Safety Study of Hemospan® in Prostatectomy Patients

This is a progressive dose escalation study designed to evaluate the safety of Hemospan compared to a standard crystalloid solution (Ringer's lactate) in elective surgery patients undergoing total prostatectomy procedures with anticipated blood loss of more than 500 mL. Secondary objectives of this study are to observe possible activity of Hemospan for tissue oxygenation, perfusion and cardiovascular support.

Sex

Male

Minimum age

18 Years

Inclusion Criteria:

* Adult male ASA class I or II patients over the age of 18 scheduled for elective total prostatectomy surgery with anticipated blood loss greater than 500 mL
* Patients must be in good health (other than the indication for prostatectomy surgery) as determined by medical history, physical examination, clinical laboratory studies and electrocardiogram (ECG)
* At screening (within 2 weeks of the scheduled surgery) the blood chemistry and hematology (Hb, Hct, RBC, WBC, platelets, PT, PTT, plasma fibrinogen, fibrin split products and haptoglobin) must be within the laboratory normal limits
* Patients must test negative for HIV and hepatitis screens
* Patients must sign an Informed Consent Form (see Appendix II) for the study, which has been reviewed and approved by the Institutional Review Board, prior to screening and entry into the study
* Patients must be available within the continental United States for the period of this study, and willing to complete the follow-up at 4-6 weeks
* Patients must be able to understand and read English

Exclusion Criteria:

* Any acute or chronic condition which would limit the patient's ability to complete the study or jeopardize the safety of the patient
* History or clinical manifestations of a significant cardiovascular or pulmonary disorder
* Clinically significant psychiatric disorder requiring active treatment
* History of diabetes requiring active treatment
* History or clinical manifestation of significant renal or hepatic disorder
* History of thyroid disease or clinical symptoms consistent with thyroid disease
* History of bleeding disorder
* History or family history of a hemoglobinopathy
* Patients with contraindications to TEE probe insertion
* Patients who have received any other investigational drugs within 30 days prior to administration of the study drug
* Professional or ancillary personnel involved with this study

• BACKGROUNDBjorkholm M, Fagrell B, Przybelski R, Winslow N, Young M, Winslow RM. A phase I single blind clinical trial of a new oxygen transport agent (MP4), human hemoglobin modified with maleimide-activated polyethylene glycol. Haematologica. 2005 Apr;90(4):505-15. PMID 15820947
• BACKGROUNDYoung MA, Riddez L, Kjellstrom BT, Bursell J, Winslow F, Lohman J, Winslow RM. MalPEG-hemoglobin (MP4) improves hemodynamics, acid-base status, and survival after uncontrolled hemorrhage in anesthetized swine. Crit Care Med. 2005 Aug;33(8):1794-804. doi: 10.1097/01.ccm.0000172648.55309.13. PMID 16096458
• BACKGROUNDTsai AG, Cabrales P, Manjula BN, Acharya SA, Winslow RM, Intaglietta M. Dissociation of local nitric oxide concentration and vasoconstriction in the presence of cell-free hemoglobin oxygen carriers. Blood. 2006 Nov 15;108(10):3603-10. doi: 10.1182/blood-2006-02-005272. Epub 2006 Jul 20. PMID 16857991
• BACKGROUNDWinslow RM. Current status of oxygen carriers ('blood substitutes'): 2006. Vox Sang. 2006 Aug;91(2):102-10. doi: 10.1111/j.1423-0410.2006.00789.x. PMID 16907870
• BACKGROUNDOlofsson C, Ahl T, Johansson T, Larsson S, Nellgard P, Ponzer S, Fagrell B, Przybelski R, Keipert P, Winslow N, Winslow RM. A multicenter clinical study of the safety and activity of maleimide-polyethylene glycol-modified Hemoglobin (Hemospan) in patients undergoing major orthopedic surgery. Anesthesiology. 2006 Dec;105(6):1153-63. doi: 10.1097/00000542-200612000-00015. PMID 17122578
• BACKGROUNDWinslow RM. Red cell substitutes. Semin Hematol. 2007 Jan;44(1):51-9. doi: 10.1053/j.seminhematol.2006.09.013. PMID 17198847