Mean Arterial Pressure
Improvement in MAP
Measured: 6 hours
Decrease of vasopressor dose of 20 percent from time of start of test drug.
Effect on decreasing vasopressor doses
Measured: 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2017
- Study start1 Jan 2017
- Primary completion10 Jan 2018
- Study completion10 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- More trials run by Institute of Liver and Biliary Sciences, IndiaThe 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 4
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 111 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Liver and Biliary Sciences, India
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Karthik Ponnappan, MD, Principal investigator, Institute of Liver and Biliary Sciences, India
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03120637
- Sponsor's protocol ID
- ILBS-Septic Shock-01
- Acronym
- CRuMBS
- Status last verified
- Jan 2018
- First submitted
- 28 Feb 2017
- Last updated
- 30 Jan 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bassi E, Park M, Azevedo LC. Therapeutic strategies for high-dose vasopressor-dependent shock. Crit Care Res Pract. 2013;2013:654708. doi: 10.1155/2013/654708. Epub 2013 Sep 15.
PubMed 24151551Park BK, Shim TS, Lim CM, Lee SD, Kim WS, Kim DS, Kim WD, Koh Y. The effects of methylene blue on hemodynamic parameters and cytokine levels in refractory septic shock. Korean J Intern Med. 2005 Jun;20(2):123-8. doi: 10.3904/kjim.2005.20.2.123.
PubMed 16134766Kirov MY, Evgenov OV, Evgenov NV, Egorina EM, Sovershaev MA, Sveinbjornsson B, Nedashkovsky EV, Bjertnaes LJ. Infusion of methylene blue in human septic shock: a pilot, randomized, controlled study. Crit Care Med. 2001 Oct;29(10):1860-7. doi: 10.1097/00003246-200110000-00002.
PubMed 11588440Memis D, Karamanlioglu B, Yuksel M, Gemlik I, Pamukcu Z. The influence of methylene blue infusion on cytokine levels during severe sepsis. Anaesth Intensive Care. 2002 Dec;30(6):755-62. doi: 10.1177/0310057X0203000606.
PubMed 12500513Juffermans NP, Vervloet MG, Daemen-Gubbels CR, Binnekade JM, de Jong M, Groeneveld AB. A dose-finding study of methylene blue to inhibit nitric oxide actions in the hemodynamics of human septic shock. Nitric Oxide. 2010 May 15;22(4):275-80. doi: 10.1016/j.niox.2010.01.006. Epub 2010 Jan 28.
PubMed 20109575
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating in Cirrhotics With Refractory Vasoplegia the Effect of Methylene Blue in Sepsis: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03120637
- Acronym / sponsor ID
- CRuMBS / ILBS-Septic Shock-01
- Conditions
- Septic Shock, Vasoplegia, Cirrhosis, Liver, Refractory Shock
- Keywords
- Methylene Blue, Septic Shock, Vasoplegia, Cirrhosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 111 participants (actual)
- Lead sponsor
- Institute of Liver and Biliary Sciences, IndiaUniversity, hospital or other
- Study start
- 1 Jan 2017 (actual)
- Primary completion
- 10 Jan 2018 (actual)
- Study completion
- 10 Jan 2018 (actual)
- First posted
- 19 Apr 2017 (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.
Mortality rates associated septic shock remains unacceptably high, around 20-50%, with refractory hypotension in half of these patients. Widespread vasodilatation involves the activation of the soluble intracellular enzyme guanylate cyclase (GC) by nitric oxide (NO), resulting in the production of cyclic guanosine monophosphate (cGMP). Initially discovered as an endothelium-derived relaxing factor in blood vessels, NO is made by the enzyme nitric oxide synthase (NOS). It has been suggested that the inhibition of NO generation might be a treatment option for sepsis and septic shock. Methylene blue (MB) is a dye that easily crosses cell membranes, inhibits iNOS, and is capable of inhibiting the GC enzyme in vascular smooth muscle cells.Early use of MB can block the progressive decrease in systemic vascular resistance of patients unresponsive to noradrenaline and mitigate the need for prolonged vasoconstrictor use. The investigators propose to study the effect of methylene blue on cirrhotic adults with sepsis, with refractory vasoplegia unresponsive to maximum doses of noradrenaline and vasopressin.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methylene Blue | Experimental | Drug: Methylene BlueMethylene Blue intravenous route, 2 mg/kg Loading Dose over 30 minutes, followed by 0.5 mg/kg/hr for 6 hours |
| Standard Treatment | No intervention | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Adult patients (>18 years )
- Refractory septic shock (Noradrenaline >0.5mcg/kg/mt )
Key exclusion criteria (11 listed)
- Declined consent
- Pregnancy
- Less than 18 years old
- Immunosuppressant patients (e.g. on steroid medication, active anti-cancer chemotherapeutic agent, etc.)
- 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 |
|---|---|---|
| Methylene Blue | Drug | Methylene Blue |
Primary outcome
Survival in both groups
Time frame: 2 days
3 secondary outcomes
Systemic Vascular Resistance
Time frame: 6 hours
Mean Arterial Pressure
Time frame: 6 hours
Decrease of vasopressor dose of 20 percent from time of start of test drug.
Time frame: 6 hours
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 30 Jan 2018.
- Results publication: PubMed 24151551Bassi E, Park M, Azevedo LC. Therapeutic strategies for high-dose vasopressor-dependent shock. Crit Care Res Pract. 2013;2013:654708. doi: 10.1155/2013/654708. Epub 2013 Sep 15.
- Results publication: PubMed 16134766Park BK, Shim TS, Lim CM, Lee SD, Kim WS, Kim DS, Kim WD, Koh Y. The effects of methylene blue on hemodynamic parameters and cytokine levels in refractory septic shock. Korean J Intern Med. 2005 Jun;20(2):123-8. doi: 10.3904/kjim.2005.20.2.123.
- Results publication: PubMed 11588440Kirov MY, Evgenov OV, Evgenov NV, Egorina EM, Sovershaev MA, Sveinbjornsson B, Nedashkovsky EV, Bjertnaes LJ. Infusion of methylene blue in human septic shock: a pilot, randomized, controlled study. Crit Care Med. 2001 Oct;29(10):1860-7. doi: 10.1097/00003246-200110000-00002.
- Results publication: PubMed 12500513Memis D, Karamanlioglu B, Yuksel M, Gemlik I, Pamukcu Z. The influence of methylene blue infusion on cytokine levels during severe sepsis. Anaesth Intensive Care. 2002 Dec;30(6):755-62. doi: 10.1177/0310057X0203000606.
- Results publication: PubMed 20109575Juffermans NP, Vervloet MG, Daemen-Gubbels CR, Binnekade JM, de Jong M, Groeneveld AB. A dose-finding study of methylene blue to inhibit nitric oxide actions in the hemodynamics of human septic shock. Nitric Oxide. 2010 May 15;22(4):275-80. doi: 10.1016/j.niox.2010.01.006. Epub 2010 Jan 28.
- Individual participant dataSharing planned: No
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Septic Shock
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.
Karthik Ponnappan, MD principal investigator
Institute of Liver and Biliary Sciences, India
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Methylene Blue in people with Septic Shock and Vasoplegia, run by Institute of Liver and Biliary Sciences, India at 1 site in India.
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 11 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 30 Jan 2018. 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 India. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Survival in both groups (time frame: 2 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 NCT03120637, which also lists 5 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 30 Jan 2018.