Clinical Trials

Study 6084 – Phase III Orthopedic Surgery (Europe)

Details
This multicenter, international, double-blind controlled Phase III study (Prevention Trial) was conducted in six countries in Europe. The primary objective was to evaluate the ability of MP4OX to prevent acute hypotension in orthopedic surgery patients undergoing first-time hip replacement procedures under spinal anesthesia. The efficacy endpoints were achieved, demonstrating superiority of MP4OX over Voluven (6% hydroxyethyl starch [HES 130/0.4] solution) for preventing hypotensive episodes during the operative and early postoperative period. The secondary objective was to determine whether MP4OX is superior to Voluven for reducing the incidence of operative and postoperative morbidity (based on composite outcomes for organ dysfunction and failure) associated with ischemia and/or tissue hypoxia, until follow-up at 1 month following surgery (postoperative day [POD] 30 ± 5 days). Adult female (surgically sterile or post-menopausal) or male patients, ≥ 50 years of age, who were scheduled to undergo elective primary hip arthroplasty (based on osteoarthritis diagnosis) with spinal anesthesia and who were classified with American Society of Anesthesiology Class II or III were eligible for enrollment. A total of 394 patients consented to participate, and 376 patients (ages 50 – 86 years old) were randomized at 18 centers from February 2007 to May 2008 and were analyzed for safety (intent to treat [ITT] population). A total of 367 patients received at least a partial dose of investigational product (modified intent to treat [MITT] population) and were analyzed for efficacy. Patients were screened within 2 weeks prior to the day of primary hip arthroplasty surgery and baseline measurements were taken within 1 hour prior to insertion of the spinal needle. To help prevent patients from reaching the hypotension threshold, defined as a systolic blood pressure (SBP) < 90 mm Hg or below 75% of baseline level, the first 250-mL dose was administered at the time of spinal anesthesia induction. The second dose was administered only if the patient reached the protocol-defined trigger (i.e., a SBP < 100 mm Hg or below 80% of the baseline level, whichever is greater) at any time before the end of surgery (skin closure). After surgery, vasopressors, colloids or red blood cell transfusion were administered according to the site’s standard practice, when clinically indicated. [Additional details about the protocol can be found at http://clinicaltrials.gov/ct/show/NCT00421200?order=2]

Results
The results of this study have been submitted for publication (Olofsson et al., European Journal of Anaesthesiology). A detailed summary of the efficacy and safety findings will be provided in the future following publication of these study results.

Summary findings: Overall, MP4OX was superior compared to Voluven for the prevention of hypotension during anesthesia/surgery and throughout the postoperative period (defined as the first 6 hours following skin closure). With respect to the primary endpoint, the proportion of patients who developed at least 1 hypotensive episode during anesthesia/surgery and throughout the postoperative period was significantly lower in the MP4OX group than the Voluven group.

No major clinically important safety concerns were identified and there were no statistically significant imbalances in the incidence of serious adverse events. Overall, clinical chemistry and laboratory findings were not unexpected and were consistent with data from previous clinical studies with MP4OX in surgical patients. The secondary study objective to show that MP4OX treatment would also reduce the incidence of operative and postoperative morbidity and thereby demonstrate clinical benefit in these low-to-moderate risk surgical patients was not achieved.