What Should be the Next Vasopressor for Severe Septic Shock? Methylene Blue or Terlipressin

What Should be the Next Vasopressor for Severe Septic Shock Patients? Methylene Blue or Terlipressin

The ICU mortality rate of patients with septic shock was still high upto 54.1%.In first 6 hours of resuscitation, the goals of resuscitation in sepsis shock after adequate fluid resuscitation is MAP ≥65 mmHg. In refractory septic shock patient, prolong shock correlate with poor outcome due to multiple organ failure. Alternative vasopressor in septic shock with catecholamine resistance has been studied such as terlipressin, methylene blue

• Terlipressin (TP) mediate vasoconstriction via V1 receptors coupled to phospholipase C, and increases intracellular Ca2+ concentration
• Methylene blue (MB) directly inhibits nitric oxide synthase (NOS) by inhibit the enzyme guanylate cyclase (GC)

Study Overview

• Status: Unknown
• Conditions: Septic Shock; Refractory Shock
• Intervention / Treatment: Drug: Methylene Blue; Drug: Terlipressin

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: munthana sundusadee, md; Phone Number: 66639010178; Email: opal_janeway@hotmail.com

Study Locations

• Thailand
  • Bangkok, Thailand, 066
    • Recruiting
    • Ramathibodi Hospital
    • Contact: munthana sundusadee, md; Phone Number: 66639010178; Email: opal_janeway@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age >15 years old
• Diagnosis septic shock as SCCM/ACCP
• Refractory septic shock defined as hypotension although adequate fluid resuscitate and high dose vasopressor(NE >0.5 mcg/kg/min)
• Concent form

Exclusion Criteria:

• Known case G6PD deficiency
• Acute respiratory distress syndrome (ARDS)
• Hx of drug allergy MB, NE, terlipressin
• Hx of Raynaud's phenomenon, systemic sclerosis, PHT
• Known case coronary heart disease without treatment
• Current drug use serotonin reuptake inhibitors (SSRI), Serotonin and norepinephrine reuptake inhibitors (SNRIs)
• Reject to join project

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: A; standard care septic shock according sepsis bundles
Experimental: B; after defined refractory shock (adequate fluid resuscitation + add NE>0.5 mcg/kg/min) add Methylene blue 1 mg/kg iv drip then 2 hr later drip 0.5 mg/kg/hr*4 hr (intervention add on to standard care)	Drug: Methylene Blue; after defined refractory shock (need NE>0.5 mcg/kg/min) add Methylene blue 1 mg/kg iv drip then 2 hr later drip 0.5 mg/kg/hr*4 hr (intervention add on to standard care)
Experimental: C; after defined refractory shock (adequate fluid resuscitation + add NE>0.5 mcg/kg/min) add terlipressin 1 mg IV then repeated dose 20 min later if unstable BP (intervention add on to standard care)	Drug: Terlipressin; after defined refractory shock (need NE>0.5 mcg/kg/min) add terlipressin 1 mg IV then repeated dose 20 min later if unstable BP (intervention add on to standard care)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
mortality rate	7 days
time to wean of vasopressor	through complete weaning off vasopressor, an average of 24 hours
ICU duration	through out off indication need ICU care, an average of 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hemodynamic parameter: Mean arterial pressure (mmHg)	mmHg, A-line monitoring	every 30 min after start protocol up to 6 hr then every 1 hr up to 24 hours
hemodynamic parameter: lactate (mmol/l)	mmol/l	every 2 hr until 6 hr then every 4 hr until wean off vasopressor up to 24 hours
hemodynamic parameter: urine output (ml)	ml	every 2 hr until wean off vasopressor up to 24 hours

Collaborators and Investigators

• Sponsor: Ramathibodi Hospital
• Investigators: Study Chair: viratch tangsujaritvijit, MD, Mahidol University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: December 22, 2016
• First Submitted That Met QC Criteria: January 28, 2017
• First Posted (Estimate): January 31, 2017

Study Record Updates

• Last Update Posted (Actual): August 29, 2018
• Last Update Submitted That Met QC Criteria: August 28, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: terlipressin; methylene blue; refractory septic shock; catecholamine resistance septic shock
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Vasoconstrictor Agents; Methylene Blue; Terlipressin
• Other Study ID Numbers: ID 09-59-14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No