Safety Study of Hemospan® in Prostatectomy Patients

Tracking Information
First Submitted Date ICMJE	January 18, 2007
First Posted Date ICMJE	January 22, 2007
Last Update Posted Date	August 19, 2013
Study Start Date ICMJE	July 2005
Actual Primary Completion Date	October 2007 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: August 31, 2011)	Incidence of adverse events [ Time Frame: One month ]
Original Primary Outcome Measures ICMJE; (submitted: January 18, 2007)	To evaluate the safety of Hemospan infusion.
Change History	Complete list of historical versions of study NCT00425334 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: August 31, 2011)	Changes in oxygenation, perfusion and cardiovascular status [ Time Frame: 3 days ]; Number and type of cardiac rhythm disturbances [ Time Frame: 3 days ]; Number and duration of intraoperative hypotensive episodes [ Time Frame: 6 hours ]; Incidence of pharmacologic interventions for cardiovascular support [ Time Frame: 3 days ]; Duration of supplemental oxygen use [ Time Frame: 3 days ]; Volume of intravenous fluid administered [ Time Frame: 3 days ]; Blood products administered [ Time Frame: 3 days ]
Original Secondary Outcome Measures ICMJE; (submitted: January 18, 2007)	To observe possible activity of Hemospan for tissue oxygenation, perfusion and cardiovascular support; Number and type of cardiac rhythm disturbances; Number and duration of intraoperative hypotensive episodes; Pharmacologic interventions for cardiovascular support; Duration of supplemental oxygen use; Amount of intravenous fluid administered; Blood products administered
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Safety Study of Hemospan® in Prostatectomy Patients
Official Title ICMJE	A Clinical Safety (Phase II) Increasing Dose Study of MP4 (Hemospan®) in Total Prostatectomy Surgical Patients
Brief Summary	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	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.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Single (Participant); Primary Purpose: Treatment
Condition ICMJE	Blood Loss, Surgical; Prostate Cancer; Surgery
Intervention ICMJE	Drug: Hemospan (MP4OX) 250 mL or 500 mL Hemospan (MP4OX) Other Names: MP4OX solution 4.3 g/dL MalPEG Hb PEGylated Hb; Drug: Ringer's lactate 250 mL or 500 mL Ringer's lactate USP Other Names: Lactated Ringers Ringers solution Hartmann's solution
Study Arms	Experimental: Hemospan (MP4OX) 4.3 g/dL MalPEG-Hb solution Intervention: Drug: Hemospan (MP4OX); Active Comparator: Control Ringer's lactate Intervention: Drug: Ringer's lactate
Publications *	Björkholm 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.; Young MA, Riddez L, Kjellström 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.; Tsai 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. Epub 2006 Jul 20.; Winslow RM. Current status of oxygen carriers ('blood substitutes'): 2006. Vox Sang. 2006 Aug;91(2):102-10. Review.; Olofsson C, Ahl T, Johansson T, Larsson S, Nellgård 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.; Winslow RM. Red cell substitutes. Semin Hematol. 2007 Jan;44(1):51-9. Review.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: October 4, 2007)	20
Original Enrollment ICMJE; (submitted: January 18, 2007)	40
Actual Study Completion Date	November 2007
Actual Primary Completion Date	October 2007 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: Male
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00425334
Other Study ID Numbers ICMJE	6012
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Sangart
Study Sponsor ICMJE	Sangart
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: John Ulatowski, M.D., Ph.D. Johns Hopkins University Study Director: Peter E. Keipert, Ph.D. Sangart, Inc.
PRS Account	Sangart
Verification Date	August 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP