Single IV Aprepitant Dose Cut Postoperative Vomiting Risk in Chinese Trial

A single dose of intravenous aprepitant given just before anesthesia induction sharply reduced postoperative nausea and vomiting in adults at moderate-to-high risk, according to a phase III randomized, double-blind, placebo-controlled trial conducted across 30 hospitals in China. The trial enrolled 412 patients scheduled for abdominal or pelvic surgery whose Apfel simplified risk score was at least 2, meaning they carried multiple risk factors for postoperative nausea and vomiting. Patients received either intravenous aprepitant 32 mg/4.4 mL or matching placebo within 5 minutes before induction, delivered as a 30-second intravenous bolus.

The primary endpoint was complete response within 24 hours after surgery, defined as no vomiting or retching and no use of rescue antiemetic therapy during the first 24 postoperative hours. Complete response was achieved by 81.4 percent of patients in the aprepitant group compared with 39.0 percent in the placebo group, a difference that was highly statistically significant. The Cochran–Mantel–Haenszel weighted risk difference, stratified by Apfel score, was 42.65 percentage points, with a 95 percent confidence interval of 34.28 to 51.01. The authors calculated a number needed to treat of approximately 3, meaning roughly three patients would need to receive the drug for one additional patient to achieve complete response who would not have done so otherwise.

Secondary outcomes reinforced the primary finding. Vomiting within 48 hours occurred in 16.7 percent of the aprepitant group versus 62.0 percent of the control group. Time to first emesis within 48 hours was significantly delayed with aprepitant, as shown by a log-rank test with P < 0.001. The proportion of patients with no emesis at all was higher with aprepitant at both 24 hours (84.8 percent vs. 40.0 percent; weighted risk difference 45.07 percent, 95 percent CI 36.90 to 53.24) and 48 hours (83.3 percent vs. 38.0 percent; weighted risk difference 45.55 percent, 95 percent CI 37.29 to 53.81). Moderate-to-severe nausea within 24 hours, measured as a visual analog scale score greater than 4, affected 16.7 percent of aprepitant patients versus 33.2 percent of controls. Rescue antiemetic use within 24 hours fell from 22.0 percent in the control group to 8.3 percent in the aprepitant group.

The trial was designed to assess the net clinical effect of prophylaxis under a standardized rescue protocol. Rescue antiemetics were administered only for clinically significant symptoms, such as intolerable nausea or more than one episode of vomiting or retching. Ondansetron and/or dexamethasone were recommended for rescue, while NK1 receptor antagonists were deliberately excluded as rescue agents to avoid mechanistic overlap with the study drug. Background multimodal prophylaxis with dexamethasone or 5-HT3 receptor antagonists was not mandated, because the trial aimed to isolate the intrinsic prophylactic effect of peri-induction aprepitant versus placebo within the same perioperative care pathway.

Eligible patients were aged 18 to 70 years with a body mass index of 18 to 30 kg/m², scheduled for abdominal or pelvic surgery under general anesthesia with anticipated inhalational maintenance of at least 1 hour and planned postoperative hospitalization of at least 48 hours. All had an Apfel score of 2 or higher and American Society of Anesthesiologists physical status I to III. Randomization was 1:1, stratified by Apfel score category (2, 3, or 4), using stratified block randomization generated by an independent statistician. Participants, treating clinicians, anesthesiologists, investigators, outcome assessors, and statisticians remained blinded to treatment assignment until the prespecified analysis was complete. Of 456 individuals screened, 44 did not meet eligibility criteria; 412 were randomized, and 409 (204 aprepitant, 205 control) received treatment and completed the trial after three withdrew consent before dosing.

A pharmacokinetic substudy in 28 participants, with plasma concentrations measured in the 14 aprepitant-arm patients, characterized the drug’s exposure profile. Aprepitant concentrations rose rapidly after intravenous administration, with a median Tmax of 0.035 hours, roughly 2.1 minutes, supporting the pharmacologic plausibility of peri-induction dosing to cover the early postoperative risk window. Mean maximum plasma concentration (Cmax) was 4997.95 ng/mL (SD 1226.44), the mean elimination half-life was 9.08 hours (SD 2.17), and mean clearance was 4012.89 mL. The authors note that no universally established minimum effective concentration exists for aprepitant in postoperative nausea and vomiting prevention, and that the linkage between plasma exposure and clinical benefit in this trial remains inferential.

