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

Mahidol University

Status and phase: Unknown; Phase 3

Conditions: Refractory Shock; Septic Shock

Treatments: Drug: Terlipressin; Drug: Methylene Blue

Study type: Interventional

Funder types: Other

Identifiers

NCT03038503

ID 09-59-14

Details and patient eligibility

About

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)

Enrollment: 60 estimated patients

Sex: All

Ages: 15+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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60 participants in 3 patient groups

A

No Intervention group

Description:

standard care septic shock according sepsis bundles

B

Experimental group

Description:

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)

Treatment:

Drug: Methylene Blue

C

Experimental group

Description:

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)

Treatment:

Drug: Terlipressin