Increasing Dose Safety Study of Hemospan in Orthopedic Surgery Patients
|Hypotension Hypoxia||Drug: Hemospan (MP4OX) Drug: Ringer's lactate||Phase 1 Phase 2|
|Study Design:||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|
- Incidence of adverse events [ Time Frame: 21 days ]
- Changes from baseline in pulse oximetry [ Time Frame: 4 days ]
- Change in Arterial blood gas and blood lactate levels from baseline [ Time Frame: 4 days ]
- Duration of supplemental inspired oxygen [FIO2] [ Time Frame: 4 days ]
- Number and duration of intra-operative hypotensive episodes (SBP<90 mmHg or a DBP <50 mmHg) [ Time Frame: 4 days ]
- Incidence of pharmacologic intervention for hypotension [ Time Frame: 4 days ]
- Volume blood products administered [ Time Frame: 4 days ]
- Change from baseline in vital signs [ Time Frame: 4 days ]
- Changes in serum chemistry and hematology from baseline [ Time Frame: 4 days ]
- Volume of IV fluids given [ Time Frame: 4 days ]
|Study Start Date:||April 2003|
|Study Completion Date:||August 2006|
|Primary Completion Date:||July 2006 (Final data collection date for primary outcome measure)|
Experimental: Hemospan (MP4OX)
4.3 g/dL MalPEG-Hb solution
Drug: Hemospan (MP4OX)
200, 400, 600, 750, or 1000 mL of Hemospan (MP4OX)
Active Comparator: Control
Drug: Ringer's lactate
200, 400, 600, 750, or 1000 mL of Ringer's lactate solution
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).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00494949
|Department of Orthopedics, Karolinska Hospital|
|Stockholm, Sweden, SE-171 76|
|Department of Orthopedics, Stockholm Söder Hospital|
|Stockholm, Sweden, SE-171 76|
|Principal Investigator:||Christina I. Olofsson, MD, PhD||Karolinska University Hospital, Stockholm|