短疗程术后抗生素治疗脊柱感染：前瞻性、随机、非盲、非劣效性试验（SASI 试验）方案。

Short postsurgical antibiotic therapy for spinal infections: protocol of prospective, randomized, unblinded, noninferiority trials (SASI trials).

机构信息

Department of Orthopedic Surgery, Balgrist University Hospital, Zurich, Switzerland.

University Spine Center Zürich, Balgrist University Hospital, Zurich, Switzerland.

出版信息

Trials. 2020 Feb 6;21(1):144. doi: 10.1186/s13063-020-4047-3.

DOI:10.1186/s13063-020-4047-3

PMID:32028985

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7006138/

Abstract

BACKGROUND

There are several open scientific questions regarding the optimal antibiotic treatment of spinal infections (SIs) with or without an implant. The duration of postsurgical antibiotic therapy is debated.

METHODS

We will perform two unblinded randomized controlled trials (RCTs). We hypothesize that shorter durations of systemic antibiotic therapy after surgery for SI are noninferior (10% margin, 80% power, α = 5%) to existing (long) treatment durations. The RCTs allocate the participants to two arms of 2 × 59 episodes each: 3 vs. 6 weeks of targeted postsurgical systemic antibiotic therapy for implant-free SIs or 6 vs. 12 weeks for implant-related SIs. This equals a total of 236 adult SI episodes (randomization scheme 1:1) with a minimal follow-up of 12 months. All participants receive concomitant multidisciplinary surgical, re-educational, internist, and infectious disease care. We will perform three interim analyses that are evaluated, in a blinded analysis, by an independent study data monitoring committee. Besides the primary outcome of remission, we will also assess adverse events of antibiotic therapy, changes of the patient's nutritional status, the influence of immune suppression, total costs, functional scores, and the timely evolution of the (surgical) wounds. We define infection as the presence of local signs of inflammation (pus, wound discharge, calor, and rubor) together with microbiological evidence of the same pathogen(s) in at least two intraoperative samples, and we define remission as the absence of clinical, laboratory, and/or radiological evidence of (former or new) infection.

DISCUSSION

Provided that there is adequate surgical debridement, both RCTs will potentially enable prescription of less antibiotics during the therapy of SI, with potentially less adverse events and reduced overall costs.

TRIAL REGISTRATION

ClinicalTrials.gov, NCT04048304. Registered on 5 August 2019.

PROTOCOL VERSION

2, 5 July 2019.

摘要

背景

对于伴有或不伴有植入物的脊柱感染（SI）的最佳抗生素治疗，存在一些尚未解决的科学问题。术后抗生素治疗的持续时间存在争议。

方法

我们将进行两项非盲随机对照试验（RCT）。我们假设，SI 手术后较短时间的系统抗生素治疗（10%的边界，80%的效力，α=5%）与现有的（长）治疗时间相比是非劣效的。这两项 RCT 将参与者分为两组，每组 59 例：无植入物的 SI 患者接受 3 周或 6 周的靶向术后系统性抗生素治疗，植入物相关的 SI 患者接受 6 周或 12 周的治疗。这相当于总共 236 例成人 SI 发作（随机分组 1:1），随访时间至少为 12 个月。所有参与者均接受多学科的手术、康复、内科和感染病治疗。我们将进行三次中期分析，由一个独立的数据监测委员会进行盲法分析。除了缓解的主要结局外，我们还将评估抗生素治疗的不良反应、患者营养状况的变化、免疫抑制的影响、总费用、功能评分以及（手术）伤口的及时愈合情况。我们将感染定义为局部炎症（脓液、伤口渗出物、发热和红肿）的存在，同时至少两个术中样本中有相同病原体的微生物学证据，并将缓解定义为无临床、实验室和/或影像学证据（以前或新）感染。