Early Versus Late Adjunctive Vasopressin in Septic Shock

Phase 4

Not yet recruiting

• Conditions: Sepsis; Septic Shock
• Interventions: Drug: vasopressin - early initiation; Drug: vasopressin - standard initiation

• Registration Number: NCT06709573
• Lead Sponsor: The Cleveland Clinic

Brief Summary

The goal of the CASPER-Pilot study is to develop clinical decision support (CDS) technology within Epic to randomize patients with septic shock to early versus standard of care vasopressin initiation. The primary aim of this study will be to test the hypothesis that CDS technology can be utilized to create two distinct cohorts of patients reflecting different times of vasopressin initiation based on norepinephrine dose requirements. Secondarily, this study will evaluate the proportion of patients whose norepinephrine dose at the time of vasopressin initiation is within the specified range for the intervention arm they were randomized to. Other outcomes of evaluation will include adherence to the developed CDS technology and comparison of clinical outcomes between the two treatment arms.

Detailed Description

Sepsis is a highly prevalent and morbid disease estimated to account for up to 20% of annual deaths globally. If not rapidly identified and intervened upon, patients with sepsis may progress to septic shock, which is associated with mortality rates up to 50%. Patients with septic shock have persistent hypotension requiring vasoactive agents to augment blood pressure despite fluid resuscitation. Norepinephrine is recommended first-line by the Surviving Sepsis Campaign (SSC) guidelines for patients with septic shock. If mean arterial pressure (MAP) remains inadequate on norepinephrine, vasopressin is suggested as the second-line adjunctive agent. Over 30% of patients with septic shock in the United States (US) receive adjunctive vasopressin, with use rising over time. Despite increased use over time, ideal patient selection and initiation timing for adjunctive vasopressin in the course of a patient's shock are not well elucidated. The 2021 iteration of the SSC guidelines note that initiating vasopressin when the patient requires between 0.25 and 0.5 mcg/kg/min of norepinephrine "seems sensible". Yet, many questions remain regarding the timing of vasopressin initiation. The goal of this proposal is to evaluate the timing of vasopressin initiation in patients with septic shock based on the norepinephrine requirements at the time of vasopressin initiation. This pilot study will attempt to develop CDS technology in which to answer this clinical question.

Study Timeline

• Study First Submitted: 2024-11-21
• Study First Submitted QC: 2024-11-26
• Study First Posted: 2024-11-29
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-10
• Last Update Posted: 2025-02-11
• Study Start: 2025-03-01
• Primary Completion: 2025-12-01
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• Age ≥ 18 Years
• Diagnosis of Septic Shock
• Admitted to Cleveland Clinic Main Campus Medical ICU
• Receiving continuous infusion of norepinephrine at a dose > 5 mcg/min at time of enrollment

Exclusion Criteria

• Administration of any other vasoactive agent other than norepinephrine at time of enrollment
• Initiation of vasopressin by provider outside of the context of study when NE < 10 mcg/min (before BPA firing)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Early Vasopressin Initiation	vasopressin - early initiation	Patients randomized to this arm will have a provider BPA fire prompting vasopressin initiation when the norepinephrine dose is between 10-20 mcg/min
Standard of Care Vasopressin Initiation	vasopressin - standard initiation	Patients randomized to this arm will have a provider BPA fire prompting vasopressin initiation when the norepinephrine dose is between 20-35 mcg/min

Primary Outcome Measures

Name	Time	Method
Norepinephrine-equivalent dose	Outcome evaluated on day of vasopressin initiation	The primary outcome is the norepinephrine-equivalent dose (in mcg/min) at the time of vasopressin initiation between patients who were randomized by CDS to early adjunctive vasopressin initiation compare to late adjunctive vasopressin initiation

Secondary Outcome Measures

Name	Time	Method
Proportion of patients within goal norepinephrine-equivalent dose range	Outcome evaluated on day of vasopressin initiation	This outcome will evaluate the overall proportion of patients enrolled in the trial whose norepinephrine dose at the time of vasopressin is within the goal range for the treatment group (\< 20 mcg/min for the early vasopressin group and \> 20 mcg for the standard of care vasopressin)

Trial Locations

Locations (1)

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States