The addition of angiotensin II (Giapreza; La Jolla Pharma) to standard vasopressors has shown to significantly improve survival at Day 28 in patients with severe vasodilatory shock. The results come from the Phase 3 ATHOS-3 study which has been published in Critical Care Medicine.

Giapreza was approved in December 2017 to raise blood pressure in adults with septic or other distributive shock. In ATHOS-3, patients with a high severity of illness (APACHE II [Acute Physiology and Chronic Health Evaluation II] score >30 or baseline MAP <65mmHg) receiving norepinephrine or the equivalent, were randomized to the addition of IV angiotensin II (n=163) or placebo (n=158). The primary endpoint of mean arterial pressure (MAP) increase of ≥10mmHg or a MAP of ≥75mmHg was achieved by 70% in the Giapreza group vs  23% in the placebo group (P<0.001). Both treatment arms received standard-of-care vasopressors

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Moreover, patients with a baseline APACHE II scores >30 had a significantly improved 28-day mortality trend in the angiotensin II group vs the placebo group: 54.2% (n=52) compared to 70.4% (n=50), respectively (hazard ratio 0.66, 95% CI: 0.40, 1.09; P=0.10). In patients with more severe disease at baseline, the 28-day mortality with the angiotensin II and placebo groups was 51.8% (n = 58) and 70.8% (n = 65), respectively (HR 0.62; 95% CI = 0.39- 0.98; P=.037).

The most common adverse events were thrombocytopenia, tachycardia, fungal infection, delirium, acidosis, hyperglycemia and peripheral ischemia; which occurred in ≥4% of the angiotenisin II group vs. ≥1.5% for the placebo group. 

The full results of ATHOS-3 will be presented at the Society of Critical Care Medicine’s annual congress being held in San Antonio, TX.

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