Safety outcomes were broadly similar between groups. In the aprepitant group, 120 of 204 patients experienced 277 adverse events (58.8 percent), compared with 112 of 205 patients experiencing 263 adverse events (54.6 percent) in the control group. All adverse events were grade 1 to 3. Three serious adverse events occurred overall, one in the aprepitant group (acute pyelonephritis) and two in the control group (bile leak and pelvic infection), all considered possibly unrelated to the study drug. Adverse drug reactions occurred in 26.5 percent of aprepitant patients and 23.9 percent of controls. No grade 4 or 5 adverse events, treatment-related serious adverse events, or clinically meaningful vital sign abnormalities were identified. Two patients in the aprepitant group and none in the control group showed corrected QT interval prolongation of more than 60 ms from baseline, a difference that was not statistically significant, and no patient exceeded a QTc of 500 ms.

Prespecified subgroup analyses showed directionally consistent effects across Apfel risk strata. By Apfel score, complete response with aprepitant versus control was 100 percent versus 76.2 percent for score 2, 78.0 percent versus 35.4 percent for score 3, and 83.0 percent versus 33.3 percent for score 4. Exploratory analyses across BMI category, age group, sex, and Apfel score found no statistically significant treatment-by-subgroup interactions. The authors caution that these analyses were exploratory and hypothesis-generating, that the trial was not powered for confirmatory subgroup comparisons, and that the sex subgroup was limited by few male participants and a 100 percent complete response rate in the male aprepitant subgroup. A center-adjusted sensitivity analysis, adjusting for Apfel score and study center, yielded an adjusted odds ratio of 10.69 (95 percent CI 6.18 to 18.51) for the primary endpoint, with no statistically significant overall effect of study center, supporting robustness of the primary finding.

The trial’s limitations, as described by the authors, include the absence of combination prophylaxis with other antiemetic classes, which limits assessment of potential synergistic effects within multimodal strategies and may affect generalizability. The pharmacokinetic substudy was small and descriptive, not powered to evaluate exposure–response relationships or to determine whether patient-level factors modified exposure or response. The threshold for ‘intolerable nausea’ in the rescue criteria may have varied across patients and centers, though protocol training, prespecified criteria, and standardized documentation were used to reduce this variability. The trial also does not establish superiority of intravenous aprepitant over active antiemetic comparators such as 5-HT3 receptor antagonists or dexamethasone, since the comparison was against placebo under a standardized rescue pathway.

The trial was conducted from April 8, 2024 to July 3, 2024, registered in the Chinese Clinical Trial Registry (ChiCTR2400082488) on 29 March 2024, and reported according to CONSORT guidelines. The study drug was aprepitant injection manufactured by Jiangsu Kanghe Biopharmaceutical Co., Ltd. The authors conclude that peri-induction intravenous aprepitant 32 mg substantially improved the 24-hour complete response rate in Chinese adults at moderate-to-high risk of postoperative nausea and vomiting undergoing abdominal or pelvic surgery, with benefits extending to delayed time to first emesis, reduced moderate-to-severe nausea, lower rescue antiemetic use, and a safety profile comparable to placebo. They position intravenous aprepitant as a component of risk-stratified prophylaxis to be interpreted alongside, rather than as a replacement for, established multimodal antiemetic strategies, and call for future active-comparator and add-on comparative effectiveness trials.

Subject of Research: Intravenous aprepitant for prevention of postoperative nausea and vomiting in adults at moderate-to-high risk

Article Title: 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

Article References: Luo, S., Teng, X., Zhou, Y., Mao, Q., Zhang, Q., Luo, H., Chen, L., Wang, J., Zhou, H., Jing, J., Ye, C., Sun, C., Zhan, R., Ren, J., Chen, C., Qiang, P., Zheng, M., Yu, W., Wang, S., & Duan, K. (2026). 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. Anesthesiology and Perioperative Science, 4(1), Article 37. https://doi.org/10.1007/s44254-026-00184-z

Image Credits: AI Generated

DOI: 10.1007/s44254-026-00184-z

Keywords: aprepitant, postoperative nausea and vomiting, PONV, NK1 receptor antagonist, randomized controlled trial, anesthesia, antiemetic prophylaxis, Apfel score, complete response, pharmacokinetics, abdominal surgery, pelvic surgery