Efficacy of the Use of Vasopressin as a Primary Vasoconstrictor in Critically Ill Patients

NCT06265259 | Recruiting Phase 4

• 1 other identifier: 31-05-2023/25481
• Study Type: interventional
• Target: 145
• Locations: 1 country
• Sites: 1

Brief Summary

Current guidelines recommend the inititaion of noradrenaline and if shock is refractory, then vasopressin should be administered. Data indicate that the earlier use of vasopressin may improve survival. Two large randomized controlled trial failed to prove a survival benefit from the early use of vasopressin. The present study will investigate the effect of an early initiation protocol of vasopressin (as the first vasoconstrictor drug) on the degree of multiorgan failure improvement and also on the course of sepsis (if in septic patients) versus early initiation of noradrenaline as first vasoconstrictor drug in hemodynamically unstable patients.

Conditions

Circulatory Shock

Keywords

noradrenaline; vasopressin; shock; multiorgan failure; SOFA score

Outcome Measures

Primary Outcomes (1)

• Multiorgan failure improvement assessment

  Sequential Organ Failure Assessment score (min value 0, maximum value 24, with higher scores indicating worse patient status)

  10 days

Secondary Outcomes (25)

• Sepsis course

  10 days

• Sepsis course

  10 days

• Sepsis course

  10 days

• Duration of administration of vasoconstrictors

  10 days

• laboratory tests

  28 days

Study Arms (2)

Vasopresin Group

EXPERIMENTAL

Initiation of vasopressin as the first vasoactive agent (1 amp in 50 mlN/S) up to a maximum dose of 0.03 IU/min (2.3 ml/h). If the patient has MAP \<65 mmHg then noradrenaline will be started.

Drug: Initiation of vasopressine as a first vasoconstrictive drug

Noradrenaline group

ACTIVE COMPARATOR

Initiation of noradrenaline first, up to 0,5 mcg/kg/min. If the patient has MAP \<65 mmHg vasopressin will be started (maximum dose of 0.03 IU/min (2.3ml/h)\]. If If the patient has MAP \<65 mmHg, noradrenaline will be further escalated.

Drug: Initiation of noradrenaline as a first vasoconstrictive drug

Interventions

Initiation of vasopressine as a first vasoconstrictive drug DRUG

The group (arm 1) where vasopressin (1 amp in 50 mlN/S) (1st vasoconstrictor) will be administered first up to a maximum dose of 0.03 IU/min (2.3 ml/h) for the treatment of hemodynamic instability. Then, if the patient remains unstable, noradrenaline (2nd vasoconstrictor) will be started. The dose of vasopressin will not be increased further than the above mentioned limit.

Also known as: Vasopressine, Empressin

Vasopresin Group

Initiation of noradrenaline as a first vasoconstrictive drug DRUG

ii. In the group (arm 2) where the treatment of haemodynamic instability will be performed by first administering noradrenaline (1st vasoconstrictor) up to 0,5 mcg/kg/min and then, if the patient is still unstable, adding vasopressin (2nd vasoconstrictor) at a maximum dose of 0.03 IU/min (2.3ml/h). If haemodynamic instability persists, treatment will involve further increase of the noradrenaline dose.

Also known as: Noradren, Levophed

Noradrenaline group

Eligibility Criteria

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

You may qualify if:

• Shock (mean arterial pressure \<65 mmHg) after initial resuscitation with fluids

You may not qualify if:

• Patients under 18 years of age.
• Known heart failure (ejection fraction \&lt;35%)
• Recent acute myocardial infarction
• Pulmonary embolism

Sponsors & Collaborators

• University of Thessaly: lead

Study Sites (1)

General University Hospital of Larissa, Intensive Care Unit

Larissa, Thessaly, 41110, Greece

RECRUITING

Related Publications (7)

• Rydz AC, Elefritz JL, Conroy M, Disney KA, Miller CJ, Porter K, Doepker BA. EARLY INITIATION OF VASOPRESSIN REDUCES ORGAN FAILURE AND MORTALITY IN SEPTIC SHOCK. Shock. 2022 Oct 1;58(4):269-274. doi: 10.1097/SHK.0000000000001978. Epub 2022 Aug 16.

  PMID: 36018257 RESULT

• Hammond DA, Cullen J, Painter JT, McCain K, Clem OA, Brotherton AL, Chopra D, Meena N. Efficacy and Safety of the Early Addition of Vasopressin to Norepinephrine in Septic Shock. J Intensive Care Med. 2019 Nov-Dec;34(11-12):910-916. doi: 10.1177/0885066617725255. Epub 2017 Aug 18.

  PMID: 28820036 RESULT

• Sharshar T, Blanchard A, Paillard M, Raphael JC, Gajdos P, Annane D. Circulating vasopressin levels in septic shock. Crit Care Med. 2003 Jun;31(6):1752-8. doi: 10.1097/01.CCM.0000063046.82359.4A.

  PMID: 12794416 RESULT

• Russell JA, Walley KR, Singer J, Gordon AC, Hebert PC, Cooper DJ, Holmes CL, Mehta S, Granton JT, Storms MM, Cook DJ, Presneill JJ, Ayers D; VASST Investigators. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008 Feb 28;358(9):877-87. doi: 10.1056/NEJMoa067373.

  PMID: 18305265 RESULT

• Gordon AC, Mason AJ, Thirunavukkarasu N, Perkins GD, Cecconi M, Cepkova M, Pogson DG, Aya HD, Anjum A, Frazier GJ, Santhakumaran S, Ashby D, Brett SJ; VANISH Investigators. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial. JAMA. 2016 Aug 2;316(5):509-18. doi: 10.1001/jama.2016.10485.

  PMID: 27483065 RESULT

• Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Hylander Moller M, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021 Nov 1;49(11):e1063-e1143. doi: 10.1097/CCM.0000000000005337. No abstract available.

  PMID: 34605781 RESULT

• Hammond DA, Ficek OA, Painter JT, McCain K, Cullen J, Brotherton AL, Kakkera K, Chopra D, Meena N. Prospective Open-label Trial of Early Concomitant Vasopressin and Norepinephrine Therapy versus Initial Norepinephrine Monotherapy in Septic Shock. Pharmacotherapy. 2018 May;38(5):531-538. doi: 10.1002/phar.2105. Epub 2018 Apr 30.

  PMID: 29600824 RESULT

MeSH Terms

Conditions

Shock; Diabetes Insipidus; Multiple Organ Failure

Interventions

Norepinephrine

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pituitary Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Central Study Contacts

Vasiliki Tsolaki, PhD, MD

CONTACT

00306972804419; vasotsolaki@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 2, 2024
• First Posted: February 20, 2024
• Study Start: December 15, 2023
• Primary Completion: December 31, 2025
• Study Completion: January 31, 2026
• Last Updated: March 6, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)