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Safety Study of Hemospan® in Prostatectomy Patients

Primary Purpose

Blood Loss, Surgical, Prostate Cancer, Surgery

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Hemospan (MP4OX)

Ringer's lactate

About this trial

This is an interventional treatment trial for Blood Loss, Surgical focused on measuring Blood loss, Ischemia, Hemoglobin, Blood Substitutes, Plasma Expanders

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

Johns Hopkins Medical Institutions

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Hemospan (MP4OX)

Control

Arm Description

4.3 g/dL MalPEG-Hb solution

Ringer's lactate

Outcomes

Primary Outcome Measures

Incidence of adverse events

Secondary Outcome Measures

Changes in oxygenation, perfusion and cardiovascular status

Number and type of cardiac rhythm disturbances

Number and duration of intraoperative hypotensive episodes

Incidence of pharmacologic interventions for cardiovascular support

Duration of supplemental oxygen use

Volume of intravenous fluid administered

Blood products administered

Full Information

NCT ID

NCT00425334

First Posted

January 18, 2007

Last Updated

August 15, 2013

Sponsor

Sangart

1. Study Identification

Unique Protocol Identification Number

NCT00425334

Brief Title

Safety Study of Hemospan® in Prostatectomy Patients

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2013

Overall Recruitment Status

Completed

Study Start Date

July 2005 (undefined)

Primary Completion Date

October 2007 (Actual)

Study Completion Date

November 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sangart

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Blood Loss, Surgical, Prostate Cancer, Surgery

Keywords

Blood loss, Ischemia, Hemoglobin, Blood Substitutes, Plasma Expanders

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

Participant

Allocation

Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Hemospan (MP4OX)

Arm Type

Experimental

Arm Description

4.3 g/dL MalPEG-Hb solution

Arm Title

Control

Arm Type

Active Comparator

Arm Description

Ringer's lactate

Intervention Type

Drug

Intervention Name(s)

Hemospan (MP4OX)

Other Intervention Name(s)

MP4OX solution, 4.3 g/dL MalPEG Hb, PEGylated Hb

Intervention Description

250 mL or 500 mL Hemospan (MP4OX)

Intervention Type

Drug

Intervention Name(s)

Ringer's lactate

Other Intervention Name(s)

Lactated Ringers, Ringers solution, Hartmann's solution

Intervention Description

250 mL or 500 mL Ringer's lactate USP

Primary Outcome Measure Information:

Title

Incidence of adverse events

Time Frame

One month

Secondary Outcome Measure Information:

Title

Changes in oxygenation, perfusion and cardiovascular status

Time Frame

3 days

Title

Number and type of cardiac rhythm disturbances

Time Frame

3 days

Title

Number and duration of intraoperative hypotensive episodes

Time Frame

6 hours

Title

Incidence of pharmacologic interventions for cardiovascular support

Time Frame

3 days

Title

Duration of supplemental oxygen use

Time Frame

3 days

Title

Volume of intravenous fluid administered

Time Frame

3 days

Title

Blood products administered

Time Frame

3 days

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John Ulatowski, M.D., Ph.D.

Organizational Affiliation

Johns Hopkins University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Peter E. Keipert, Ph.D.

Organizational Affiliation

Sangart, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Johns Hopkins Medical Institutions

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

15820947

Citation

Bjorkholm 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.

Results Reference

background

PubMed Identifier

16096458

Citation

Young 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.

Results Reference

background

PubMed Identifier

16857991

Citation

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. doi: 10.1182/blood-2006-02-005272. Epub 2006 Jul 20.

Results Reference

background

PubMed Identifier

16907870

Citation

Winslow 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.

Results Reference

background

PubMed Identifier

17122578

Citation

Olofsson 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.

Results Reference

background

PubMed Identifier

17198847

Citation

Winslow RM. Red cell substitutes. Semin Hematol. 2007 Jan;44(1):51-9. doi: 10.1053/j.seminhematol.2006.09.013.

Results Reference

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Safety Study of Hemospan® in Prostatectomy Patients

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