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

Shock Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00021502
• Other study ID #: APX-PHP 99-004
• Status: Completed
• Phase: Phase 3
• First received: July 18, 2001
• Last updated: August 13, 2009
• Start date: March 2001
• Est. completion date: May 2004

Study information

• Verified date: August 2009
• Source: Apex Bioscience
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1000
• Est. completion date: May 2004
• Est. primary completion date: August 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Shock
• Syndrome
• Systemic Inflammatory Response Syndrome

Intervention

Drug:
• pyridoxalated hemoglobin polyoxyethylene conjugate (PHP)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Apex Bioscience

References & Publications (1)

Kinasewitz GT, Privalle CT, Imm A, Steingrub JS, Malcynski JT, Balk RA, DeAngelo J. Multicenter, randomized, placebo-controlled study of the nitric oxide scavenger pyridoxalated hemoglobin polyoxyethylene in distributive shock. Crit Care Med. 2008 Jul;36( — View Citation