VBI-S for the Treatment of Hypotension in Septic Shock

Author(s):
Manasa Gadiraju; Nargiz Agayeva; Prashanth Anamthathmakula; Michael Moncure; Heather Klepacz; Sadia Benzaquen; Luis Diaz; Kristopher Roach; Daniel Haase; Juan Rodriguez; Cuthbert Simpkins

Background:

Septic shock leads to 11 million deaths per year worldwide, generating a need for more efficacious treatment options. A major challenge to treatment is a decrease in blood pressure that eventually becomes unresponsive to fluids and vasopressors. This problem is largely mediated by an overproduction of nitric oxide (NO). VBI-S is a patented fluid designed for the pathophysiology of septic shock. It consists of hydrophobic phospholipid nanoparticles that reversibly absorbs NO, a lipophilic molecule. VBI-S may reduce the bioavailability of NO, elevate blood pressure even when fluids and vasopressors are ineffective and redistribute NO without inhibiting its production and homeostatic interactions. The primary aim of this study is to test the safety and efficacy of intravenous infusion of VBI-S in elevating blood pressure in septic shock patients.

Hypothesis:

We hypothesized that intravenous infusion of VBI-S in patients with severe septic shock will increase blood pressure by at least 10 mmHg. We further hypothesized a decrease in the dose of vasopressors required to maintain a mean arterial pressure (MAP) of 60-65 mmHg after VBI-S infusion.

Methods:

The enrollment goal of this open-label phase IIa is twenty patients aged 18 years and above. Hypotensive septic patients in whom fluids have failed to elevate their MAP to 65 mmHg are given up to 1500 ml/24 hours of the test fluid which is VBI-S. Data are mean ± SE.

Results:

Fourteen patients have been enrolled so far. The mean SOFA score of the patients was 15, indicating severe sepsis. After VBI-S infusion, MAP increased from 64.29 ± 1.17 to 76.86 ± 1.22 mmHg (p<0.0001).  The volume of VBI-S needed to achieve the goal was 584.86 ± 103.86 mL. The average dose of vasopressors decreased from 42.65 ± 17.82 to 22.38 ± 13.43 ug/min post-infusion (p=0.032). The time required to maximally reduce vasopressors was 15.50 ± 3.55 hours. Variable doses of VBI-S maintained the blood pressure for 32.04 ± 4.90 hours. Six patients were taken completely off Levophed within 48 hours. These patients had a mean dose of vasopressor as Levophed equivalents of 11.93 ± 2.99 ug/min. Those whose vasopressor dose was reduced to greater than zero had a pre VBI-S vasopressor dose of 87.02 ± 35.00 ug/min and a post VBI-S vasopressor dose of 45.64 ± 29.58 ug/min (p=0.018).

Conclusions:

Intravenous infusion of VBI-S in severely septic patients improved MAP after other fluids had failed and decreased reliance on vasopressors post-VBI-S infusion. No adverse effects of VBI-S were observed. These preliminary data support our hypotheses and suggest the efficacy of VBI-S as a potential treatment for the hypotension caused by the absolute and/or relative hypovolemia of septic shock. Further study is indicated regarding the effect of VBI-S in other organ systems.