Weaning Approaches for Vasopressin in Sepsis

Not Applicable

Not yet recruiting

• Conditions: Septic Shock

• Registration Number: NCT07067866
• Lead Sponsor: Hospital Nossa Senhora da Conceicao

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.

Detailed 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, Lam et al. published the first study 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, Murata et al. published another retrospective observational study also 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.

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-06
• Study First Submitted QC: 2025-07-06
• Last Update Submitted: 2025-07-06
• Study First Posted: 2025-07-16
• Last Update Posted: 2025-07-16
• Study Start: 2025-10-01
• Primary Completion: 2027-12-31
• Study Completion: 2028-10-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 82

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Hypotension within the first 24 hours	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 Outcome Measures

Name	Time	Method
Hypotension stratified according to vasopressin duration	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.
Hypotension within the first hour	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.
Vasopressor-free days	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.
Vasopressin-free days	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.
Renal replacement therapy	7 days	Initiation of hemodialysis between randomization and day 7, excluding chronic dialysis patients.
Cardiac arrhythmias	7 days	Incidence of arrhythmias with hemodynamic consequences between randomization and day 7, defined as hemodynamic deterioration requiring electrical or chemical cardioversion.
ICU-free days	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.
Ischemic events	28 days	Occurrence of mesenteric ischemia, ischemic stroke, digital ischemia and acute coronary syndrome between randomization and day 28.
All-cause mortality	28 days	All-cause mortality within 28 days after randomization.