VANISH Trial

JAMA

August 2, 2016

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

What was the research question?

  • Does early vasopressin use, titrated up to 0.06 U/min improve kidney outcomes compared with norepinephrine in patients with septic shock requiring vasopressors?


How did they do it?

  • A factorial (2X2), double-blind, randomized clinical trial with 1:1:1:1 assignment in 18 Intensive Care Units in the United Kingdome

  • Included adult patients who had septic shock requiring vasopressors despite fluid resuscitation within a maximum of 6 hours after the onset of shock.

  • 409 patients were randomly allocated to vasopressin (titrated up to 0.06 U/min) and hydrocortisone (n = 101), vasopressin and placebo (n = 104), norepinephrine and hydrocortisone (n = 101), or norepinephrine and placebo (n = 103).

  • The primary outcome was kidney failure–free days during the 28-day period after randomization.

  • Secondary outcomes were rates of renal replacement therapy, mortality, and serious adverse events were secondary outcomes.


What did they find?

  • Rate of survivors who never developed kidney failure in the vasopressin group was not statistically different than those in the vasopressin group (57.0% vs, 59.2%, difference, −2.3% [95% CI, −13.0% to 8.5%]).

  • The median number of kidney failure–free days for patients who did not survive, who experienced kidney failure, or both was 9 days in the vasopressin group and 13 days in the norepinephrine group (difference, −4 days [95% CI, −11 to 5]).

  • There was less use of renal replacement therapy in the vasopressin group than in the norepinephrine group (25.4% vs. 35.3%; difference, −9.9% [95% CI, −19.3% to −0.6%]).

  • There was no significant difference in mortality rates between groups.

  • 10.7% had a serious adverse event in the vasopressin group vs. 8.3% in the norepinephrine group (difference, 2.5% [95% CI, −3.3% to 8.2%]).


What does it mean?

  • Early use of vasopressin compared with norepinephrine did not improve the number of kidney failure–free days in adults with septic shock.

  • These findings do not support the use of vasopressin as a first line treatment replacing norepinephrine, however, the confidence interval included a potential clinically important benefit for vasopressin.

VANISH Trial