Weaning Approaches for Vasopressin in Sepsis (WAVES)

Hospital Nossa Senhora da Conceicao

Status and phase: Enrolling; Phase 3

Conditions: Septic Shock

Treatments: Other: Titrated weaning of vasopressin.; Other: Abrupt weaning of vasopressin.

Study type: Interventional

Funder types: Other

Identifiers

NCT07067866

CAAE: 83246724.1.0000.5530

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 82 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

82 participants in 2 patient groups

Titrated group

Experimental group

Description:

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

Treatment:

Other: Titrated weaning of vasopressin.

Abrupt group

Active Comparator group

Description:

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

Treatment:

Other: Abrupt weaning of vasopressin.