ATHOS-3
Trial question
What is the effect of angiotensin II in patients with vasodilatory shock who do not respond to high-dose vasopressors?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
39.4% female
60.6% male
N = 344
344 patients (126 female, 195 male)
Inclusion criteria: patients with vasodilatory shock who were receiving > 0.2 µg of norepinephrine per kg of body weight per minute or the equivalent dose of another vasopressor
Key exclusion criteria: burns > 20% of total body-surface area, acute coronary syndrome, bronchospasm, liver failure, mesenteric ischemia, active bleeding, AAA, or an absolute neutrophil count of < 1,000/mm², or venoarterial ECMO or treatment with high-dose corticosteroids
Interventions
N=163 angiotensin II (synthetic human angiotensin II, LJPC-501 infusion)
N=158 placebo (saline infusion)
Primary outcome
Percentage of patients achieving an elevation in blood pressure > 10 mmHg from baseline or an improvement to > 75 mmHg at 3 hours
69.9
23.4
69.9 %
52.4 %
35.0 %
17.5 %
0.0 %
Angiotensin II
Placebo
Significant increase ▲
NNT = 2
Significant increase in the percentage of patients achieving an elevation in BP > 10 mmHg from baseline or an improvement to > 75 mmHg at 3 hours (69.9% vs. 23.4%; OR 7.95, 95% CI 4.76 to 13.3)
Secondary outcomes
Significant increase in mean cardiovascular SOFA score reduction at 48 hours (1.75 vs. 1.28 ; AD 1.37 , 95% CI 0.33 to 2.41)
Safety outcomes
No significant differences in serious adverse events (60.7% vs. 67.1%) and death by day 28 (46% vs. 54%, p=0.12; HR 0.78, 95% CI 0.57-1.07).
Conclusion
In patients with vasodilatory shock who were receiving > 0.2 µg of norepinephrine per kg of body weight per minute or the equivalent dose of another vasopressor, angiotensin II was superior to placebo with respect to the percentage of patients achieving an elevation in BP > 10 mmHg from baseline or an improvement to > 75 mmHg at 3 hours.
Reference
Khanna A, English SW, Wang XS et al. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med. 2017 Aug 3;377(5):419-430.
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