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CompletedNCT03120637CRuMBSUpdated Jan 30, 2018

Evaluating in Cirrhotics With Refractory Vasoplegia the Effect of Methylene Blue

A Phase 4 interventional study of Methylene Blue in Septic Shock, Vasoplegia and Cirrhosis, Liver, sponsored by Institute of Liver and Biliary Sciences, India. Completed at 1 site in India. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-01-30.

Sponsored by Institute of Liver and Biliary Sciences, India · Phase 4, Interventional, and Supportive care

Phase
Phase 4
Study type
Interventional
Enrollment
111
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

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

Keywords

  • Methylene Blue
  • Septic Shock
  • Vasoplegia
  • Cirrhosis
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Adult patients (>18 years )
  2. Refractory septic shock (Noradrenaline >0.5mcg/kg/mt )

Exclusion criteria

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
04

Study design

Phase
Phase 4
Primary purpose
Supportive care
Allocation
Randomized
Intervention model
Sequential assignment
Masking
Double (Participant, Outcomes assessor)
Enrollment
111 participants (actual)

Study arms

  • Experimental
    Methylene Blue

    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

  • No intervention
    Standard Treatment

Interventions

  • DrugMethylene Blue
05

What researchers measure

Primary outcomes

  1. Survival in both groups

    Time frame: 2 days

Secondary outcomes

  1. Systemic Vascular Resistance

    Change in SVR

    Time frame: 6 hours

  2. Mean Arterial Pressure

    Improvement in MAP

    Time frame: 6 hours

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

    Effect on decreasing vasopressor doses

    Time frame: 6 hours

06

Study locations

1 site
  • Liver Coma ICU, Institute of Liver and Biliary Sciences
    New Delhi, Delhi 110070, India
07

References and documents

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 24151551 ↗
  • 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. PubMed 16134766 ↗
  • 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. PubMed 11588440 ↗
  • 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. PubMed 12500513 ↗
  • 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. PubMed 20109575 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03120637
Lead sponsor
Institute of Liver and Biliary Sciences, India
Responsible party
Sponsor
First posted
Apr 19, 2017
Start date
Jan 1, 2017
Primary completion
Jan 10, 2018
Completion
Jan 10, 2018
Last update
Jan 30, 2018

Study contacts

Karthik Ponnappan, MD
principal investigator · Institute of Liver and Biliary Sciences

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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