Weaning Approaches for Vasopressin in Sepsis

NCT07067866 | Recruiting Phase 3

• 1 other identifier: CAAE: 83246724.1.0000.5530
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, we aim to evaluate the incidence of hypotension during vasopressin weaning by comparing two methods - titrated reduction versus abrupt withdrawal - through the conduct of a randomized clinical trial.

Conditions

Septic Shock

Keywords

vasopressin; septic shock; vasopressor weaning

Outcome Measures

Primary Outcomes (1)

• Hypotension within the first 24 hours

  Incidence of hypotension with clinical repercussions within the first 24 hours after titrated reduction or abrupt withdrawal of vasopressin. Definition of hypotension with clinical repercussions: mean arterial pressure \< 60 mmHg, leading to: * administration of crystalloid/colloid bolus and/or * increase in norepinephrine dose and/or * reinitiation or increase in vasopressin dose.

  24 hours

Secondary Outcomes (9)

• Hypotension stratified according to vasopressin duration

  24 hours

• Hypotension within the first hour

  First hour

• Vasopressor-free days

  7 days

• Vasopressin-free days

  7 days

• Renal replacement therapy

  7 days

Study Arms (2)

Titrated group

EXPERIMENTAL

The titrated group will follow the vasopressin weaning protocol used in the DOVSS study (reduction of 0.01 U/min per hour).

Other: Titrated weaning of vasopressin.

Abrupt group

ACTIVE COMPARATOR

The abrupt group will discontinue the vasopressin infusion at the time of randomization, without dose titration.

Other: Abrupt weaning of vasopressin.

Interventions

Titrated weaning of vasopressin. OTHER

The titrated group will follow the vasopressin weaning protocol used in the DOVSS study (reduction of 0.01 U/min per hour).

Titrated group

Abrupt weaning of vasopressin. OTHER

The abrupt group will discontinue the vasopressin infusion at the time of randomization, without dose titration.

Abrupt group

Eligibility Criteria

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

You may qualify if:

• Age over 18 years
• Admitted to the Intensive Care Unit
• Patients with vasopressor dependent sepsis
• Receiving combined norepinephrine and vasopressin therapy

You may not qualify if:

• Withdrawal/reduction of vasopressin related to a plan of treatment limitation or palliative care
• Withdrawal/reduction of vasopressin associated with the initiation of adrenaline or any other vasopressor

Sponsors & Collaborators

• Hospital Nossa Senhora da Conceicao: lead

Study Sites (1)

Hospital Nossa Senhora da Conceição

Porto Alegre, Rio Grande do Sul, 91350200, Brazil

RECRUITING

Related Publications (13)

• Murata J, Buckley M, Lehn J, Agarwal SK, Stevenson B, Martinez B, MacLaren R. Incidence of Hypotension Associated With Two Different Vasopressin Discontinuation Strategies in the Recovery Phase of Septic Shock. J Pharm Pract. 2023 Aug;36(4):830-838. doi: 10.1177/08971900221078270. Epub 2022 Mar 25.

  PMID: 35331049 RESULT

• Lam SW, Sacha GL, Duggal A, Reddy AJ, Bauer SR. Abrupt Discontinuation Versus Down-Titration of Vasopressin in Patients Recovering from Septic Shock. Shock. 2021 Feb 1;55(2):210-214. doi: 10.1097/SHK.0000000000001609.

  PMID: 32842024 RESULT

• Der-Nigoghossian C, Hammond DA, Ammar MA. Narrative Review of Controversies Involving Vasopressin Use in Septic Shock and Practical Considerations. Ann Pharmacother. 2020 Jul;54(7):706-714. doi: 10.1177/1060028020901521. Epub 2020 Jan 20.

  PMID: 31958982 RESULT

• Jeon K, Song JU, Chung CR, Yang JH, Suh GY. Incidence of hypotension according to the discontinuation order of vasopressors in the management of septic shock: a prospective randomized trial (DOVSS). Crit Care. 2018 May 21;22(1):131. doi: 10.1186/s13054-018-2034-9.

