University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Am J Gastroenterol. 2013 Mar;108(3):392-400. doi: 10.1038/ajg.2012.467. Epub 2013 Feb 12.
Because of the limitations of randomized controlled trials (RCTs) and observational studies, a prospective, randomized, open-label, blinded endpoint (PROBE) study may be an appropriate alternative, as the design allows the assessment of clinical outcomes in clinical practice settings. The Gastrointestinal (GI) Randomized Event and Safety Open-Label Nonsteroidal Anti-inflammatory Drug (NSAID) Study (GI-REASONS) was designed to reflect standard clinical practice while including endpoints rigorously evaluated by a blinded adjudication committee. The objective of this study was to assess if celecoxib is associated with a lower incidence of clinically significant upper and/or lower GI events than nonselective NSAIDs (nsNSAIDs) in standard clinical practice.
This was a PROBE study carried out at 783 centers in the United States, where a total of 8,067 individuals aged ≥ 55 years, requiring daily NSAIDs to treat osteoarthritis, participated. The participants were randomized to celecoxib or nsNSAIDs (1:1) for 6 months and stratified by Helicobacter pylori status. Treatment doses could be adjusted as per the United States prescribing information; patients randomized to nsNSAIDs could switch between nsNSAIDs; crossover between treatment arms was not allowed, and patients requiring aspirin at baseline were excluded. The primary outcome was the incidence of clinically significant upper and/or lower GI events.
Significantly more nsNSAID users met the primary endpoint (2.4% (98/4,032) nsNSAID patients and 1.3% (54/4,035) celecoxib patients; odds ratio, 1.82 (95% confidence interval, 1.31-2.55); P = 0.0003). Moderate to severe abdominal symptoms were experienced by 94 (2.3%) celecoxib and 138 (3.4%) nsNSAID patients (P=0.0035). Other non-GI adverse events were similar between treatment groups. One limitation is the open-label design, which presents the possibility of interpretive bias.
Celecoxib was associated with a lower risk of clinically significant upper and/or lower GI events than nsNSAIDs. Furthermore, this trial represents a successful execution of a PROBE study, where therapeutic options and management strategies available in clinical practice were incorporated into the rigor of a prospective RCT.
由于随机对照试验（RCT）和观察性研究的局限性，前瞻性、随机、开放标签、盲终点（PROBE）研究可能是一种合适的替代方法，因为该设计允许在临床实践环境中评估临床结局。胃肠道（GI）随机事件和安全性开放标签非甾体抗炎药（NSAID）研究（GI-REASONS）旨在反映标准临床实践，同时由盲法裁决委员会严格评估终点。本研究的目的是评估塞来昔布与非选择性 NSAIDs（nsNSAIDs）相比，在标准临床实践中是否与较低的临床显著上消化道和/或下消化道事件发生率相关。
这是一项在美国 783 个中心进行的 PROBE 研究，共有 8067 名年龄≥55 岁、需要每日 NSAIDs 治疗骨关节炎的患者参与。这些患者被随机分配至塞来昔布或 nsNSAIDs（1:1），治疗时间为 6 个月，并按幽门螺杆菌状态分层。治疗剂量可根据美国处方信息进行调整；随机分配至 nsNSAIDs 的患者可在 nsNSAIDs 之间转换；不允许治疗组之间交叉，且基线时需要阿司匹林的患者被排除在外。主要结局是临床显著上消化道和/或下消化道事件的发生率。
nsNSAID 使用者更符合主要终点（2.4%（98/4032）nsNSAID 患者和 1.3%（54/4035）塞来昔布患者；比值比，1.82（95%置信区间，1.31-2.55）；P=0.0003）。94 例（2.3%）塞来昔布和 138 例（3.4%）nsNSAID 患者出现中度至重度腹部症状（P=0.0035）。两组之间其他非胃肠道不良事件相似。一个局限性是开放标签设计，这存在解释性偏倚的可能性。
塞来昔布与非选择性 NSAIDs 相比，上消化道和/或下消化道的临床显著事件风险较低。此外，本试验代表了 PROBE 研究的成功实施，其中纳入了临床实践中可用的治疗选择和管理策略，以严格执行前瞻性 RCT。
