支气管肺泡灌洗液宏基因组下一代测序与传统微生物学检测对重症肺炎病原体鉴定及预后的临床价值（NT-BALF）：一项前瞻性多中心随机临床试验研究方案。

The clinical value of mNGS of bronchoalveolar lavage fluid versus traditional microbiological tests for pathogen identification and prognosis of severe pneumonia (NT-BALF):study protocol for a prospective multi-center randomized clinical trial.

机构信息

Emergency Department, The State Key Laboratory for Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

出版信息

Trials. 2024 Apr 22;25(1):276. doi: 10.1186/s13063-024-08112-x.

DOI:10.1186/s13063-024-08112-x

PMID:38650051

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11036641/

Abstract

BACKGROUND

Early, rapid, and accurate pathogen diagnosis can help clinicians select targeted treatment options, thus improving prognosis and reducing mortality rates of severe pneumonia. Metagenomic next-generation sequencing (mNGS) has a higher sensitivity and broader pathogen spectrum than traditional microbiological tests. However, the effects of mNGS-based antimicrobial treatment procedures on clinical outcomes and cost-effectiveness in patients with severe pneumonia have not been evaluated.

METHODS

This is a regional, multi-center, open, prospective, randomized controlled trial to evaluate that whether the combination of mNGS and traditional testing methods could decrease 28-day call-cause mortality with moderate cost-effectiveness. A total of 192 patients with severe pneumonia will be recruited from four large tertiary hospitals in China. Bronchoalveolar lavage fluid will be obtained in all patients and randomly assigned to the study group (mNGS combined with traditional microbiological tests) or the control group (traditional microbiological tests only) in a 1:1 ratio. Individualized antimicrobial treatment and strategy will be selected according to the analysis results. The primary outcome is 28-day all-cause mortality. The secondary outcomes are ICU and hospital length of stay (LOS), ventilator-free days and ICU-free days, consistency between mNGS and traditional microbiological tests, detective rate of mNGS and traditional microbiological tests, turn-out time, time from group allocation to start of treatment, duration of vasopressor support, types and duration of anti-infective regimens, source of drug-resistant bacteria or fungi, and ICU cost.

DISCUSSION

The clinical benefits of mNGS are potentially significant, but its limitations should also be considered.

TRIAL REGISTRATION

ChineseClinicalTrialRegistry.org, ChiCTR2300076853. Registered on 22 October 2023.

摘要

背景

早期、快速、准确的病原体诊断有助于临床医生选择靶向治疗方案，从而改善严重肺炎的预后并降低死亡率。宏基因组下一代测序（mNGS）比传统的微生物学检测具有更高的灵敏度和更广泛的病原体谱。然而，基于 mNGS 的抗菌治疗方案对严重肺炎患者的临床结局和成本效益的影响尚未得到评估。

方法

这是一项区域性、多中心、开放、前瞻性、随机对照试验，旨在评估 mNGS 与传统检测方法相结合是否能以适度的成本效益降低 28 天呼叫病因死亡率。总共将从中国的四家大型三级医院招募 192 名严重肺炎患者。所有患者均采集支气管肺泡灌洗液，并按 1:1 的比例随机分配到研究组（mNGS 联合传统微生物学检测）或对照组（仅传统微生物学检测）。根据分析结果选择个体化抗菌治疗和策略。主要结局是 28 天全因死亡率。次要结局是 ICU 和住院 LOS、无呼吸机天数和 ICU 无天数、mNGS 与传统微生物学检测的一致性、mNGS 和传统微生物学检测的检出率、周转时间、从分组到开始治疗的时间、血管加压支持持续时间、抗感染方案的类型和持续时间、耐药菌或真菌的来源以及 ICU 成本。