Safety and Efficacy of PHP in the Treatment of Shock Associated With Systemic Inflammatory Response Syndrome (SIRS)

This Phase 3, randomized, placebo controlled, multi-center study is designed to evaluate the safety and efficacy of continuous IV infusion of PHP plus conventional vasopressor treatment, as compared to continuous IV infusion of Plasma-Lyte A plus conventional vasopressor, as a treatment for restoring hemodynamic stability in SIRS patients with shock. Conventional vasopressors include dopamine > 5 mcg/kg/min; or norepinephrine, phenylephrine or epinephrine at any dose.

The study consists of a Screening period, a Pre-Treatment period, and a 28-day Treatment period. Efficacy will be determined by evaluating objective clinical measures of mortality and organ function over the 28-day treatment period.

The safety and tolerability of PHP will be evaluated over the continuous 28 days using a number of measures including an evaluation of:

• all cause mortality,
• median patient survival time and
• adverse event rates and duration.

Determination of study eligibility will be made by the Investigator on the basis of the inclusion criteria listed below:

SIRS Inclusion Criteria

Patients with SIRS as characterized by two or more of the following conditions (worst values in a 24 hour period):

• Either respiratory rate >/= 20 breaths/minute, partial pressure of arterial carbon dioxide (PaCO2) </= 32 torr, or mechanical ventilation,
• Heart rate >/= 90 beats/minute,
• Either hyperthermia >/= 38 degrees C, or hypothermia </= 36 degrees C or
• Either white blood cell (WBC) >/= 12,000 cells/mm3, </= 4,000 cells/mm3, or >/= 10% immature (band) forms

Shock Inclusion Criteria Patients with adequate fluid resuscitation (PCWP >/= 12mmHg) and with one or more conventional vasopressors (continuing up to the time of randomization) being used to treat hypotension (MBP < 60 mmHg or SBP < 90 mmHg). Patients cannot be entered if they have been in shock for more than 24 hours.