A Dose Escalation and Safety Study of I5NP in Patients Undergoing Major Cardiovascular Surgery

Exclusion Criteria

• •Patient has undergone any organ transplant
• •Patient who has had cancer or may be predisposed to develop cancers such as those with family history of cancers in multiple relatives {i.e., Familial Polyposis Coli, those with family history of Von Hippel Landau disease (associated with renal cell cancers and renal cysts) and those with family history of Li-Fraumeni syndrome (associated with inherited mutations of the p53 tumor-suppressor gene)}
• •Patient has a history of any abnormality on chest X-ray that could represent a malignancy
• •Patient has a clinically significantly elevated pancreatic and/or hepatic enzyme level, defined as any grade 2, 3 or 4 value according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 3.0
• •Patient has an underlying medical condition which increases the risk of perioperative complications, such as poorly controlled diabetes mellitus or hypertension or significant chronic obstructive pulmonary disease (COPD)
• •Women of childbearing potential are to be excluded from this study. Every female subject is considered of childbearing potential unless she has had sterilization surgery, or is post-menopausal.
• •* Women 21-59, post-menopausal is defined as no menses for at least 12 months and an elevated follicle stimulating hormone (FSH) level.
• •* Women 60-85, post-menopausal is defined as no menses in at least 12 months.
• •Patient has participated in a study of an experimental therapy in the last 30 days
• •Patient is currently receiving immunosuppressive therapy \[this criterion does NOT apply to topical steroids and inhalation steroids for chronic obstructive pulmonary disease (COPD) and/or asthma\]
• •Patient requires pre-operative dialysis or is currently on dialysis
• •Patient is undergoing aortic aneurism repair
• •Pre-operative extracorporeal membrane oxygenation
• •Pre-operative tracheotomy, or mechanical ventilation
• •Patient has Intra-Arterial Balloon Pump (IABP) or other Left Ventricular Assist Device (LVAD)
• •Evidence that patient is experiencing possible AKI prior to surgery, defined as a \> 1.5 times increase in serum creatinine from screening to any time prior to surgery
• •Baseline serum creatinine \> 3.0 mg/dL and/or an estimated GFR of \< 30 mL/min/1.73 m2, as calculated by the Modification of Diet in Renal Disease \[MDRD\] Study equation: eGFR (mL/min/1.73 m2) = \[186 x (SCr)\] - \[1.154 x (Age)\] - \[0.203 x (0.742 if female or 1.210 if African-American female)\] where SCr: serum creatinine in mg/dL and age is in years
• •Patient has comfort measures only or do not resuscitate (DNR) status
• •Patient is participating in a concurrent interventional study
• •Patient has received intravenous contrast material \< 48 hours prior to surgery
• •In the opinion of the investigator a pre-operative concomitant disease or clinical finding such as an abnormality in clinical lab results, chest X-ray, EKG, or physical examination finding that significantly raises the risk of perioperative complications precludes dosing of the patient
• •Patient on CBM for \> 3 hours
• •Patient experienced major blood loss (\>15 units)
• •Use of balloon pump or other LVAD during surgery;
• •In the opinion of the investigator, an intra-operative complication precludes dosing of the patient
• •Cardiac Index \< 2.1 L/min/m2 (applies only to patients with a Swan-Ganz or other PA catheter)
• •Patient has a body temperature ≥ 40 °C
• •Use of IABP post-surgery
• •Fluid imbalance in excess of 15 liters
• •PaO2:FiO2 \< 250
• •Patient receiving ≥ 3 concurrent vasopressors to maintain hemodynamic stability
• •In the opinion of the investigator a post-operative complication precludes dosing of the patient