番茄社区

LAS VEGAS -- The primary endpoint was missed in the so-called APRON trial of aprepitant (Emend), a neurokinin-1 receptor antagonist, for symptoms of gastroparesis but the drug shouldn't be completely discounted, researchers said here.

Compared with placebo, aprepitant did not meet the patient-reported 100-mm visual analog scale (VAS) for nausea (met by 46% of patients on aprepitant versus 40% of the placebo group, 95% CI 0.8-1.7; P=0.43), said , of the Mayo Clinic in Jacksonville, Fla., at the annual meeting.

However, the 126-participant study did find that aprepitant use resulted in a greater decline in mean daily hours of nausea over 4 weeks (-2.5 versus -1.2 hrs; P=0.03), mean 4-week Gastroparesis Cardinal Symptom Index (GCSI) score (-1.3 versus -0.7; P=0.001), and greater improvement in multiple other measures of symptom severity including the patient-reported PAGI-SYM instrument and the Gastrointestinal Symptom Rating Scale (GSRS).

, ACG president and session moderator, agreed that future research on aprepitant as a treatment for gastroparesis is necessary.

"I completely think that there needs to be another trial because there are so few drugs that will positively affect gastroparesis," he told 番茄社区. "It was a great proof of concept but is really something that will need further study."

Aprepitant is currently approved for treating nausea in chemotherapy patients and those coming out of surgery. Researchers (as well as manufacturer Merck) thought it might also be effective in gastroparesis.

The multicenter, double-masked trial randomized 126 patients 1:1 to 125 mg/day of oral aprepitant or placebo. The primary efficacy endpoint was either a 25-mm reduction after 4 weeks in patients' VAS reports or a 4-week VAS average of less than 25 mm.

At baseline, 57% of patients had delayed gastric emptying and the remainder had normal or rapid emptying but with gastroparesis symptoms; 29% of the sample was diabetic.

When asked by an audience member why the trial missed its primary endpoint, Farrugia responded: "We're slaves to the outcomes we chose, [in this case it was] 25-mm change. Now we can argue in retrospect that it was too severe, but that was what we chose."

During the presentation Farrugia called attention to the fact that aprepitant showed significant benefits in gastroparesis measures used more commonly, including overall symptom relief and GCSI scores for nausea, vomiting, postprandial fullness, bloating, and abdominal pain.

Farrugia noted that twice as many patients in the treatment group versus the placebo group experienced at least one adverse effect (32% vs 16%, P=0.10), yet most were mild to moderate and none were serious.

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