Protocol and Statistical Analysis Plan for the Vasopressin for Septic Shock Pragmatic (VASSPR) Cluster-Crossover Randomized Trial

TL;DR

This paper outlines a clinical trial to determine whether starting vasopressin at a lower or higher threshold improves survival in septic shock patients.

Contribution

The study introduces a pragmatic cluster-crossover trial design to compare vasopressin initiation thresholds in septic shock treatment.

Findings

The trial compares vasopressin initiation at 0.1 vs. 0.4 mg/kg/min norepinephrine equivalents.

The primary outcome is 28-day all-cause mortality in septic shock patients.

The protocol and statistical analysis plan are prespecified to ensure rigorous trial conduct.

Abstract

Guidelines recommend vasopressin as the preferred second-line vasopressor for treatment of septic shock. However, the optimal threshold for vasopressin initiation is unclear.

Does a treatment strategy using a lower or a higher threshold for initiation of vasopressin as a secondary vasopressor decrease the incidence of 28-day mortality for patients with septic shock?

The Vasopressin for Septic Shock Pragmatic (VASSPR) trial is a multicenter, open-label, cluster-randomized, multiple cluster-crossover pragmatic clinical trial being conducted in 13 hospitals in Utah and Idaho. The trial compares a strategy for septic shock management recommending initiation of fixed-dose vasopressin as a secondary vasopressor at a lower threshold (when the total dose of other vasopressors reaches 0.1 mg/kg/min norepinephrine equivalents [NEEs]) to a strategy initiating vasopressin at a higher threshold (when other vasopressors reach 0.4 mg/kg/min NEEs). All adult patients with septic shock at study hospitals are enrolled in the trial and assigned to the treatment strategy in place at the study hospital when and where they start vasopressor treatment for suspected or confirmed septic shock. Individual patient care, including adherence to the assigned vasopressin initiation strategy, occurs at the discretion of each patient’s treating clinicians. The primary outcome is 28-day all-cause mortality. The key secondary outcome is renal replacement therapy-free days to day 28.

This article describes the protocol and statistical analysis plan for the conduct and analysis of the VASSPR trial.

The VASSPR trial will provide important data to guide vasopressor management for patients with septic shock. Prespecification of the trial protocol and statistical analysis plan before completion of enrollment is important for rigorous trial conduct and reporting.

ClinicalTrials.gov; No.: NCT06217562; URL: www.clinicaltrials.gov

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