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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
  Purpose

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 Intervention Phase
Hypotension
Hypoxia
Drug: Hemospan (MP4OX)
Drug: Ringer's lactate
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Clinical Safety (Phase Ib/II) Increasing Dose Study of MP4 (Hemospan) in Orthopedic Surgery Patients

Resource links provided by NLM:


Further study details as provided by Sangart:

Primary Outcome Measures:
  • Incidence of adverse events [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 30
Study Start Date: April 2003
Study Completion Date: August 2006
Primary Completion Date: July 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00494949

Locations
Sweden
Department of Orthopedics, Karolinska Hospital
Stockholm, Sweden, SE-171 76
Department of Orthopedics, Stockholm Söder Hospital
Stockholm, Sweden, SE-171 76
Sponsors and Collaborators
Sangart
Investigators
Principal Investigator: Christina I. Olofsson, MD, PhD Karolinska University Hospital, Stockholm
  More Information

Additional Information:
Publications:
Responsible Party: Sangart
ClinicalTrials.gov Identifier: NCT00494949     History of Changes
Other Study ID Numbers: 3002
Study First Received: June 28, 2007
Last Updated: August 15, 2013
Health Authority: Sweden: Medical Products Agency

Keywords provided by Sangart:
Anesthesia, spinal
Blood substitutes
Oxygen therapeutics
Orthopedic surgery
Plasma expanders
Vasoconstriction
Hemospan

Additional relevant MeSH terms:
Hypotension
Cardiovascular Diseases
Vascular Diseases
Pharmaceutical Solutions
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014