Clinical trial NCT00021502: Safety and Efficacy of PHP in the Treatment of Shock Associated With Systemic Inflammatory Response Syndrome (SIRS)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Shock
Systemic Inflammatory Response Syndrome
Keywords: Pyridoxalated hemoglobin polyoxyethylene conjugate (PHP)
Systemic Inflammatory Response Syndrome (SIRS)
Nitric oxide (NO)
Shock
Lead sponsor: Apex Bioscience
Sponsor class: INDUSTRY
First posted: 2001-07-20
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
citation: 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(7):1999-2007. doi: 10.1097/CCM.0b013e31817bfe84.