Phase III Study of Hemospan® to Prevent Hypotension in Hip Arthroplasty

• Proportion of patients who develop at least one hypotensive episode during anesthesia/surgery and throughout the postoperative period (the first 6 hours following skin closure) [ Time Frame: Up to 6 hours after skin closure ] [ Designated as safety issue: No ]
  

• Incidence of serious operative and postoperative complications, combined into a Composite Morbidity Outcome that includes acute heart failure, acute MI, ischemic stroke, and renal failure [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  
• Incidence of operative and postoperative organ dysfunction related to ischemia and/or tissue hypoxia, as a Composite Ischemia Outcome that includes clinical evidence of cerebral ischemia, myocardial ischemia, and renal dysfunction [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  
• Mortality (in-hospital, and all-cause at 30 days) [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  
• Time to the first hypotensive episode (SBP < 90 mmHg or < 75% of BL) following completion of the dosing regimen [ Time Frame: Intraoperative ] [ Designated as safety issue: No ]
  
• Time to administration of the second dose [ Time Frame: Intraoperative ] [ Designated as safety issue: No ]
  
• Proportion of patients that only receive/require one dose and avoid hypotension [ Time Frame: Up to 6 hours after skin closure ] [ Designated as safety issue: No ]
  
• Total duration of all hypotensive episodes [ Time Frame: Up to 6 hours after skin closure ] [ Designated as safety issue: No ]
  
• Duration of the longest period of hypotension recorded [ Time Frame: Up to 6 hours after skin closure ] [ Designated as safety issue: No ]
  
• Incidence of intervention with a pressor agent to treat hypotension [ Time Frame: Up to 6 hours after skin closure ] [ Designated as safety issue: No ]
  
• Incidence of postoperative intervention with a diuretic for volume-overload or inadequate urine output [ Time Frame: Post-operative day 3 ] [ Designated as safety issue: No ]
  

Hemospan is a novel hemoglobin-based oxygen carrier developed to perfuse and oxygenate tissue at risk for ischemia and hypoxia. As a result of its molecular size and oxygen binding characteristics, Hemospan selectively off-loads oxygen in tissues predisposed to low oxygen tension. Preclinical evidence suggests that Hemospan provides rapid and effective plasma expansion and tissue perfusion, and that the properties of Hemospan target oxygen release in the microcirculation.

Spinal anesthesia is the preferred choice for hip arthroplasty procedures in elderly patients, but is associated with a functional hypovolemia due to loss of vascular tone that frequently causes acute hypotensive episodes. Hypotension represents a surrogate marker of hypovolemia that may be further exacerbated by surgical bleeding, which can result in decreased cardiac output, insufficient perfusion and inadequate tissue oxygenation. Ischemia resulting from hypotension can adversely affect vital organ function and may result in complications and postoperative morbidity. As the population ages and more patients become candidates for orthopedic reconstruction or joint replacement surgery, the number of patients at risk is increasing. The ideal IV solution for preventing hypovolemia-associated hypotension and improving hemodynamic stability would be an effective plasma expander that promotes tissue perfusion and delivers oxygen to ischemic or marginally hypoxic tissue.

Preclinical animal studies have shown that Hemospan may be well-suited to this application and may even be better than blood in some situations. Data from Sangart's Phase II orthopedic surgery study (No. 6055), published recently by Olofsson et al. (Anesthesiology 2006; 105(6): 1153-63) support the safety and potential benefit of Hemospan for preventing hypotension in orthopedic surgery patients undergoing hip replacement surgery under spinal anesthesia.