Add-on oral amisulpride for prevention of chemotherapy-induced nausea and vomiting during highly emetogenic chemotherapy: A randomized double-blind placebo-controlled group sequential trial.

IntroductionGuideline-based prophylaxis prevents most vomiting during highly emetogenic chemotherapy (HEC), but nausea remains incompletely controlled, especially where NK1 receptor antagonists and olanzapine are inaccessible or ineffective. Amisulpride, a dopamine D2/D3 antagonist, may add benefit with less sedation than olanzapine.MethodsAdults receiving cisplatin-based or anthracycline-cyclophosphamide HEC were studied during a single cycle in this randomized, double-blind, placebo-controlled group sequential trial. All received intravenous ondansetron and dexamethasone on day 1 plus oral dexamethasone 8 mg twice daily on days 2-4, with oral amisulpride (25 mg before chemotherapy, then 12.5 mg nightly for 3 days) or placebo. The primary endpoint was the 4-day (0-96 h) no-nausea responder rate; the planned sample size of 94 targeted an 18 percentage-point improvement. Two interim and one final analysis used O'Brien-Fleming efficacy and futility boundaries.ResultsThe trial stopped for futility at the second interim analysis (70 participants; 35 per arm). No-nausea response was 65.7% with amisulpride versus 57.1% with placebo (risk difference 8.6 percentage points; 95% CI -14.2 to 31.3; p = 0.461). Complete response (no emesis or rescue medication) was 80.0% versus 68.6% (p = 0.274). VAS, FLIE, rescue medication use, and adverse-event frequency were similar, apart from more frequent constipation with amisulpride.ConclusionsThe 8.6 percentage-point difference favored amisulpride but fell short of the 18-point practice-changing MCID, in a well-controlled placebo arm. Without an olanzapine- or NK1-containing comparator, the trial cannot position amisulpride against those regimens, nor exclude a smaller benefit worth having where they are inaccessible.