LandmarkRCT

VANISH

Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock

JAMA, 2016 · Multicenter, randomized, double-blind, 2x2 factorial trial (vasopressor type and hydrocortisone).

Clinical question

Does using vasopressin as an early, primary vasopressor (rather than adding it after norepinephrine) reduce kidney failure in septic shock?

Population: 409 adults with septic shock.
Intervention: Vasopressin (titrated first) as the primary vasopressor.
Comparator: Norepinephrine as the primary vasopressor.
Primary outcome: Kidney failure-free days during the 28 days after randomization.
Secondary outcomes: 28-day mortality.
Rates of serious adverse events.
Result: No significant difference in kidney failure-free days or mortality between early vasopressin and norepinephrine.

What the trial found

Using vasopressin as an early, primary vasopressor did not improve kidney failure-free days or reduce mortality compared with norepinephrine as the primary vasopressor.

Current guideline position

The 2026 Surviving Sepsis Campaign guideline suggests adding vasopressin specifically in patients with escalating norepinephrine requirements, a narrower indication than the early-primary-agent strategy this trial tested.

Clinical interpretation

VANISH tested vasopressin as an early, primary agent rather than as an add-on for norepinephrine-refractory shock, which is a different clinical question from how vasopressin is actually used in current practice — it does not argue against the current guideline-endorsed role of vasopressin as an adjunct in escalating norepinephrine requirements.

Limitations

Tested vasopressin as a primary/early agent, not the add-on-for-escalating-norepinephrine strategy that guidelines actually endorse.
Underpowered relative to the observed event rates for definitively excluding a smaller true effect.

Moderate certainty

Clinical Context & Relevant Topics (1)

Disease Reference

Septic Shock

The subset of sepsis with profound circulatory and cellular/metabolic abnormality — clinically identified by a vasopressor requirement to maintain MAP ≥ 65 mmHg plus lactate > 2 mmol/L despite adequate fluid resuscitation.

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