Current partner codePEPTIDESDE
NCT04339868·Phase 2·INTERVENTIONAL

Terlipressin for Refractory Septic Shock

Status

Unknown

Phase

Phase 2

Enrollment

130

Locations

1

Results

Not posted

Publications

3

Study summary

What the protocol is testing.

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.

Full detailed 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.

Interventions

Treatment arms and agents.

DRUG

Terlipressin

Terlipressin (20-100 mcg/hr) plus norepinephrine and/or epinephrine

DRUG

Placebo

0.9% NaCl plus norepinephrine and/or epinephrine

Timeline

From registration to results.

  1. First posted

    Apr 9, 2020

  2. Study start

    Apr 3, 2020

  3. Primary completion

    Mar 31, 2025

  4. Study completion

    Jul 31, 2025

  5. Results posted

    Not reported

  6. Registry updated

    Sep 24, 2021

Outcomes

What the study measures.

Primary outcomes

Achieve target blood pressure with low dose adrenergic agents

Time frame · 6 hours after initiate study drug

Achieve target mean arterial blood pressure 65 millimeter mercury or more with norepinephrine and/or epinephrine dose 0.2 mcg/kg/min or lower

Secondary outcomes

28 day mortality

Time frame · 28 days

Proportion of patient who dead before 28 days after enrollment

Mean arterial blood pressure

Time frame · 72 hours

Mean arterial blood pressure after initiate study drug

Hospital mortality

Time frame · 90 days

Proportion of patient who dead before hospital discharge after enrollment

ICU mortality

Time frame · 90 days

Proportion of patient who dead before ICU discharge after enrollment

Eligibility

Who can take part.

Minimum age
18 Years
Maximum age
Not reported
Sex
ALL
Healthy volunteers
No

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 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 7\. 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. Evidence of left ventricular ejection fraction (LVEF) \< 35% 12. Acute coronary syndrome within 72 hours 13. Severe valvular heart disease 14. Documented life-threatening tachyarrhythmia before enrollment 15. Diagnosis of acute mesenteric ischemia before enrollment 16. Previous diagnosis of Raynaud's phenomenon 17. Known peripheral arterial disease 18. Refuse to sign the informed consent by patient or representative

Study locations

1 registered sites.

Thailand. Showing up to 24 locations stored in the fast local snapshot.

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

Bangkok, Thailand

Publications

Results and literature.

PMID 28101605Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18.PMID 26903338Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.PMID 30704260Permpikul C, Tongyoo S, Viarasilpa T, Trainarongsakul T, Chakorn T, Udompanturak S. Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER). A Randomized Trial. Am J Respir Crit Care Med. 2019 May 1;199(9):1097-1105. doi: 10.1164/rccm.201806-1034OC.

Primary links

Continue at the source.

Related trials

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