Increasing Dose Safety Study of Hemospan in Orthopedic Surgery Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sangart
ClinicalTrials.gov Identifier:
NCT00494949
First received: June 28, 2007
Last updated: August 15, 2013
Last verified: August 2013

June 28, 2007
August 15, 2013
April 2003
July 2006   (final data collection date for primary outcome measure)
Incidence of adverse events [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
  • Fluid intake/output
  • AE occurrence, severity and relationship to study material
  • Vital sign changes (pulse, blood pressure and respiratory rate)
  • Laboratory abnormalities related to organ dysfunction or indicative of toxicity (clinical chemistry, hematology, urinalysis and electrocardiogram [ECG])
  • Blood loss (estimated) during and following surgery
Complete list of historical versions of study NCT00494949 on ClinicalTrials.gov Archive Site
  • Changes from baseline in pulse oximetry [ Time Frame: 4 days ] [ Designated as safety issue: No ]
  • Change in Arterial blood gas and blood lactate levels from baseline [ Time Frame: 4 days ] [ Designated as safety issue: No ]
  • Duration of supplemental inspired oxygen [FIO2] [ Time Frame: 4 days ] [ Designated as safety issue: No ]
  • Number and duration of intra-operative hypotensive episodes (SBP<90 mmHg or a DBP <50 mmHg) [ Time Frame: 4 days ] [ Designated as safety issue: No ]
  • Incidence of pharmacologic intervention for hypotension [ Time Frame: 4 days ] [ Designated as safety issue: No ]
  • Volume blood products administered [ Time Frame: 4 days ] [ Designated as safety issue: No ]
  • Change from baseline in vital signs [ Time Frame: 4 days ] [ Designated as safety issue: No ]
  • Changes in serum chemistry and hematology from baseline [ Time Frame: 4 days ] [ Designated as safety issue: No ]
  • Volume of IV fluids given [ Time Frame: 4 days ] [ Designated as safety issue: No ]
  • The effectiveness of Hemospan for tissue oxygenation and cardiovascular support was assessed with the following parameters: Pulse oximetry measured as per vital signs
  • Arterial blood gas and blood lactates
  • Post-operative oxygen (fraction of inspired oxygen [FIO2] duration in hours)
  • Number and duration of intra-operative hypotensive episodes (defined as a systolic pressure <90 mmHg or a diastolic pressure <50 mmHg)
  • Number and amount of pharmacologic interventions (mL and number of units of packed red blood cells)
  • Amount and type of intravenous fluids administered before, during and after surgery
  • Amount of blood or blood products administered before, during and after surgery
Not Provided
Not Provided
 
Increasing Dose Safety Study of Hemospan in Orthopedic Surgery Patients
A Clinical Safety (Phase Ib/II) Increasing Dose Study of MP4 (Hemospan) in Orthopedic Surgery Patients

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.

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).

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
  • Hypotension
  • Hypoxia
  • 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
  • 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
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
August 2006
July 2006   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Sweden
 
NCT00494949
3002
Yes
Sangart
Sangart
Not Provided
Principal Investigator: Christina I. Olofsson, MD, PhD Karolinska University Hospital, Stockholm
Sangart
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP