Clinical Trials
Study 3002 – Phase 1b/2 Orthopedic Surgery (Sweden)
Details
This single-blind, controlled, dose-escalation, safety and tolerability phase 1b/2 study was conducted at the Karolinska and Söder Hospitals in Stockholm, Sweden. A total of 30 orthopedic surgery patients (ages 27 – 76 years old) were given doses ranging from 200 to 1000 mL of either MP4OX or Ringer's acetate, in five cohorts of 6 patients (4 active and 2 control per cohort) just prior to induction of spinal anesthesia. The primary objective was to evaluate the safety of increasing doses of MP4OX. Secondary objectives were to assess possible effectiveness of MP4OX to support oxygenation, perfusion and hemodynamic stability. [Protocol details can be found at http://clinicaltrials.gov/ct/show/NCT00494949].
Summary of Results
The results of this study have been published in Transfusion Medicine.
Olofsson C, Nygårds EB, Ponzer S, Fagrell B, Przybelski R, Keipert PE, Winslow N, Winslow RM: A randomized, single blind, increasing dose safety trial of an oxygen-carrying plasma expander (Hemospan®) administered to orthopedic surgery patients with spinal anesthesia. Transfusion Med, 18: 28-39, 2008.http://www.ncbi.nlm.nih.gov/pubmed?term=18279190]
A summary of the key safety findings is provided below.
Adverse Events: There were no serious adverse events (SAEs) reported in the study. Adverse events (AEs) that were reported were mild to moderate in intensity (mostly nausea and pyrexia), and the AE rate was similar between controls and MP4OX-treated patients; The safety data suggest that MP4OX was well tolerated at doses up to 1000 mL.
Cardiac Findings: No clinically significant changes in ECG parameters or differences between the MP4OX or control groups were seen. Overall, hematology parameters remained stable during the study. Troponin T was transiently elevated in 2 MP4OX patients (400-mL and 1000-mL cohorts); however, neither had CK-MB elevations or ECG abnormalities.
Laboratory Findings: MP4OX administration was associated with transient elevations in liver enzymes (ALT, AST, and GGT). Lipase and amylase increases at single time points occurred in 1 MP4OX and 2 LR control patients. Renal function by iohexol clearance did not reveal any clinically relevant changes or between-group differences, suggesting no adverse effect of MP4OX on glomerular filtration and renal function. Individual increases in urine β2-microglobulin levels were observed for some patients in the 1000-mL and 750-mL cohorts. Increases in urine N-acetyl glucosamine (NAG) levels were also seen in the 1000-mL MP4OX group. Urine NAG levels have been shown to rise when increased protein is presented to the tubular cells; hence, NAG levels may reflect altered function in renal tubules and not simply an indicator of damage. Serum concentrations of anti-pegylated hemoglobin antibodies, measured by immunoassay, showed no treatment related elevations in antibody titer in MP4OX-treated patients.