Pasricha Pankaj J, Yates Katherine P, Sarosiek Irene, McCallum Richard W, Abell Thomas L, Koch Kenneth L, Nguyen Linda Anh B, Snape William J, Hasler William L, Clarke John O, Dhalla Sameer, Stein Ellen M, Lee Linda A, Miriel Laura A, Van Natta Mark L, Grover Madhusudan, Farrugia Gianrico, Tonascia James, Hamilton Frank A, Parkman Henry P
Johns Hopkins University School of Medicine, Baltimore, MD.
Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
Gastroenterology. 2018 Jan;154(1):65-76.e11. doi: 10.1053/j.gastro.2017.08.033. Epub 2017 Oct 28.
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.
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.
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).
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.
对于胃轻瘫及相关综合征患者的恶心和其他症状，几乎没有有效的治疗方法。我们开展了一项随机试验，以研究神经激肽-1受体拮抗剂阿瑞匹坦减轻由胃轻瘫或类胃轻瘫综合征引起的慢性恶心和呕吐患者症状的能力。
我们对126例至少有中度慢性恶心和呕吐症状（推测源于胃部）且症状持续至少6个月的患者进行了为期4周的多中心双盲试验。患者被随机分为口服阿瑞匹坦组（125毫克/天，n = 63）和安慰剂组（n = 63）。意向性分析的主要结局是恶心减轻，定义为在患者每日报告的0至100视觉模拟量表（VAS）上恶心严重程度降低25毫米或更多，或绝对水平低于25毫米。我们使用分层Cochran-Mental-Haenszel分析计算恶心改善的相对风险。
根据主要结局指标，阿瑞匹坦并未减轻恶心症状（阿瑞匹坦组VAS评分降低46%，安慰剂组降低40%；相对风险为1.2；95%置信区间为0.8 - 1.7）（P = 0.43）。然而，阿瑞匹坦组患者在次要结局方面有显著变化，如恶心症状严重程度降低（通过0 - 5胃轻瘫临床症状指数衡量）（1.8对1.0；P = 0.005）、呕吐（1.6对0.5；P = 0.001）和总体症状（1.3对0.7；P = 0.001）。不良事件主要为轻度或中度严重程度分级，在阿瑞匹坦组更常见（63例患者中有22例，35%，而安慰剂组63例中有11例，17%）（P = 0.04）。
在一项针对由胃轻瘫或类胃轻瘫综合征引起的慢性恶心和呕吐患者的随机试验中，以VAS评分降低作为主要结局时，阿瑞匹坦并未减轻恶心的严重程度。然而，阿瑞匹坦对症状改善的次要结局有不同影响。这些发现支持了为胃轻瘫治疗试验确定合适患者结局的必要性，包括可能对阿瑞匹坦进行的额外试验。ClinicalTrials.gov编号：NCT01149369。
