Effect of Vasopressin Initiation Threshold on Septic Shock Mortality: The VASSPR Cluster Crossover Randomized Strategy Trial
Authors' conclusion
In this large, pragmatic clinical trial comparing the effectiveness of 2 hospital-level strategies for second-line vasopressor management in septic shock, a strategy recommending initiation of vasopressin at a lower dose of other vasopressors did not reduce 28-day mortality compared with a strategy recommending vasopressin initiation at a higher dose of other vasopressors.
Study context
- Population
- Adult patients receiving vasopressors for septic shock at hospitals in Idaho and Utah, February 1, 2024, to July 31, 2025unique patients with septic shock · lower-threshold strategy 1,975 · higher-threshold strategy 1,984
- Participants
- 3,959 patients
- Comparison
- Lower-threshold strategy vs higher-threshold strategy
- Lower-threshold strategyn = 1,975
- Higher-threshold strategyn = 1,984
- Primary endpoint
- 28-day mortality
- Follow-up
- 28 days
Methodological details13 hospitals, monthly crossover
- 13 hospitals
- Monthly crossover
Primary result
As reported in the abstract
Adjusted marginal odds ratio (95% CI)P value
Lower-threshold strategy vs higher-threshold strategy
0.98(0.87–1.06)
P = 0.62Adjusted risk difference, percentage points (95% CI)
Lower-threshold strategy vs higher-threshold strategy
−0.4(−2.7 to 1.3)
Secondary outcomes
Median, days
| Outcome | Lower-threshold strategy | Higher-threshold strategy | Adjusted marginal odds ratio (95% CI) | |
|---|---|---|---|---|
| Kidney replacement therapy-free days through day 28 (key secondary outcome) | 29 (IQR −1–29) | 29 (IQR −1–29) | 1.01 (0.91–1.14) | |
| 0.512Adjusted marginal odds ratio (log scale) |
Maximum vasopressor dose received prior to vasopressin initiation (process)
- Vasopressin received, among patients with maximum vasopressor dose ≥0.07 µg/kg/min of norepinephrine or equivalent (process): lower-threshold strategy (of those with maximum vasopressor dose ≥0.07 µg/kg/min) 68.0%
- Vasopressin received, among patients with maximum vasopressor dose ≥0.07 µg/kg/min of norepinephrine or equivalent (process): higher-threshold strategy (of those with maximum vasopressor dose ≥0.07 µg/kg/min) 42.7%
Original publication
Effect of Vasopressin Initiation Threshold on Septic Shock Mortality: The VASSPR Cluster Crossover Randomized Strategy Trial. JAMA. Published 14 October 2026. doi:10.
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