Terlipressin for Refractory Septic Shock

NCT04339868 | Unknown Phase 2

• 1 other identifier: Si 049/2020
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Septic Shock; Refractory Shock; Norepinephrine Adverse Reaction

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 28 day mortality

  28 days

• Mean arterial blood pressure

  72 hours

• Hospital mortality

  90 days

• ICU mortality

  90 days

Study Arms (2)

Terlipressin group

ACTIVE COMPARATOR

Terlipressin acetate 1 mg in 0.9% normal saline (NaCl) 50 mL (0.02 mg/mL) Initial dose 20 mcg/hr (1 mL/hr) titrate increase 1 mL/hr every 30 min to 100 mcg/hr (5 mg/hr) to keep mean arterial blood pressure (MAP) \> 65 mmHg If MAP \> 75 mmHg for \> 30 min, decrease epinephrine and norepinephrine until \< 0.15 mcg/kg/min, then decrease terlipressin until stop

Drug: Terlipressin

Placebo group

PLACEBO COMPARATOR

Placebo 0.9% NaCl 50 mL Initial dose 1 mL/hr titrate increase 1 mL/hr every 30 min to 5 mg/hr to keep mean arterial blood pressure (MAP) \> 65 mmHg If MAP \> 75 mmHg for \> 30 min, decrease epinephrine and norepinephrine until \< 0.15 mcg/kg/min, then decrease placebo until stop

Drug: Placebo

Interventions

Terlipressin DRUG

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

Terlipressin group

Placebo DRUG

0.9% NaCl plus norepinephrine and/or epinephrine

Placebo group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Septic shock diagnosis \> 48 hours before
• Receive intravenous fluid \< 30 mL/kg before enrollment
• Do-not-resuscitation and terminally ill
• Refractory to treatment malignancy
• Pregnancy
• \. 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

Sponsors & Collaborators

• Mahidol University: lead

Study Sites (1)

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

Bangkok, 10700, Thailand

RECRUITING

Related Publications (3)

• 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 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: 28101605 RESULT

• 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 Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.

  PMID: 26903338 RESULT

• 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.201806-1034OC.

  PMID: 30704260 RESULT

MeSH Terms

Conditions

Shock, Septic; Shock

Interventions

Terlipressin

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Lypressin; Vasopressins; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Surat Tongyoo, MD

  Mahidol University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Surat Tongyoo, MD

CONTACT

0820137771; surat.ton@mahidol.ac.th

Chawanee Chayakul, MD

CONTACT

080-440-1137; jingjaring@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Performed a randomization table before enrollment. Prepare the study drug receiving or placebo receiving according to sequential number derived from the randomization table and keep it in a conceal envelop. Prepare study drug and placebo by a pharmacist or an investigation nurse, according to the randomization table number, and keep both study drug and placebo in the identical containment which labeled by a sequential number. Once a patient was enrolled and informed was signed, then study drug or placebo was start according to sequential number.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Intervention arm: Terlipressin plus Norepinephrine and/or Epinephrine Controlled arm: Placebo plus Norepinephrine and/or Epinephrine for Treatment Refractory Septic Shock

Study Record Dates

• First Submitted: April 7, 2020
• First Posted: April 9, 2020
• Study Start: April 3, 2020
• Primary Completion: March 31, 2025
• Study Completion: July 31, 2025
• Last Updated: September 24, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: After complete enrollment and for 24 months
• Access Criteria: Please direct contact to the principle investigator

Locations

TH (1)