Safety Study of Hemospan® in Prostatectomy Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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Donor (allogeneic) blood transfusions are often required during and/or after elective surgery to maintain adequate hemoglobin concentration, prevent tissue ischemia (inadequate perfusion), treat hypotension (low blood pressure), and compensate for fluid shifts. Hemospan is a novel hemoglobin-based oxygen carrier and plasma expander specifically developed to perfuse and oxygenate tissue at risk for ischemia and hypoxia (insufficient oxygenation). As a result of the molecular size and oxygen dissociation characteristics, Hemospan selectively off-loads oxygen in tissues predisposed to low oxygen tension. In preclinical studies Hemospan has been found to be free of significant toxicity in a variety of animal species. These studies have also demonstrated that Hemospan may be ideally suited for this application, and may even perform better than blood in certain situations. Hemospan has been evaluated in three clinical studies, including a 90-patient multi-center Phase II orthopedic surgery trial completed in Sweden in 2005. No serious adverse events attributable to Hemospan have been noted in any of these trials. Sangart is developing Hemospan as an oxygen-carrying plasma expander and hemodiluent for patients undergoing elective surgical procedures. In the current Phase II study in prostatectomy patients, the administration of Hemospan (Treatment) or Ringer's lactate (Controls) occurs after approximately 250 mL of surgical blood loss has occurred. Study evaluations include clinical observations, subjective symptoms, vital signs, ECG, pulmonary hemodynamics (by TEE), serum chemistry, hematology, urinalysis, renal function, and oxygenation measurements, as well as a safety follow-up assessment at 4-6 weeks after surgery. An independent Data Safety Monitoring Board (DSMB) will review the safety data following completion of each dosing cohort.

Official Title
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A Clinical Safety (Phase II) Increasing Dose Study of MP4 (Hemospan®) in Total Prostatectomy Surgical Patients

Conditions
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Blood Loss, Surgical, Prostate Cancer, Surgery

Intervention / Treatment
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* Drug: Hemospan (MP4OX)
* Drug: Ringer's lactate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hemospan (MP4OX)<br>4.3 g/dL MalPEG-Hb solution | Drug: Hemospan (MP4OX)<br>* 250 mL or 500 mL Hemospan (MP4OX)<br>* Other names: PEGylated Hb;|
| Active Comparator: Control<br>Ringer's lactate | Drug: Ringer's lactate<br>* 250 mL or 500 mL Ringer's lactate USP<br>* Other names: Hartmann's solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events |  | One month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in oxygenation, perfusion and cardiovascular status |  | 3 days | 
| Number and type of cardiac rhythm disturbances |  | 3 days | 
| Number and duration of intraoperative hypotensive episodes |  | 6 hours | 
| Incidence of pharmacologic interventions for cardiovascular support |  | 3 days | 
| Duration of supplemental oxygen use |  | 3 days | 
| Volume of intravenous fluid administered |  | 3 days | 
| Blood products administered |  | 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood loss, Ischemia, Hemoglobin, Blood Substitutes, Plasma Expanders