| | PI: Richard Wunderink, MD Pager 5-9789 Contact the PI or the Pulmonary Research pager (5-9285) for questions and enrollment | Indications: MICU - Sepsis | IRB Approval # 1444-024 | Inclusion Criteria* | Provision of signed informed consent (by the patient or his/her legally authorised representative) Aged ≥18 years Clinical evidence of infection requiring treatment with parenteral antibiotics as evidenced by 1 of the following: Perforated viscus White blood cells (WBC) and/or pathogens in a normally sterile body fluid Radiographic evidence of pneumonia in association with the production of purulent sputum Signs of a local source of infection such as cellulitis A syndrome associated with a high risk of infection (eg, ascending cholangitis) Positive culture from blood or from another normally sterile body fluid prior to study drug administration
Patients must meet at least 3 of the following 4 SIRS criteria: Core temperature of >38°C or <36°C measured via tympanic, oral, rectal (preferred), or thermistor method Heart rate of >90 beats per minute Respiratory rate (RR) of >20 breaths/minute related to septic event or partial pressure of arterial carbon dioxide (PaCO2) <32 mmHg related to septic event or requiring mechanical ventilation related to septic event Total WBC absolute count >12000 cells/mm3 or <4000 cells/mm3. In the presence of granulocyte stimulating factor all 3 other vital sign criteria must be met
Patients must meet criteria for cardiovascular and/or respiratory dysfunction . Newly developed organ dysfunctions must be in the context of the acute septic process not explained by a chronic condition or by effects of concomitant therapy. Sepsis (infection + SIRS criteria) must be present prior to cardiovascular and/or respiratory dysfunction. SIRS criteria and cardiovascular and/or respiratory dysfunction do not need to be present simultaneously but SIRS criteria must have been met within the 24 hours preceding the initial cardiovascular and/or respiratory dysfunction.
| Exclusion Criteria* | - Clinical judgment by the investigator that the patient should not participate in the study
- Human immunodeficiency virus infection in association with a last known cluster of differentiation (CD)4 count of ≤50/mm3
- Moribund, and death is considered imminent (within 24 hours of recognition of sepsis)
- Patient not expected to survive 90 days because of underlying medical condition such as poorly controlled neoplasm
- Patient cannot attain a mean arterial pressure >60 mmHg when measured via an arterial line and/or a systolic blood pressure (BP) >80 mm Hg in the presence of vasopressors and iv fluids for a period ≥2 hours
- Classified as “Do Not Resuscitate”, or “Do Not Treat”, or the patient’s family is not committed to aggressive management of the patient’s condition. A “no cardiopulmonary resuscitation (CPR)” order is acceptable if the patient and/or the family are still committed to aggressive care short of CPR
- Any organ or bone marrow transplant within the 6 months prior to provision of written informed consent for the study
- Receiving immunosuppressants, for example, methotrexate, cyclosporine, tacrolimus (Protopic®, Fujisawa Healthcare, Inc.), high dose steroids (eg, >40 mg prednisone or a steroid with equivalent activity, daily for >2 weeks) within 2 months before provision of informed consent for the study
- Haemopoietic and lymphoreticular malignancies, unless in remission (patients in remission must have completed induction and consolidation therapy before provision of written informed consent for the study)
- Patients undergoing active radiation or chemotherapy (including non-cytotoxic) treatment for any type of malignancy
- Severe chronic liver disease associated with portal hypertension, cirrhosis, chronic ascites or Child-Pugh class C
- Second or 3rd degree burns involving more than 30% of body surface within 5 days before provision of written informed consent for the study
- Proven myocardial infarction within the last 6 weeks before provision of written informed consent for the study
- Documented history of moderate to severe chronic heart failure as defined by New York Heart Association (III and IV) or an ejection fraction <30%
- Females of child bearing potential who do not have a negative pregnancy test (serum) at screening (patients may be entered into the study on the basis of a negative urine pregnancy test, pending the results of a serum pregnancy test; if the serum pregnancy test is positive, the patient must be discontinued from study treatment)
- Any history of hypersensitivity reaction to sheep products, latex, papain or papaya, chymopapain, eg, meat tenderisers or contact lens cleaning solution containing papain or chymopapain
- Previously administered antivenom manufactured using ovine serum, digoxin immune fab (DigiFab™, DIGIBIND®) crotalidae polyvalent immune fab (ovine) (CroFab™), or other sheep-derived product
- Treatment with anti-TNF antibodies (eg, infliximab [REMICADE®, Centocor], adalimumab [Humira®, Abbot Laboratories], etanercept [Enbrel®, Immunex]) within 8 weeks before provision of written informed consent for the study
- Enrolment in another experimental protocol within 60 days before provision of written informed consent for the study
- Deep-seated fungal infection (eg, cryptococcal meningitis and aspergillosis). Superficial fungal infections are not excluded (eg, tinea pedis, yeast [eg, oral thrush, candida dermatitis] infections limited to skin)
- Active tuberculosis
- Acute pancreatitis
- Severe chronic respiratory disease (ie, present before the onset of the current episode of severe sepsis). Severe disease as defined by any one or more of the following:
Forced expiratory volume in 1 second (FEV1) <20 mL/kg ideal BW (eg, 1.4 L for a 70 kg person), OR FEV1/vital capacity <50% predicted, OR Chronic hypercarbia (PaCO2 >45 mmHg) and /or chronic hypoxemia (partial pressure of arterial oxygen [PaO2] <55 mmHg) on fraction of inspired oxygen (FiO2)=0.21, OR Radiographic x-ray evidence of any chronic over-inflation or chronic interstitial infiltration, OR Hospitalisation for respiratory failure (PaCO2 >50 mmHg or PaO2 <55 mmHg or O2-Sat <88% on FiO2 =0.21) within 6 months before provision of written informed consent for the study, OR Chronic restrictive, obstructive, neuromuscular, chest wall or pulmonary vascular disease resulting in severe exercise restriction, eg, unable to climb stairs or perform household duties, secondary polycythemia, severe pulmonary hypertension (mean peak airway pressure >40 mmHg), or respiratory dependency, OR Use of home oxygen prior to hospital admission 24. Neuromuscular disease that impairs the patient’s ability to ventilate spontaneously (eg, C5 or higher spinal cord injury), cerebral vascular event (stroke), amyotrophic lateral sclerosis, Guillian-Barré syndrome and myasthenia gravis
- Granulocytopenia as evidenced by leucocyte absolute neutrophil count <500 per μL
- Patient not ambulatory prior to onset of sepsis
- Patient required CPR prior to study drug administration
| * This information is provided as a general guildine. Not all Inclusion / Exclusion Criteria are listed. | |
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