Evaluating in Cirrhotics With Refractory Vasoplegia the Effect of Methylene Blue

NCT03120637 | Completed Phase 4

• 1 other identifier: ILBS-Septic Shock-01
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Septic Shock; Vasoplegia; Cirrhosis, Liver; Refractory Shock

Keywords

Methylene Blue; Septic Shock; Vasoplegia; Cirrhosis

Outcome Measures

Primary Outcomes (1)

• Survival in both groups

  2 days

Secondary Outcomes (3)

• Systemic Vascular Resistance

  6 hours

• Mean Arterial Pressure

  6 hours

• Decrease of vasopressor dose of 20 percent from time of start of test drug.

  6 hours

Study Arms (2)

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

Drug: Methylene Blue

Standard Treatment

NO INTERVENTION

Interventions

Methylene Blue DRUG

Methylene Blue

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (\>18 years )
• Refractory septic shock (Noradrenaline \>0.5mcg/kg/mt )

You may not qualify if:

• 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
• Pre-existing Pulmonary Hypertension
• CKD-Stage IV/V
• Patients with GI bleed
• Patients on DNR
• Patients declared Brain dead

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India: lead

Study Sites (1)

Liver Coma ICU, Institute of Liver and Biliary Sciences

New Delhi, National Capital Territory of Delhi, 110070, India

Location

Related 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.

  PMID: 24151551 RESULT

• 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. doi: 10.3904/kjim.2005.20.2.123.

  PMID: 16134766 RESULT

• Kirov 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.

  PMID: 11588440 RESULT

• 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. doi: 10.1177/0310057X0203000606.

  PMID: 12500513 RESULT

• 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.niox.2010.01.006. Epub 2010 Jan 28.

  PMID: 20109575 RESULT

MeSH Terms

Conditions

Shock, Septic; Vasoplegia; Liver Cirrhosis; Shock; Fibrosis

Interventions

Methylene Blue

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Phenothiazines; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Karthik Ponnappan, MD

  Institute of Liver and Biliary Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2017
• First Posted: April 19, 2017
• Study Start: January 1, 2017
• Primary Completion: January 10, 2018
• Study Completion: January 10, 2018
• Last Updated: January 30, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)