Catecholamine-resistant distributive shock MedDRA version: 9.1 Level: LLT Classification code 10040070 Term: Septic shock
Conditions
Interventions
Product Name: Pyridoxalated hemoglobin polyoxyethylene conjugate
Product Code: PHP
Pharmaceutical Form: Intravenous infusion
CAS Number: 900535-06-0
Current Sponsor code: PHP
Other descriptive name: p
Sponsors
Apex Bioscience, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: SIRS Inclusion Criteria Patients with SIRS as characterized by two or more of the following conditions (worst values in a 24 hour period): a) Either respiratory rate = 20 breaths/minute, or partial pressure of arterial carbon dioxide (PaCO2) = 32 torr, or mechanical ventilation b) Heart rate = 90 beats/minute c) Either hyperthermia = 38°C, or hypothermia = 36°C d) 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 (see guidelines in Section IV.G.) and requiring a norepinephrine dose of =0.3 mcg/kg/min to maintain a MAP = 65 mmHg but = 80 mmHg within the first 36 hours of the initiation of norepinephrine treatment. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion Criteria · Patients who lack documented Informed Consent signed by the patient or his/her legally authorized representative · Patients that are pregnant · Patients less than 18 years old · Patients with suspicion of or active treatment for coronary artery disease within 60 days of enrollment defined as any of the following: Acute myocardial infarction with an abnormal ECG indicative for myocardial infarction or abnormal regional wall motion (echocardiography) Unstable angina with abnormal regional wall motion (echocardiography) and/or EF 6.0 cm demonstrated by echocardiography or MUGA Hospitalization primarily for congestive heart failure NYHA Class IV congestive heart failure · Patients with suspicion of or active treatment for aortic valve heart disease within 60 days of enrollment defined as any of the following: Aortic valve stenosis with area < 1.0 cm2 Severe aortic insufficiency After aortic valve replacement if EF < 35% (If there is no history of coronary artery disease, malignant arrhythmia, congestive heart failure, or aortic valve heart disease, the patient may be enrolled without further cardiac evaluation. If history is ambiguous, an echocardiogram may be performed to exclude suspected diagnosis (e.g. to assess ejection fraction or aortic valve performance). Patients successfully treated for any of the above conditions earlier than 60 days before enrollment, who are asymptomatic and in stable clinical condition, may be enrolled (e.g. CABG 1 year before with no ongoing angina). This rule is not applied in patients with stents. Prior to randomization, the cardiac status of the subject, from the perspective of study eligibility, must be documented in the medical or research record, and be supported by the baseline medical history. · Patients with stage 3 or 4 solid tumors (TMN classification, group staging), hematologic malignancies with high tumor burden, CNS cancer (WHO stage 3 and 4) unless significant tumor mass was removed near occurence of shock. · Patients with dead bowel likely to result in death. After surgical removal of the dead bowel the patient can be enrolled. · Patients receiving/scheduled to receive another investigational drug or have received an investigational drug in the previous 30 days · Patients with known hypersensitivity to blood products · Patients with hypovolemic shock from bleeding or other volume loss . Patients with anaphylactic shock · Patients who are likely to die within days for diseases or conditions other than catecholamine-dependent shock (e.g. multiple organ failure that is irreversible as distinct from multiple organ dysfunction that may resolve) · Patients with Glasgow Coma Score = 7 at the time of admission and prior to the administration of confounding medications such as narcotics, sedative
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: · To compare the effectiveness of continuous infusion PHP plus conventional vasopressor therapy to that of placebo (normal saline) plus conventional vasopressor therapy in patients with catecholamine-resistant distributive shock. Efficacy will be demonstrated by PHP significantly reducing 28-day all-cause mortality. · To compare over 28 days the safety and tolerability of continuous infusion PHP plus conventional vasopressor therapy to the safety and tolerability of placebo plus conventional vasopressor therapy by evaluating mortality, morbidity measured by indicators of organ failure, and the frequency and duration of adverse effects. ;Secondary Objective: -;Primary end point(s): The primary endpoint will be 28 day all-cause mortality | — |
Countries
Austria, Belgium, Germany, Netherlands, Spain, United Kingdom
Outcome results
None listed