1. Aprepitant has Mixed Effects on Nausea and Reduces Other Symptoms in Patients With Gastroparesis and Related Disorders
- Author
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Pankaj J. Pasricha, Katherine P. Yates, Irene Sarosiek, Richard W. McCallum, Thomas L. Abell, Kenneth L. Koch, Linda Anh B. Nguyen, William J. Snape, William L. Hasler, John O. Clarke, Sameer Dhalla, Ellen M. Stein, Linda A. Lee, Laura A. Miriel, Mark L. Van Natta, Madhusudan Grover, Gianrico Farrugia, James Tonascia, Frank A. Hamilton, Henry P. Parkman, Nata DeVole, Karen Earle, Kjersti Kirkeby, Candice Lee, Mimi Lin, Katie Ponting, Gloria Yee, Pankaj Jay Pasricha, Ellen Stein, Yale Kim, Gotzone Garay, Chiara Orlando, Alan Mauer, Perry Orthey, Amiya Palit, Sean Connery, Yvette Gomez, Roberta Romero, Natalia Vega, Ben Alvarado, Lisa Hatter, Ronna Howard, Lindsay Nowotny, William Herman, Andrew Kraftson, Amy E. Rothberg, Sophanara Wootten, Lynn Baxter, Anya Brown, Paula Stuart, Samantha Culler, Cheryl Bernard, Frank Hamilton, Jose Serrano, Stephen James, Rebecca Torrance, Sherry Hall, Patricia Belt, John Dodge, Michele Donithan, Erin Hallinan, Milana Isaacson, Patrick K. May, Laura Miriel, Alice Sternberg, Mark Van Natta, Annette Wagoner, and Laura Wilson
- Subjects
Adult ,Male ,medicine.medical_specialty ,Gastroparesis ,Nausea ,Visual analogue scale ,Vomiting ,Morpholines ,Placebo ,Gastroenterology ,Article ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Double-Blind Method ,law ,Internal medicine ,Medicine ,Humans ,Adverse effect ,Aprepitant ,Hepatology ,business.industry ,Middle Aged ,medicine.disease ,Treatment Outcome ,030220 oncology & carcinogenesis ,Anesthesia ,Chronic Disease ,Antiemetics ,030211 gastroenterology & hepatology ,Female ,medicine.symptom ,business ,medicine.drug - Abstract
Background & Aims There are few effective treatments for nausea and other symptoms in patients with gastroparesis and related syndromes. We performed a randomized trial of the ability of the neurokinin-1 receptor antagonist aprepitant to reduce symptoms in patients with chronic nausea and vomiting caused by gastroparesis or gastroparesis-like syndrome. Methods We conducted a 4-week multicenter, double-masked trial of 126 patients with at least moderate symptoms of chronic nausea and vomiting of presumed gastric origin for a minimum of 6 months. Patients were randomly assigned to groups given oral aprepitant (125 mg/day, n = 63) or placebo (n = 63). The primary outcome from the intention-to-treat analysis was reduction in nausea, defined as a decrease of 25 mm or more, or absolute level below 25 mm, on a daily patient-reported 0-to-100 visual analog scale (VAS) of nausea severity. We calculated relative risks of nausea improvement using stratified Cochran-Mental-Haenszel analysis. Results Aprepitant did not reduce symptoms of nausea, based on the primary outcome measure (46% reduction in the VAS score in the aprepitant group vs 40% reduction in the placebo group; relative risk, 1.2; 95% CI, 0.8–1.7) ( P = .43). However, patients in the aprepitant group had significant changes in secondary outcomes such as reduction in symptom severity (measured by the 0–5 Gastroparesis Clinical Symptom Index) for nausea (1.8 vs 1.0; P = .005), vomiting (1.6 vs 0.5; P = .001), and overall symptoms (1.3 vs 0.7; P = .001). Adverse events, predominantly mild or moderate in severity grade, were more common in aprepitant (22 of 63 patients, 35% vs 11 of 63, 17% in the placebo group) ( P = .04). Conclusions In a randomized trial of patients with chronic nausea and vomiting caused by gastroparesis or gastroparesis-like syndrome, aprepitant did not reduce the severity of nausea when reduction in VAS score was used as the primary outcome. However, aprepitant had varying effects on secondary outcomes of symptom improvement. These findings support the need to identify appropriate patient outcomes for trials of therapies for gastroparesis, including potential additional trials for aprepitant. ClinicalTrials.gov no: NCT01149369.
- Published
- 2017