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Increasing Dose Safety Study of Hemospan in Orthopedic Surgery Patients

Primary Purpose

Hypotension, Hypoxia

Status

Completed

Phase

Phase 1

Locations

Sweden

Study Type

Interventional

Intervention

Hemospan (MP4OX)

Ringer's lactate

About this trial

This is an interventional treatment trial for Hypotension focused on measuring Anesthesia, spinal, Blood substitutes, Oxygen therapeutics, Orthopedic surgery, Plasma expanders, Vasoconstriction, Hemospan

Eligibility Criteria

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

Inclusion Criteria:

Adult male or postmenopausal female(last menses at least 12 months prior and laboratory assessment verifying appropriate FSH and LH levels [laboratory assessments not necessary if last menses at least 12 months prior]), American Society of Anesthesiologists classification system (ASA) class I or II patients over the age of 18 scheduled for orthopedic surgery with spinal anesthesia
Patients have to be in good health (other than the orthopedic indication for surgery) as determined by medical history, physical examination, clinical laboratory studies and ECG, all within four weeks prior to drug administration
At screening (within four weeks prior to drug administration) the iohexol clearance, urinalysis and hematology (hemoglobin, hematocrit, RBC, WBC, platelets, reticulocytes percentage), PT, PTT had to be within the laboratory normal limits, If a clinical laboratory value (Na, K, albumin, serum creatinine, urea, bilirubin, AST, ALT, ALP, GGT, LDH, conjugated bilirubin, lipase, amylase, total protein, C1, Ca, CK, CK-MB, troponin, cholesterol, glucose, β-2 microglobulin, NAG, osmolarity) is outside the normal range the laboratory test can be repeated. A patient with two consecutive abnormal values is not allowed to participate in the study unless the PI determines the change is not clinically significant. A notation of "Not clinically significant (NCS)" is noted on the laboratory record in that case.
Patients have to sign an informed consent form for the study, which is reviewed and approved by the IECs of the Karolinska Hospital or the Stockholm Söder Hospital

Exclusion Criteria:

Any acute or chronic condition which limits the patient's ability to complete the study or jeopardizes the safety of the patient
Patients with a history, or clinical manifestation of significant metabolic disorders, cardiovascular disorders (including arrhythmia, tachycardia, hypertension, angina pectoris, chronic heart failure) or psychiatric disorders
Patients with a history of chronic hepatic or renal disease
Pregnancy
Patients who have received any other investigational drugs within 30 days prior to administration of the study drug
Patients who test positive to human immunodeficiency virus (HIV), hepatitis B or hepatitis C screens or have any other chronic infection
Professional or ancillary personnel involved with the study
Presence of a hemoglobinopathy
Known allergy to iodine-containing intravenous contrast material or seafood
Coagulopathy

Sites / Locations

Department of Orthopedics, Karolinska Hospital
Department of Orthopedics, Stockholm Söder Hospital

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 from baseline in pulse oximetry

Change in Arterial blood gas and blood lactate levels from baseline

Duration of supplemental inspired oxygen [FIO2]

Number and duration of intra-operative hypotensive episodes (SBP<90 mmHg or a DBP <50 mmHg)

Incidence of pharmacologic intervention for hypotension

Volume blood products administered

Change from baseline in vital signs

Changes in serum chemistry and hematology from baseline

Volume of IV fluids given

Full Information

NCT ID

NCT00494949

First Posted

June 28, 2007

Last Updated

August 15, 2013

Sponsor

Sangart

1. Study Identification

Unique Protocol Identification Number

NCT00494949

Brief Title

Increasing Dose Safety Study of Hemospan in Orthopedic Surgery Patients

Official Title

A Clinical Safety (Phase Ib/II) Increasing Dose Study of MP4 (Hemospan) in Orthopedic Surgery Patients

Study Type

Interventional

2. Study Status

Record Verification Date

August 2013

Overall Recruitment Status

Completed

Study Start Date

April 2003 (undefined)

Primary Completion Date

July 2006 (Actual)

Study Completion Date

August 2006 (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

The purpose of this study is to evaluate the safety and possible effectiveness of Hemospan solution in patients undergoing elective orthopedic surgery who receive spinal anesthesia.

