Evaluating in Cirrhotics With Refractory Vasoplegia the Effect of Methylene Blue

Septic Shock Clinical Trial

— CRuMBS  

Official title:

Evaluating in Cirrhotics With Refractory Vasoplegia the Effect of Methylene Blue in Sepsis: A Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03120637
• Other study ID #: ILBS-Septic Shock-01
• Status: Completed
• Phase: Phase 4
• First received: February 28, 2017
• Last updated: January 29, 2018
• Start date: January 1, 2017
• Est. completion date: January 10, 2018

Study information

• Verified date: January 2018
• Source: Institute of Liver and Biliary Sciences, India
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 111
• Est. completion date: January 10, 2018
• Est. primary completion date: January 10, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adult patients (>18 years )

2. Refractory septic shock (Noradrenaline >0.5mcg/kg/mt )

Exclusion Criteria:

1. Declined consent

2. Pregnancy

3. Less than 18 years old

4. Immunosuppressant patients (e.g. on steroid medication, active anti-cancer chemotherapeutic agent, etc.)

5. Glucose-6-phosphate dehydrogenase deficiency

6. Medication of Serotonin modulator/SSRI

7. Pre-existing Pulmonary Hypertension

8. CKD-Stage IV/V

9. Patients with GI bleed

10. Patients on DNR

11. Patients declared Brain dead

Related Conditions & MeSH terms

• Cirrhosis, Liver
• Fibrosis
• Liver Cirrhosis
• Refractory Shock
• Septic Shock
• Shock
• Shock, Septic
• Vasoplegia

Intervention

Drug:
• Methylene Blue

Locations

Country	Name	City	State
India	Liver Coma ICU, Institute of Liver and Biliary Sciences	New Delhi	Delhi

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Liver and Biliary Sciences, India

Country where clinical trial is conducted

India, 

References & Publications (5)

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. Review. — View Citation

Juffermans 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 — View Citation

Kirov MY, Evgenov OV, Evgenov NV, Egorina EM, Sovershaev MA, Sveinbjørnsson 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. — View Citation

Memis 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. — View Citation

Park 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival in both groups		2 days
Secondary	Systemic Vascular Resistance	Change in SVR	6 hours
Secondary	Mean Arterial Pressure	Improvement in MAP	6 hours
Secondary	Decrease of vasopressor dose of 20 percent from time of start of test drug.	Effect on decreasing vasopressor doses	6 hours