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

Apex Bioscience

Status and phase

Completed

Phase 3

Conditions

Shock

Systemic Inflammatory Response Syndrome

Treatments

Drug: pyridoxalated hemoglobin polyoxyethylene conjugate (PHP)

Study type

Interventional

Funder types

Industry

Identifiers

NCT00021502

APX-PHP 99-004

Details and patient eligibility

About

To determine the safety and effectiveness of pyridoxylated hemoglobin polyoxyethylene conjugate (PHP) administered by continuous intravenous (IV) infusion in systemic inflammatory response syndrome (SIRS) patients with shock. PHP is a human-derived chemically modified hemoglobin preparation. PHP selectively scavenges excess nitric oxide (NO) and does so in a catalytic, concentration-dependent reaction that results in the formation of the non-toxic NO metabolite, nitrate. PHP is postulated to reduce excess, toxic levels of NO while allowing critical beneficial levels of the molecule to persist.

Full description

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.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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.