Detailed Description

Allogeneic (donor) blood transfusions are often required during and/or after orthopedic hip surgery to maintain adequate hemoglobin concentration, prevent tissue ischemia, treat hypotension, and compensate for fluid shifts. For example, during hospitalization for hip replacement, patients may receive up to two to three units of blood. This amount varies depending on the technical difficulty of the surgery, the patient's hemoglobin concentration prior to surgery, and the patient's clinical status. The limited availability, logistic constraints and documented risks associated with allogeneic blood transfusions have prompted the search for alternative therapies. Autologous (self-donated) red blood cell pre-donation can be used in many cases but age, anemia and co-morbidities often preclude the use of this treatment. Cell saving and re-infusion also prevents blood transfusion, but this practice also has potential problems and limited applicability. Over the past 75 years various "blood substitutes" have been developed for potential clinical use. To date all have shown significant toxicity in preclinical or clinical studies and regulatory approval of these synthetic or hemoglobin-based products has been impeded by safety concerns. Hemospan is a novel polyethylene-modified hemoglobin solution specifically developed to perfuse and oxygenate tissue at risk for ischemia and hypoxia. 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 in doses exceeding those that will be used in this study. In the Phase I safety study in normal volunteers, Hemospan was well tolerated in doses up to 100 mg/kg (approximately 200 mL of a 4g/dL Hemospan solution).

6. Conditions and Keywords

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

Hypotension, Hypoxia

Keywords

Anesthesia, spinal, Blood substitutes, Oxygen therapeutics, Orthopedic surgery, Plasma expanders, Vasoconstriction, Hemospan

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

30 (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

200, 400, 600, 750, or 1000 mL of Hemospan (MP4OX)

Intervention Type

Drug

Intervention Name(s)

Ringer's lactate

Other Intervention Name(s)

Lactated Ringers, Ringers solution, Hartmann's solution

Intervention Description

200, 400, 600, 750, or 1000 mL of Ringer's lactate solution

Primary Outcome Measure Information:

Title

Incidence of adverse events

Time Frame

21 days

Secondary Outcome Measure Information:

Title

Changes from baseline in pulse oximetry

Time Frame

4 days

Title

Change in Arterial blood gas and blood lactate levels from baseline

Time Frame

4 days

Title

Duration of supplemental inspired oxygen [FIO2]

Time Frame

4 days

Title

Number and duration of intra-operative hypotensive episodes (SBP<90 mmHg or a DBP <50 mmHg)

Time Frame

4 days

Title

Incidence of pharmacologic intervention for hypotension

Time Frame

4 days

Title

Volume blood products administered

Time Frame

4 days

Title

Change from baseline in vital signs

Time Frame

4 days

Title

Changes in serum chemistry and hematology from baseline

Time Frame

4 days

Title

Volume of IV fluids given

Time Frame

4 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Adult male or postmenopausal female(last menses at least 12 months prior and laboratory assessment verifying appropriate FSH and LH levels [laboratory assessments not necessary if last menses at least 12 months prior]), American Society of Anesthesiologists classification system (ASA) class I or II patients over the age of 18 scheduled for orthopedic surgery with spinal anesthesia Patients have to be in good health (other than the orthopedic indication for surgery) as determined by medical history, physical examination, clinical laboratory studies and ECG, all within four weeks prior to drug administration At screening (within four weeks prior to drug administration) the iohexol clearance, urinalysis and hematology (hemoglobin, hematocrit, RBC, WBC, platelets, reticulocytes percentage), PT, PTT had to be within the laboratory normal limits, If a clinical laboratory value (Na, K, albumin, serum creatinine, urea, bilirubin, AST, ALT, ALP, GGT, LDH, conjugated bilirubin, lipase, amylase, total protein, C1, Ca, CK, CK-MB, troponin, cholesterol, glucose, β-2 microglobulin, NAG, osmolarity) is outside the normal range the laboratory test can be repeated. A patient with two consecutive abnormal values is not allowed to participate in the study unless the PI determines the change is not clinically significant. A notation of "Not clinically significant (NCS)" is noted on the laboratory record in that case. Patients have to sign an informed consent form for the study, which is reviewed and approved by the IECs of the Karolinska Hospital or the Stockholm Söder Hospital Exclusion Criteria: Any acute or chronic condition which limits the patient's ability to complete the study or jeopardizes the safety of the patient Patients with a history, or clinical manifestation of significant metabolic disorders, cardiovascular disorders (including arrhythmia, tachycardia, hypertension, angina pectoris, chronic heart failure) or psychiatric disorders Patients with a history of chronic hepatic or renal disease Pregnancy Patients who have received any other investigational drugs within 30 days prior to administration of the study drug Patients who test positive to human immunodeficiency virus (HIV), hepatitis B or hepatitis C screens or have any other chronic infection Professional or ancillary personnel involved with the study Presence of a hemoglobinopathy Known allergy to iodine-containing intravenous contrast material or seafood Coagulopathy

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Christina I. Olofsson, MD, PhD

Organizational Affiliation

Karolinska University Hospital, Stockholm

Official's Role

Principal Investigator

Facility Information:

Facility Name

Department of Orthopedics, Karolinska Hospital

City

Stockholm

ZIP/Postal Code

SE-171 76

Country

Sweden

Facility Name

Department of Orthopedics, Stockholm Söder Hospital

City

Stockholm

ZIP/Postal Code

SE-171 76

Country

Sweden

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

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

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

result

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Increasing Dose Safety Study of Hemospan in Orthopedic Surgery Patients

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