Intravenous aprepitant for prevention of postoperative nausea and vomiting in adults at moderate-to-high risk in China: a multicenter, randomized, double-blind, placebo-controlled trial

Abstract Purpose To evaluate whether peri-induction intravenous aprepitant 32mg/4.4ml improves the complete response (CR) to postoperative nausea and vomiting (PONV) within 24 h after surgery, as well as the 0–48 h net clinical effect, safety, and pharmacokinetic outcomes, in Chinese adults at moderate to high risk of PONV under a standardized rescue protocol. Methods This multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted in 30 hospitals in China. A total of 412 patients scheduled for abdominal or pelvic surgery with an Apfel simplified risk score ≥ 2 were randomized 1:1 to the aprepitant group ( n = 206) or placebo ( n = 206). Patients in the aprepitant group received intravenous aprepitant 32 mg before anesthesia induction, while those in the control group received placebo. Rescue antiemetics were administered only for clinically significant postoperative symptoms. The primary endpoint was CR within 24 h after surgery, defined as no vomiting or retching and no use of rescue antiemetic therapy during the first 24 postoperative hours. Secondary endpoints included time to first emesis within 48 h, incidence of moderate-to-severe nausea within 24 h, and rescue antiemetic use within 24 h after surgery. A pharmacokinetic substudy ( n = 28) measured plasma aprepitant concentration at 0 and 2 min, 5 min, 15 min, 1 h, 3 h, 6 h, 24 h and 48 h after completion of administration. Adverse events were recorded to assess safety. Results Aprepitant significantly increased the rate of CR within 24 h compared with placebo (81.4% vs. 39.0%; P < 0.001). Vomiting within 48 h occurred less frequently in the aprepitant group than in the control group (16.7% vs. 62.0%; P < 0.001), and time to first emesis within 48 h was significantly delayed with aprepitant (log-rank P < 0.001). The proportion of patients with no emesis was higher in the aprepitant group at both 24 h (84.8% vs. 40.0%; weighted risk difference, 45.07% [95% CI, 36.90%–53.24%]) and 48 h (83.3% vs. 38.0%; weighted risk difference, 45.55% [95% CI, 37.29%–53.81%]). Moderate-to-severe nausea within 24 h was reduced with aprepitant (16.7% vs. 33.2%; P < 0.001), as was rescue antiemetic use within 24 h (8.3% vs. 22.0%; P < 0.001). In the pharmacokinetic substudy, the mean (SD) C max was 4997.95 (1226.44) ng/mL, the median (range) T max was 0.035 (0.031–0.076), and the mean (SD) half-life ( T 1/2 ) was 9.08 (2.17). Adverse reaction profiles were similar between groups. Conclusions Peri-induction intravenous aprepitant 32 mg substantially improved the 24 h CR rate in Chinese adults at moderate to high risk of PONV undergoing abdominal or pelvic surgery. This benefit was accompanied by delayed time to first emesis, reduced moderate-to-severe nausea, and lower rescue antiemetic use, with a safety profile comparable to placebo. Clinical trial registration Chinese Clinical Trial Registry, ChiCTR2400082488. Registered on 29 March 2024, https://www.chictr.org.cn/showproj.html?proj=224587 .