Design: Pragmatic cluster-randomised, cluster-crossover strategy trial (VASSPR)
Population: 3,959 adults with septic shock at 13 US hospitals
Primary outcome: 28-day mortality
Effect: 31.8% vs 33.0%; adjusted OR 0.98 (95% CI 0.87 to 1.06)

VASSPR assigned 13 hospitals to recommend adding fixed-dose vasopressin either at a lower noradrenaline-equivalent dose or at a higher one, switching strategy every month. Nearly 4,000 patients with septic shock were included.

The strategies did separate in practice: vasopressin started at a median of 0.14 versus 0.34 µg/kg/min. But mortality at 28 days and kidney outcomes were similar.

The trial tested a hospital policy rather than individual patient decisions, so it does not rule out benefit in particular patients. It does suggest that the timing of vasopressin is not a major lever on survival.

Lower-threshold hospitals added vasopressin at 0.1 µg/kg/min of noradrenaline equivalent; higher-threshold hospitals at 0.4.
Mortality was 31.8% with the lower threshold and 33.0% with the higher.
Days free of kidney replacement therapy were the same.
More patients received vasopressin under the lower threshold (68% vs 43%).
Vasopressin cost and supply vary in India; this trial removes pressure to use it early.

Why it matters

Many protocols push early vasopressin on the strength of physiology and earlier trials, and this large pragmatic trial found no mortality gain from doing so.

The statistics, in plain English

An odds ratio of 0.98 with an interval from 0.87 to 1.06 crosses 1, so there is no evidence of a difference. The interval is narrow, which means a large effect in either direction is unlikely.