Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression - A randomized controlled trial
Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression - A randomized controlled trial
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DOI：
10.1001/jama.289.21.2819
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发表时间：
2003-06-04
影响因子：
120.7
通讯作者：
Thal, LJ
中科院分区：
文献类型：
--
作者：
Aisen, PS;Schafer, KA;Thal, LJ
实验室证据表明，炎症机制有助于阿尔茨海默病（AD）的神经元损伤，沿着流行病学证据，目的探讨选择性环氧合酶（考克斯）-2抑制剂治疗是否能有效地改善慢性前列腺炎的临床疗效。（罗非昔布）或传统的非选择性NSAID（萘普生）减缓轻度至中度AD患者的认知功能下降。设计多中心、随机、双盲、安慰剂对照、平行组试验，设置40个附属于阿尔茨海默氏病合作研究联盟的门诊治疗中心：参与者从1999年12月至2000年11月使用诊所人群、社区医生的转诊和当地广告招募轻度至中度AD（简易精神状态检查评分为13-26）的参与者。允许稳定使用胆碱酯酶抑制剂、雌激素、低剂量阿司匹林和维生素E。患有可能对研究药物有反应的炎症性疾病的参与者被排除。474名参与者筛选，351人enrolled.Interventions一天一次罗非昔布，25毫克，或每天两次的那普利钠，220毫克，或placebo.Main结果Measures主要结果措施是1年的变化阿尔茨海默病评估量表认知（ADAS-Cog）子量表评分。次要结果测量包括临床痴呆评定量表、神经精神量表、生活质量-AD和达到显著终点的时间（ADAS-Cog评分较基线下降4分，全球临床痴呆评定量表恶化1级，ADCS日常生活活动量表下降15分，机构化，结果接受那普利生（5.8 [8.0]）或罗非昔布（7.6 [7.7]）治疗的受试者的ADAS-Cog评分的1年平均（SD）变化与接受安慰剂治疗的受试者的变化（5.7 [8.2]）无显著差异。次要分析结果显示，两种治疗均无一致获益。疲劳，头晕，高血压是更常见的活性药物组，更严重的不良事件被发现在活性治疗组比在安慰剂group.Conclusion本研究的结果表明，罗非昔布或低剂量的萘普生不减缓认知功能下降的患者轻度至中度AD。
Context Laboratory evidence that inflammatory mechanisms contribute to neuronal injury in Alzheimer disease (AD), along with epidemiological evidence, suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) may favorably influence the course of the disease.Objective To determine whether treatment with a selective cyclooxygenase (COX) -2 inhibitor (rofecoxib) or a traditional nonselective NSAID (naproxen) slows cognitive decline in patients with mild-to-moderate AD.Design Multicenter, randomized, double-blind, placebo-controlled, parallel group trial, with 1-year exposure to study medications.Setting Forty ambulatory treatment centers affiliated with the Alzheimer's Disease Cooperative Study consortium:Participants Participants with mild-to-moderate AD (Mini-Mental State Examination score of 13-26) were recruited from December 1999 to November 2000 using clinic populations, referrals from community physicians, and local advertising. Stable use of cholinesterase inhibitors, estrogen, low-dose aspirin, and vitamin E was allowed. Participants with inflammatory diseases that might respond to the study medications were excluded. Of 474 participants screened, 351 were enrolled.Interventions Once-daily rofecoxib, 25 mg, or twice-daily naproxen sodium, 220 mg, or placebo.Main Outcome Measures The primary outcome measure was the 1-year change in the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) subscale score. Secondary outcome measures included the Clinical Dementia Rating scale sum-of-boxes the Neuropsychiatric Inventory, the Quality of Life-AD and the time to attainment of significant end points (4-point decline from baseline ADAS-Cog score, 1-step worsening on the global Clinical Dementia Rating scale, 15-point decline on the ADCS activities of daily living inventory, institutionalization, or death).Results The 1-year mean (SD) change in ADAS-Cog scores in participants treated with naproxen (5.8 [8.0]) or rofecoxib (7.6 [7.7]) was not significantly different from the change in participants treated with placebo (5.7 [8.2]). Results of secondary analyses showed no consistent benefit of either treatment. Fatigue, dizziness, and hypertension were more commonly reported in the active drug groups, and more serious adverse events were found in the active treatment group than in the placebo group.Conclusion The results of this study indicate that rofecoxib or low-dose naproxen does not slow cognitive decline in patients with mild-to-moderate AD.