Clinical Trials

Study 6090 – Phase III Orthopedic Surgery (Europe)

Details
This multicenter, international, double-blind controlled Phase III study (Treatment Trial) was conducted in five countries in Europe. The primary objective was to evaluate the ability of MP4OX to treat 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 treating acute 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 488 patients consented to participate, and 474 patients (ages 50 – 87 years old) were randomized at 21 centers from April 2007 to April 2008 and were analyzed for safety (Intent-to-Treat [ITT] population). A total of 405 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. Patients were randomized in a 1:1 ratio to receive up to two 250-mL units of either MP4OX or Voluven during surgery. The first 250-mL dose was given when patients reached the protocol-defined hypotension threshold (i.e., SBP < 90 mm Hg or below 75% of baseline level, whichever value was higher). The second 250-mL dose was administered only if the patient reached the same protocol-defined hypotension threshold level 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 clinical practice when clinically indicated. [Additional details about this protocol can be found at http://clinicaltrials.gov/ct/show/NCT00420277?order=3]

Results

The results of this study have been submitted for publication (Van der Linden et al., Anesthesiology & Analgesia). 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 treatment of acute hypotensive episodes during anesthesia/surgery and throughout the postoperative period (defined as the first 6 hours following skin closure). With respect to the primary endpoint, the total duration of hypotensive episodes during surgery and throughout the postoperative period was significantly shorter in the MP4OX group compared to 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.