Early Versus Late Adjunctive Vasopressin in Septic Shock (CASPER-Pilot)

Clinical Decision Support Assistance to Randomize Patients to Early or Late Adjunctive Vasopressin in Septic Shock

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.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Septic Shock
• Intervention / Treatment: Drug: vasopressin - early initiation; Drug: vasopressin - standard initiation

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 Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Abhijit Duggal, MD; Phone Number: 216-444-4838; Email: duggala2@ccf.org
• Study Contact Backup: Name: Gretchen L. Sacha, PharmD; Phone Number: 216-379-4237; Email: sachag@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44095
      • Recruiting
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early Vasopressin 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	Drug: vasopressin - early initiation; BPA fires to provider prompting vasopressin initiation when the norepinephrine dose is between 10-20 mcg/min; Other Names: vasopressin
Active Comparator: Standard of Care Vasopressin 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	Drug: vasopressin - standard initiation; BPA fires to provider prompting vasopressin initiation when the norepinephrine dose is between 20-35 mcg/min; Other Names: vasopressin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Norepinephrine-equivalent dose	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	Outcome evaluated on day of vasopressin initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients within goal norepinephrine-equivalent dose range	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)	Outcome evaluated on day of vasopressin initiation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemodynamic Response	Compare rates of hemodynamic response to vasopressin initiation between patients who were randomized by CDS to early adjunctive vasopressin initiation compare to late adjunctive vasopressin initiation	6 hours after vasopressin initiation
ICU mortality	Compare ICU mortality between patients who were randomized by CDS to early adjunctive vasopressin initiation compare to late adjunctive vasopressin initiation	Through hospitalization admission
In-hospital mortality	Compare rates of in-hospital mortality between patients who were randomized by CDS to early adjunctive vasopressin initiation compare to late adjunctive vasopressin initiation	Through hospitalization admission
BPA response rates	Overall evaluate and describe BPA response: the proportion of patients who were initiated on vasopressin, time to vasopressin initiation after BPA firing, and provider documented rationale for not initiating vasopressin after BPA firing	between the time of study enrollment and vasopressin initiation

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Gretchen L. Sacha, PharmD, The Cleveland Clinic

Publications and helpful links

General Publications

• Sacha GL, Lam SW, Wang L, Duggal A, Reddy AJ, Bauer SR. Association of Catecholamine Dose, Lactate, and Shock Duration at Vasopressin Initiation With Mortality in Patients With Septic Shock. Crit Care Med. 2022 Apr 1;50(4):614-623. doi: 10.1097/CCM.0000000000005317.

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2025
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: November 21, 2024
• First Submitted That Met QC Criteria: November 26, 2024
• First Posted (Actual): November 29, 2024

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Septic Shock; Sepsis; Vasopressin; Vasopressors
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pituitary Diseases; Shock; Pathological Conditions, Signs and Symptoms; Sepsis; Shock, Septic; Diabetes Insipidus; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Pituitary Hormones, Posterior; Pituitary Hormones; Vasopressins
• Other Study ID Numbers: 24-547

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes