Portsmouth Simon, Echols Roger, Toyoizumi Kiichiro, Tillotson Glenn, Nagata Tsutae Den
Shionogi Inc., 300 Campus Drive, Florham Park, NJ 07932, USA.
Infectious Disease Drug Development Consulting, LLC, Easton, CT, USA.
Ther Adv Infect Dis. 2021 Nov 24;8:20499361211058257. doi: 10.1177/20499361211058257. eCollection 2021 Jan-Dec.
The APEKS-cUTI study demonstrated the non-inferiority of cefiderocol to imipenem-cilastatin in the primary endpoint of the composite of clinical and microbiological outcome in patients with complicated urinary tract infections (cUTIs). We piloted a structured patient interview (SPI) to evaluate clinical outcomes based on patient-reported symptoms while conducting this pivotal randomized, double-blind, phase-2 study. The objectives were to assess the value of the SPI, using its performance relative to physician assessment, and also to strengthen the value of patient-reported measures in conducting clinical trials for cUTI treatment.
In addition to the protocol-defined clinical and microbiological outcomes, patients randomized in the APEKS-cUTI study were interviewed by the investigator or qualified study personnel at screening/baseline, early assessment (EA), end of treatment (EOT), test of cure (TOC), and follow-up (FUP). The 14-element questionnaire graded cUTI symptoms as absent or present, and if present, as mild, moderate, or severe. Changes in post-baseline symptoms based on patients' responses were rated by the interviewer. The overall clinical outcome was evaluated based on the responses provided by patients at each time point.
Among the 371 patients in the modified intention-to-treat population, the rate of SPI completion in each treatment arm exceeded 90% at each time point. SPI-assessed clinical cure rates were 89.7% in the cefiderocol arm and 84.9% in the imipenem-cilastatin arm. There was substantial agreement between SPI evaluation and investigator global assessment of clinical outcome at TOC and FUP, with lower agreement at EA and EOT.
This analysis suggests that patient-reported symptoms can be effectively captured in hospitalized patients with cUTI in a clinical trial setting. Development of a validated patient-reported outcome for use in such a setting is warranted.
NCT02321800 (registered on 22 December 2014).
APEKS-cUTI研究表明，在复杂性尿路感染（cUTI）患者的临床和微生物学综合主要终点方面，头孢地尔与亚胺培南-西司他丁相比具有非劣效性。在开展这项关键的随机、双盲、2期研究时，我们试点了一项结构化患者访谈（SPI），以根据患者报告的症状评估临床结局。目的是评估SPI的价值，将其表现与医生评估进行比较，同时强化患者报告指标在cUTI治疗临床试验中的价值。
除了方案定义的临床和微生物学结局外，APEKS-cUTI研究中随机分组的患者在筛查/基线、早期评估（EA）、治疗结束（EOT）、治愈检测（TOC）和随访（FUP）时，由研究者或合格的研究人员进行访谈。这份包含14项内容的问卷将cUTI症状分为不存在或存在，若存在则分为轻度、中度或重度。访谈者根据患者的回答对基线后症状的变化进行评分。根据患者在每个时间点提供的回答评估总体临床结局。
在改良意向性治疗人群的371例患者中，每个治疗组在每个时间点的SPI完成率均超过90%。头孢地尔组SPI评估的临床治愈率为89.7%，亚胺培南-西司他丁组为84.9%。在TOC和FUP时，SPI评估与研究者对临床结局的整体评估之间存在高度一致性，而在EA和EOT时一致性较低。
该分析表明，在临床试验环境中，cUTI住院患者的患者报告症状能够得到有效获取。有必要开发一种经过验证的患者报告结局用于此类情况。
NCT02321800（于2014年12月22日注册）
