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Evaluating in Cirrhotics With Refractory Vasoplegia the Effect of Methylene Blue (CRuMBS)

Primary Purpose

Septic Shock, Vasoplegia, Cirrhosis, Liver

Status
Completed
Phase
Phase 4
Locations
India
Study Type
Interventional
Intervention
Methylene Blue
Sponsored by
Institute of Liver and Biliary Sciences, India
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Septic Shock focused on measuring Methylene Blue, Septic Shock, Vasoplegia, Cirrhosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Liver Coma ICU, Institute of Liver and Biliary Sciences

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Methylene Blue

Standard Treatment

Arm Description

Methylene Blue intravenous route, 2 mg/kg Loading Dose over 30 minutes, followed by 0.5 mg/kg/hr for 6 hours

Outcomes

Primary Outcome Measures

Survival in both groups

Secondary Outcome Measures

Systemic Vascular Resistance
Change in SVR
Mean Arterial Pressure
Improvement in MAP
Decrease of vasopressor dose of 20 percent from time of start of test drug.
Effect on decreasing vasopressor doses

Full Information

First Posted
February 28, 2017
Last Updated
January 29, 2018
Sponsor
Institute of Liver and Biliary Sciences, India
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1. Study Identification

Unique Protocol Identification Number
NCT03120637
Brief Title
Evaluating in Cirrhotics With Refractory Vasoplegia the Effect of Methylene Blue
Acronym
CRuMBS
Official Title
Evaluating in Cirrhotics With Refractory Vasoplegia the Effect of Methylene Blue in Sepsis: A Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
January 1, 2017 (Actual)
Primary Completion Date
January 10, 2018 (Actual)
Study Completion Date
January 10, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institute of Liver and Biliary Sciences, India

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Septic Shock, Vasoplegia, Cirrhosis, Liver, Refractory Shock
Keywords
Methylene Blue, Septic Shock, Vasoplegia, Cirrhosis

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 4
Interventional Study Model
Sequential Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
111 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Methylene Blue
Arm Type
Experimental
Arm Description
Methylene Blue intravenous route, 2 mg/kg Loading Dose over 30 minutes, followed by 0.5 mg/kg/hr for 6 hours
Arm Title
Standard Treatment
Arm Type
No Intervention
Intervention Type
Drug
Intervention Name(s)
Methylene Blue
Primary Outcome Measure Information:
Title
Survival in both groups
Time Frame
2 days
Secondary Outcome Measure Information:
Title
Systemic Vascular Resistance
Description
Change in SVR
Time Frame
6 hours
Title
Mean Arterial Pressure
Description
Improvement in MAP
Time Frame
6 hours
Title
Decrease of vasopressor dose of 20 percent from time of start of test drug.
Description
Effect on decreasing vasopressor doses
Time Frame
6 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult patients (>18 years ) Refractory septic shock (Noradrenaline >0.5mcg/kg/mt ) Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karthik Ponnappan, MD
Organizational Affiliation
Institute of Liver and Biliary Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Liver Coma ICU, Institute of Liver and Biliary Sciences
City
New Delhi
State/Province
Delhi
ZIP/Postal Code
110070
Country
India

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
24151551
Citation
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.
Results Reference
result
PubMed Identifier
16134766
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. doi: 10.3904/kjim.2005.20.2.123.
Results Reference
result
PubMed Identifier
11588440
Citation
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.
Results Reference
result
PubMed Identifier
12500513
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. doi: 10.1177/0310057X0203000606.
Results Reference
result
PubMed Identifier
20109575
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.niox.2010.01.006. Epub 2010 Jan 28.
Results Reference
result

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Evaluating in Cirrhotics With Refractory Vasoplegia the Effect of Methylene Blue

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