A randomized, double-blind study to evaluate the efficacy and safety of three different doses of palonosetron versus placebo in preventing postoperative nausea and vomiting over a 72-hour period

BACKGROUND: We designed this multicenter, randomized, double-blind study to assess the efficacy and safety of three doses of palonosetron, compared with placebo, on the incidence and severity of postoperative nausea and vomiting (PONV) in inpatients for 72 h after surgery. METHODS: Female patients undergoing either elective gynecological or breast surgery were stratified according to two additional PONV risk factors: nonsmoking status and history of PONV and/or motion sickness. Five hundred forty-four patients with one or both of these risk factors were randomized to receive one of the three doses of IV palonosetron (0.025 mg, 0.050 mg, 0.075 mg) or placebo immediately before induction of anesthesia. The primary efficacy end-point was complete response (CR: no emesis and no use of rescue medications) evaluated at the 0-24 and 24-72 h time intervals after surgery. RESULTS: CR rates for placebo and palonosetron 0.075 mg were 36% and 56% for 0-24 h (P = 0.001), 52% and 70% for 24-72 h (P = 0.002) and 36% and 52% (P = 0.010) for the 0-72 h. postoperative interval. Palonosetron 0.075 mg was associated with less intense nausea (e.g., toward "mild" or "none") versus placebo during the 0-24 h (P < 0.001) time interval and significantly delayed median time to emesis (P = 0.002) and treatment failure (P = 0.004). Although CR rates for both the 0.025 mg and 0.050 mg palonosetron doses were not statistically superior to placebo for the 0-24 h or 24-72 h periods, both lower doses reduced nausea severity during the 0-24 h period (P = 0.040 and P = 0.004). CONCLUSION: A single 0.075-mg IV dose of palonosetron effectively reduced the severity of nausea and delayed the time to emesis and treatment failure in the inpatient surgical setting; lower doses were not as effective.