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

Phase 3

• Conditions: Septic Shock; Refractory Shock
• Interventions: Drug: Methylene Blue; Drug: Terlipressin

• Registration Number: NCT03038503
• Lead Sponsor: Ramathibodi Hospital

Brief Summary

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)

Detailed Description

Not available

Study Timeline

• Study Start: 2016-12
• Study First Submitted: 2016-12-22
• Study First Submitted QC: 2017-01-28
• Study First Posted: 2017-01-31
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-28
• Last Update Posted: 2018-08-29
• Primary Completion: 2018-12
• Study Completion: 2018-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
B	Methylene Blue	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)
C	Terlipressin	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)

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Ramathibodi hospital; 🇹🇭 Bangkok, Thailand