Terlipressin for Refractory Septic Shock

Last updated: September 23, 2021
Sponsor: Mahidol University
Overall Status: Active - Recruiting

Phase

2

Condition

Sepsis And Septicemia

Low Blood Pressure (Hypotension)

Treatment

N/A

Clinical Study ID

NCT04339868
Si 049/2020
  • Ages > 18
  • All Genders

Study Summary

Norepinephrine was recommended as the first vasopressor for septic shock resuscitation.

For the patient who did not response to high dose norepinephrine, epinephrine was recommended.

Vasopressin was also recommended as an alternative vasopressor, in case patient did not response to norepinephrine and or epinephrine.

Terlipressin, a selective V1 receptor binding with long half life, was reported that it main action is to increase blood pressure via the different mechanism from norepinephrine and epinephrine.

To use terlipressin, combine with norepinephrine and or epinephrine among refractory septic shock, could decrease the usage dose of norepinephrine and epinephrine as well as lower the side effects of too high adrenergic stimuli.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Septic shock according to Sepsis-3 definition
  • Evidence of adequate fluid
  • Received norepinephrine 0.2 mcg/kg/min or more
  • Received norepinephrine plus epinephrine (any dose)
  • Mean arterial lower than 65 mmHg or lactate > 2 mmol/liter

Exclusion

Exclusion Criteria:

  1. Septic shock diagnosis > 48 hours before
  2. Receive intravenous fluid < 30 mL/kg before enrollment
  3. Do-not-resuscitation and terminally ill
  4. Refractory to treatment malignancy
  5. Pregnancy
  6. Chronic renal failure stage 5 with no plan for long term renal replacement therapy 8.Cirrhosis child C 9. Cardiogenic shock 10. Acute decompensated heart failure 11. Evidenceof left ventricular ejection fraction (LVEF) < 35% 12. Acute coronary syndrome within 72hours 13. Severe valvular heart disease 14. Documented life-threatening tachyarrhythmiabefore enrollment 15. Diagnosis of acute mesenteric ischemia before enrollment 16. Previousdiagnosis of Raynaud's phenomenon 17. Known peripheral arterial disease 18. Refuse to signthe informed consent by patient or representative

Study Design

Total Participants: 130
Study Start date:
April 03, 2020
Estimated Completion Date:
July 31, 2025

Study Description

Norepinephrine was recommended as the first vasopressor for septic shock resuscitation.

For the patient who did not response to high dose norepinephrine, epinephrine was recommended.

Both norepinephrine and epinephrine action via the alpha adrenergic stimuli to increase vascular smooth muscle contraction, induced vasoconstriction and increase arterial blood pressure. It also action via beta adrenergic stimuli, to increase heart rate and myocardial contractility, then increase stroke volume and cardiac output.

Too much alpha and beta adrenergic stimulation, especially during received high dose norepinephrine and or epinephrine associated with vasoconstriction induce organs ischemia.

The most common organ ischemia included myocardial ischemia, bowel ischemia and limbs ischemia.

Cardiac arrhythmia was also the most common complication associated with high dose norepinephrine and or epinephrine.

Atrial fibrillation was the most common reported arrhythmia, however, fatal arrhythmia included ventricular fibrillation and tachycardia were also reported.

Vasopressin was recommended as an alternative vasopressor, in case patient did not response to norepinephrine and or epinephrine.

Terlipressin, a selective V1 receptor binding with long half life, was reported that it main action is to increase blood pressure via the different mechanism from norepinephrine and epinephrine.

To use terlipressin, combine with norepinephrine and or epinephrine among refractory septic shock, could decrease the usage dose of norepinephrine and epinephrine as well as lower the side effects of too high adrenergic stimuli.

The benefit effect of terlipressin could be demonstrated when prescribe among the septic shock patients who required high dose of adrenergic vasoactive agents.

Terlipressin plus norepinephrine and or epinephrine could maintain or even improve blood pressure and tissue perfusion with lower fatal side effects than norepinephrine and or epinephrine without terlipressin.

Connect with a study center

  • Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University

    Bangkok, 10700
    Thailand

    Active - Recruiting

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