PURPOSE:    

• This study is designed to show that PEN110-treated blood is not less effective than untreated blood. 
• Safety is being evaluated by showing that the number of adverse events experienced by patients transfused with PEN-treated blood is no more than twice that of patients transfused with untreated blood. 
• Other safety issues being studied include evaluating PEN110-specific antibodies or other antibodies that may develop following transfusion, evaluating the number of blood units transfused, and evaluating any transfusion complications and laboratory changes. 
• This study focuses on the safety and transfusion effectiveness of the PEN110.  The effectiveness of the ability of PEN110 to inactivate pathogens (viruses, bacteria, and parasites) was previously tested in laboratory studies.

BACKGROUND:    

• Since 1980, the United States (US) incidence rate of red blood cell (RBC) transfusions has been fairly stable at 45-50 units/1000 population /year.  
• Surgeons have changed their views regarding the need for allogeneic transfusion and today; many surgeons routinely consider the use of alternatives to allogeneic transfusions. The blood supply remains vulnerable to the introduction of emerging infectious diseases as a result of pathogens potentially crossing species barriers or due to endemic pathogens becoming globalized by human travel and commerce.
• Therefore, the development of a safe and effective pathogen inactivation technology for the preparation of RBCs (Red Blood Cells) would represent an important advancement in transfusion medicine.  An ideal solution for pathogen inactivation is a compound capable of broad-spectrum inactivation of pathogens in RBCs without affecting the quality of the RBCs. 
• The Phase 1 clinical study, incorporating a crossover study design, assessed the safety and in vivo survival of a 10 mL aliquot of PEN110-treated, 51Cr-labeled, autologous red cells. Data from 12 study subjects indicated that PEN110-treated red cells were well tolerated. . 
• The Phase 2 clinical study was designed to evaluate the maximum storage time of a unit of PEN110-treated autologous RBCs relative to a control red blood cell unit. The Phase 2 study does support the safety of full units of autologous red cells treated with PEN110 that have been stored for up to 42 days.  The Phase 1 and Phase 2 clinical studies have thus far demonstrated that PEN110-treated RBCs, when administered to human subjects, are safe and well tolerated.

CRITERIA FOR INCLUSION OF SUBJECTS:    

• Male or female.
• Females must post-menopausal, surgically sterile, or have negative serum pregnancy test following hospital admission.
• At least eighteen years of age.
• Scheduled to undergo non-emergent cardiac surgery on cardiopulmonary bypass (CPB). 
• Prior cardiac surgery.
• Based on the patient's presurgical assessment; the patient is anticipated, in the Principal Investigator’s judgment, to receive two or more units of allogeneic RBCs.
• Stable renal, liver, hematologic and pulmonary function.
• The patient meets the criteria of the American Society of Anesthesiologists (ASA) Class I, II, or III.
• The patient understands and has signed the Informed Consent Form (a legal guardian may not sign for the patient).

CRITERIA FOR EXCLUSION OF SUBJECTS: 

• Any patient who has predonated autologous blood, or has been scheduled for acute normovolemic hemodilution (ANH).
• Presence of active hemorrhage preoperatively.
• Not anticipated to require at least two units of allogeneic RBCs.
• History of hepatitis or HIV seropositivity as determined by serologic tests.
• History of hemolytic anemia or idiopathic hematologic abnormality, or currently DAT positive.
• Preoperative administration of recombinant erythropoietin (r-EPO) within the 4-week period prior to the scheduled surgery.
• Inability or unwillingness to abide by the protocol.
• Previous participation in this study or participation in another investigational drug or device study within the previous 30 days.
• Pregnancy and/ or lactation.   During the perioperative period, patients who develop acute life-threatening or significant destabilizing events occurring just prior to first administration of study blood will be withdrawn from the study (e.g., myocardial infarction, arrhythmia, and shock). 

RECRUITMENT OF SUBJECTS:

• Investigator's will recruit patients from St. Paul University Hospital and Parkland Health & Hospital System.

For more information, please contact Nicklett Johnston, RN at 214-645-7728.