Department of Pharmacy Practice, Purdue University College of Pharmacy, West Lafayette, IN, USA.
Indiana University Center for Aging Research, Regenstrief Institute, Inc, Indianapolis, IN, USA.
Trials. 2024 Nov 22;25(1):788. doi: 10.1186/s13063-024-08618-4.
Older adults commonly experience chronic medical conditions and are at risk of cognitive impairment as a result of age, chronic comorbidity, and medications prescribed to manage multiple chronic conditions. Anticholinergic medications are common treatments for chronic conditions and have been repeatedly associated with poor cognitive outcomes, including delirium and dementia, in epidemiologic studies. However, no study has definitively evaluated the causal relationship between anticholinergics and cognition in a randomized controlled trial design. Utilizing our prior experience in deprescribing anticholinergic medications in various clinical environments, we designed an outpatient deprescribing intervention to prospectively test the potential causal relationship between anticholinergics and cognition in primary care older adults.
This cluster randomized clinical trial will be conducted to evaluate the impact of an anticholinergic deprescribing intervention compared to usual care on outcomes of cognition and safety in primary care older adults. Participants will include those aged 65 years and over, receiving primary care in the greater Indianapolis area, using a strong anticholinergic within the last 2 weeks or with evidence of high-risk exposure in the past year. Those excluded will have a diagnosis of Alzheimer's disease or related dementia, or serious mental illness. The trial plans to enroll 344 participants who will be cluster-randomized at the level of primary care physician to avoid contamination. Participants will complete outcome assessments every 6 months up to 2 years by blinded outcome assessors. The primary outcome of the study is a composite measure of cognition that includes domains assessing executive cognitive function, language, and memory. Secondary outcomes include patient-reported measures of pain intensity, depression, anxiety, sleep disturbance, and health-related quality of life.
The R2D2 trial will be the largest and longest prospective randomized trial testing the impact of an anticholinergic-specific deprescribing intervention on cognition in primary care older adults. Results could influence deprescribing methodology and provide new insight on the relationship between anticholinergics and cognition.
ClinicalTrials.gov NCT04270474. Registered on February 17, 2020.
老年人通常患有慢性疾病，并且由于年龄、慢性共病和用于治疗多种慢性疾病的药物，他们有认知障碍的风险。抗胆碱能药物是治疗慢性疾病的常用药物，在流行病学研究中，它们与认知不良结局（包括谵妄和痴呆）反复相关。然而，没有研究在随机对照试验设计中明确评估抗胆碱能药物与认知之间的因果关系。利用我们在各种临床环境中减少抗胆碱能药物使用的经验，我们设计了一个门诊药物减量干预措施，旨在前瞻性地测试初级保健老年人群中抗胆碱能药物与认知之间的潜在因果关系。
本项集群随机临床试验将评估与常规护理相比，抗胆碱能药物减量干预对初级保健老年患者认知和安全性结局的影响。参与者将包括年龄在 65 岁及以上、在印第安纳波利斯大都市区接受初级保健、在过去 2 周内使用强效抗胆碱能药物或过去 1 年内有高风险暴露证据的患者。排除标准为阿尔茨海默病或相关痴呆或严重精神疾病的诊断。该试验计划招募 344 名参与者，他们将按初级保健医生的水平进行集群随机分组，以避免交叉污染。参与者将由盲法结局评估者每 6 个月评估一次结局，最长 2 年。研究的主要结局是认知的综合测量，包括评估执行认知功能、语言和记忆的领域。次要结局包括患者报告的疼痛强度、抑郁、焦虑、睡眠障碍和健康相关生活质量的测量。
R2D2 试验将是最大和最长的前瞻性随机试验，测试初级保健老年人群中抗胆碱能药物特异性药物减量干预对认知的影响。结果可能会影响药物减量方法，并提供关于抗胆碱能药物与认知之间关系的新见解。
ClinicalTrials.gov NCT04270474。于 2020 年 2 月 17 日注册。
