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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04339868
Other study ID # Si 049/2020
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date April 3, 2020
Est. completion date July 31, 2025

Study information

Verified date September 2021
Source Mahidol University
Contact Surat Tongyoo, MD
Phone 0820137771
Email surat.ton@mahidol.ac.th
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 130
Est. completion date July 31, 2025
Est. primary completion date March 31, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 Design


Intervention

Drug:
Terlipressin
Terlipressin (20-100 mcg/hr) plus norepinephrine and/or epinephrine
Placebo
0.9% NaCl plus norepinephrine and/or epinephrine

Locations

Country Name City State
Thailand Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University Bangkok

Sponsors (1)

Lead Sponsor Collaborator
Mahidol University

Country where clinical trial is conducted

Thailand, 

References & Publications (3)

Permpikul 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.201806-10 — View Citation

Rhodes 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 — View Citation

Singer 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 C — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Achieve target blood pressure with low dose adrenergic agents Achieve target mean arterial blood pressure 65 millimeter mercury or more with norepinephrine and/or epinephrine dose 0.2 mcg/kg/min or lower 6 hours after initiate study drug
Secondary 28 day mortality Proportion of patient who dead before 28 days after enrollment 28 days
Secondary Mean arterial blood pressure Mean arterial blood pressure after initiate study drug 72 hours
Secondary Hospital mortality Proportion of patient who dead before hospital discharge after enrollment 90 days
Secondary ICU mortality Proportion of patient who dead before ICU discharge after enrollment 90 days
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