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NCT Number: NCT07067866

Weaning Approaches for Vasopressin in Sepsis

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hospital Nossa Senhora da Conceição

Porto Alegre, Rio Grande do Sul, 91350200, Brazil

Location status: Recruiting

About this study

Catecholamine infusions are usually tapered gradually in a titrated manner. However, little is known about how to manage adjunctive therapies such as vasopressin. While catecholamines have a short half-life (2-3 minutes), vasopressin's half-life ranges from 10 to 20 minutes. Although endogenous vasopressin levels are depleted in the early phase of shock, they are restored during recovery. Given its pharmacokinetic profile and the endogenous dynamics across different phases of shock, the optimal approach to vasopressin withdrawal - whether titrated or abrupt - remains unclear.

In 2021, a study was published comparing abrupt versus gradual vasopressin discontinuation. This was a retrospective observational study including 1,318 patients. Using ICU length of stay as the primary outcome, no significant difference was observed between groups (abrupt discontinuation: 7.9 days; gradual discontinuation: 7.3 days; p = 0.6). Similarly, there was no difference in the incidence of clinically significant hypotension (abrupt: 39.7%; gradual: 41.7%; p = 0.53). However, when stratifying patients based on whether catecholamine infusions were still ongoing at the time of vasopressin discontinuation, the results reversed in terms of ICU stay (abrupt: 9.2 days; gradual: 7.6 days), although this difference was not statistically significant (p = 0.24). In 2023, another retrospective observational study was published comparing abrupt versus gradual vasopressin withdrawal, including 74 patients. No difference was found in the incidence of clinically significant hypotension (abrupt: 57.1%; gradual: 52.3%; p = 0.68), nor in ICU length of stay. It is important to note, however, that in this cohort only patients who had already discontinued catecholamines prior to vasopressin withdrawal were included.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • 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

Treatment and study plan

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).

Abrupt weaning of vasopressin.

Other

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

Primary outcomes

  1. Hypotension within the first 24 hours

    Time frame: 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.

Secondary outcomes

  1. Hypotension stratified according to vasopressin duration

    Time frame: 24 hours

    Incidence of hypotension with clinical repercussions within the first 24 hours after titrated reduction or abrupt withdrawal of vasopressin, stratified according to vasopressin duration:

    < 48 hours

    ≥ 48 hours

    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.

  2. Hypotension within the first hour

    Time frame: First hour

    Incidence of hypotension with clinical repercussions within the first hour 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.

  3. Vasopressor-free days

    Time frame: 7 days

    Number of days a patient is alive and free of vasopressor between randomization and day 7. Non-survivors will be considered to have zero vasopressor-free days.

  4. Vasopressin-free days

    Time frame: 7 days

    Number of days a patient is alive and free of vasopressin between randomization and day 7. Non-survivors will be considered to have zero vasopressin-free days.

  5. Renal replacement therapy

    Time frame: 7 days

    Initiation of hemodialysis between randomization and day 7, excluding chronic dialysis patients.

  6. Cardiac arrhythmias

    Time frame: 7 days

    Incidence of arrhythmias with hemodynamic consequences between randomization and day 7, defined as hemodynamic deterioration requiring electrical or chemical cardioversion.

  7. ICU-free days

    Time frame: 28 days

    Number of days a patient is alive and outside the ICU between randomization and day 28. Non-survivors will be considered to have zero ICU-free days.

  8. Ischemic events

    Time frame: 28 days

    Occurrence of mesenteric ischemia, ischemic stroke, digital ischemia and acute coronary syndrome between randomization and day 28.

  9. All-cause mortality

    Time frame: 28 days

    All-cause mortality within 28 days after randomization.

Study contacts

Contact information is provided by the study sponsor or research team.

Rafael Barberena Moraes, Critical Care Physician, PhD

CONTACT

[email protected]

55 51 996971855

Wagner Luis Nedel, Critical Care Physician, PhD

CONTACT

[email protected]

55 51 999547554

Sponsors and collaborators

Lead sponsor

Hospital Nossa Senhora da Conceicao

Other

Registry information

Official study title

Weaning Approaches for Vasopressin in Sepsis - a Randomized Controlled Trial of Titrated Versus Abrupt Discontinuation During Stabilization of Septic Shock - WAVES Trial

Acronym: WAVES

Important dates

Study start
2025
Primary completion
2027
Study completion
2028
First posted
Jul 16, 2025
Registry last updated
Jan 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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