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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase 3, Multi-Center, Randomized, Placebo Controlled Study of PHP When Administered by Continuous Infusion in Patients With Shock Associated With Systemic Inflammatory Response Syndrome (SIRS)

Conditions
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Shock, Systemic Inflammatory Response Syndrome

Intervention / Treatment
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* Drug: pyridoxalated hemoglobin polyoxyethylene conjugate (PHP)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: pyridoxalated hemoglobin polyoxyethylene conjugate (PHP)|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pyridoxalated hemoglobin polyoxyethylene conjugate (PHP), Systemic Inflammatory Response Syndrome (SIRS), Nitric oxide (NO), Shock