  PMID: 29784057 RESULT

• Sacha GL, Lam SW, Duggal A, Torbic H, Reddy AJ, Bauer SR. Hypotension Risk Based on Vasoactive Agent Discontinuation Order in Patients in the Recovery Phase of Septic Shock. Pharmacotherapy. 2018 Mar;38(3):319-326. doi: 10.1002/phar.2082. Epub 2018 Feb 8.

  PMID: 29328496 RESULT

• Hammond DA, Painter JT, Meena N. Incidence of Clinically Significant Hypotension Stratified by Vasopressin Duration. J Intensive Care Med. 2019 Jan;34(1):77-78. doi: 10.1177/0885066617745809. No abstract available.

  PMID: 30798676 RESULT

• Landry DW, Levin HR, Gallant EM, Ashton RC Jr, Seo S, D'Alessandro D, Oz MC, Oliver JA. Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation. 1997 Mar 4;95(5):1122-5. doi: 10.1161/01.cir.95.5.1122.

  PMID: 9054839 RESULT

• Bissell BD, Magee C, Moran P, Bastin MLT, Flannery AH. Hemodynamic Instability Secondary to Vasopressin Withdrawal in Septic Shock. J Intensive Care Med. 2019 Sep;34(9):761-765. doi: 10.1177/0885066617716396. Epub 2017 Jul 28.

  PMID: 28750598 RESULT

• Bauer SR, Aloi JJ, Ahrens CL, Yeh JY, Culver DA, Reddy AJ. Discontinuation of vasopressin before norepinephrine increases the incidence of hypotension in patients recovering from septic shock: a retrospective cohort study. J Crit Care. 2010 Jun;25(2):362.e7-362.e11. doi: 10.1016/j.jcrc.2009.10.005.

  PMID: 19926252 RESULT

• De Backer D, Deutschman CS, Hellman J, Myatra SN, Ostermann M, Prescott HC, Talmor D, Antonelli M, Pontes Azevedo LC, Bauer SR, Kissoon N, Loeches IM, Nunnally M, Tissieres P, Vieillard-Baron A, Coopersmith CM; Surviving Sepsis Campaign Research Committee. Surviving Sepsis Campaign Research Priorities 2023. Crit Care Med. 2024 Feb 1;52(2):268-296. doi: 10.1097/CCM.0000000000006135. Epub 2024 Jan 19.

  PMID: 38240508 RESULT

• Teboul JL, Duranteau J, Russell JA. Intensive care medicine in 2050: vasopressors in sepsis. Intensive Care Med. 2018 Jul;44(7):1130-1132. doi: 10.1007/s00134-017-4909-7. Epub 2017 Aug 31. No abstract available.

  PMID: 28861671 RESULT

• Leone M, Einav S, Antonucci E, Depret F, Lakbar I, Martin-Loeches I, Wieruszewski PM, Myatra SN, Khanna AK. Multimodal strategy to counteract vasodilation in septic shock. Anaesth Crit Care Pain Med. 2023 Jun;42(3):101193. doi: 10.1016/j.accpm.2023.101193. Epub 2023 Jan 5.

  PMID: 36621622 RESULT

• Hammond DA, Rech MA, Daley MJ, Devlin JW, Hodge EK, Kooda KJ, Lat I, Personett HA, Roberts R, Sacha G, Stollings JL, Swanson JM, Bauer SR. Perceptions regarding vasopressin use and practices in septic shock, and cost containment strategies. J Am Coll Clin Pharm. 2019 Jun;2(3):257-267. doi: 10.1002/jac5.1079. Epub 2019 Jan 24.

  PMID: 38213315 RESULT

MeSH Terms

Conditions

Shock, Septic; Diabetes Insipidus

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pituitary Diseases; Endocrine System Diseases

Study Officials

• Cássio Mallmann, Critical Care Physician, MS

  Hospital Nossa Senhora da Conceicao

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wagner Luis Nedel, Critical Care Physician, PhD

CONTACT

55 51 999547554; wagnernedel@gmail.com

Rafael Barberena Moraes, Critical Care Physician, PhD

CONTACT

55 51 996971855; rbmoraes@hcpa.edu.br

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Critical Care Physician, MS

Study Record Dates

• First Submitted: July 6, 2025
• First Posted: July 16, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): October 1, 2028
• Last Updated: January 2, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)