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Increasing Dose Safety Study of Hemospan in Orthopedic Surgery Patients

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ClinicalTrials.gov Identifier: NCT00494949
Recruitment Status : Completed
First Posted : July 2, 2007
Last Update Posted : August 19, 2013
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Hypotension Hypoxia Drug: Hemospan (MP4OX) Drug: Ringer's lactate Phase 1 Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: A Clinical Safety (Phase Ib/II) Increasing Dose Study of MP4 (Hemospan) in Orthopedic Surgery Patients
Study Start Date : April 2003
Actual Primary Completion Date : July 2006
Actual Study Completion Date : August 2006

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Hemospan (MP4OX)
4.3 g/dL MalPEG-Hb solution
Drug: Hemospan (MP4OX)
200, 400, 600, 750, or 1000 mL of Hemospan (MP4OX)
Other Names:
  • MP4OX solution
  • 4.3 g/dL MalPEG-Hb
  • PEGylated Hb

Active Comparator: Control
Ringer's lactate
Drug: Ringer's lactate
200, 400, 600, 750, or 1000 mL of Ringer's lactate solution
Other Names:
  • Lactated Ringers
  • Ringers solution
  • Hartmann's solution

Primary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: 21 days ]

Secondary Outcome Measures :
  1. Changes from baseline in pulse oximetry [ Time Frame: 4 days ]
  2. Change in Arterial blood gas and blood lactate levels from baseline [ Time Frame: 4 days ]
  3. Duration of supplemental inspired oxygen [FIO2] [ Time Frame: 4 days ]
  4. Number and duration of intra-operative hypotensive episodes (SBP<90 mmHg or a DBP <50 mmHg) [ Time Frame: 4 days ]
  5. Incidence of pharmacologic intervention for hypotension [ Time Frame: 4 days ]
  6. Volume blood products administered [ Time Frame: 4 days ]
  7. Change from baseline in vital signs [ Time Frame: 4 days ]
  8. Changes in serum chemistry and hematology from baseline [ Time Frame: 4 days ]
  9. Volume of IV fluids given [ Time Frame: 4 days ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00494949

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Department of Orthopedics, Karolinska Hospital
Stockholm, Sweden, SE-171 76
Department of Orthopedics, Stockholm Söder Hospital
Stockholm, Sweden, SE-171 76
Sponsors and Collaborators
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Principal Investigator: Christina I. Olofsson, MD, PhD Karolinska University Hospital, Stockholm
Additional Information:
Publications of Results:
Other Publications:
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Responsible Party: Sangart
ClinicalTrials.gov Identifier: NCT00494949    
Other Study ID Numbers: 3002
First Posted: July 2, 2007    Key Record Dates
Last Update Posted: August 19, 2013
Last Verified: August 2013
Keywords provided by Sangart:
Anesthesia, spinal
Blood substitutes
Oxygen therapeutics
Orthopedic surgery
Plasma expanders
Additional relevant MeSH terms:
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Vascular Diseases
Cardiovascular Diseases
Signs and Symptoms, Respiratory
Pharmaceutical Solutions