部分口服抗生素治疗细菌性脑脓肿：一项开放标签随机非劣效性试验（ORAL）。
Partial oral antibiotic treatment for bacterial brain abscess: an open-label randomized non-inferiority trial (ORAL).
机构信息
Department of Infectious Diseases, Aalborg University Hospital, Mølleparkvej 4, 9000, Aalborg, Denmark.
European Society for Clinical Microbiology and Infectious Diseases Study Group of Infections in the Brain (ESCMID), Basel, Switzerland.
出版信息
Trials. 2021 Nov 12;22(1):796. doi: 10.1186/s13063-021-05783-8.
BACKGROUND
The advised standard treatment for bacterial brain abscess following surgery is 6 to 8 weeks of intravenous (IV) antibiotic treatment, but an early switch to oral antibiotic treatment has been suggested to be equally effective.
METHODS
This investigator-initiated, international, multi-center, parallel group, open-label, randomized (1:1 allocation) controlled trial will examine if oral treatment after 2 weeks of IV antibiotic therapy is non-inferior to standard 6-8 weeks of IV antibiotics for bacterial brain abscess in adults (≥ 18 years of age). The study will be conducted at hospitals across Denmark, the Netherlands, France, Australia, and Sweden. Exclusion criteria are severe immunocompromise or impaired gastro-intestinal absorption, pregnancy, device-related brain abscesses, and brain abscess caused by nocardia, tuberculosis, or Pseudomonas spp. The primary objective is a composite endpoint at 6 months after randomization consisting of all-cause mortality, intraventricular rupture of brain abscess, unplanned re-aspiration or excision of brain abscess, relapse, or recurrence. The primary endpoint will be adjudicated by an independent blinded endpoint committee. Secondary outcomes include extended Glasgow Outcome Scale scores and all-cause mortality at end of treatment as well as 3, 6, and 12 months since randomization, completion of assigned treatment, IV catheter associated complications, durations of admission and antibiotic treatment, severe adverse events, quality of life scores, and cognitive evaluations. The planned sample size is 450 patients for a one-sided alpha of 0.025 and a power of 90% to exclude a difference in favor of standard treatment of more than 10%. Date of initiation of first study center was November 3, 2020, with active recruitment for 3 years and follow-up for 1 year of all patients.
DISCUSSION
The results of this study may guide future recommendations for treatment of bacterial brain abscess. If early transition to oral antibiotics proves non-inferior to standard IV treatment, this will provide considerable health and costs benefits.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04140903, first registered 28.10.2019. EudraCT number: 2019-002845-39, first registered 03.07.2019.
背景
手术后细菌性脑脓肿的建议标准治疗是 6 至 8 周的静脉（IV）抗生素治疗，但有研究建议早期转换为口服抗生素治疗同样有效。
方法
本项由研究者发起的国际多中心平行组开放标签随机（1:1 分配）对照试验将研究在静脉抗生素治疗 2 周后进行口服治疗是否不劣于成人（≥ 18 岁）细菌性脑脓肿的标准 6-8 周静脉抗生素治疗。该研究将在丹麦、荷兰、法国、澳大利亚和瑞典的医院进行。排除标准为严重免疫功能低下或胃肠吸收受损、妊娠、器械相关脑脓肿以及诺卡氏菌、结核分枝杆菌或假单胞菌引起的脑脓肿。主要终点是随机分组后 6 个月的复合终点，包括全因死亡率、脑脓肿脑室内破裂、脑脓肿计划外再次抽吸或切除、复发或再发。主要终点将由一个独立的盲法终点委员会裁决。次要结局包括扩展的格拉斯哥结局量表评分和治疗结束时的全因死亡率，以及随机分组后 3、6 和 12 个月、完成指定治疗、静脉导管相关并发症、住院和抗生素治疗时间、严重不良事件、生活质量评分和认知评估。计划的样本量为 450 例患者，单侧 α 值为 0.025，效力为 90%，以排除标准治疗更有利的差异超过 10%。首个研究中心于 2020 年 11 月 3 日开始启动，所有患者的招募期为 3 年，随访期为 1 年。
讨论
本研究结果可能为细菌性脑脓肿的治疗提供未来建议。如果早期转为口服抗生素被证明不劣于标准 IV 治疗，这将带来显著的健康和成本效益。
试验注册
ClinicalTrials.gov NCT04140903，首次注册于 2019 年 10 月 28 日。EudraCT 编号：2019-002845-39，首次注册于 2019 年 7 月 3 日。
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