比较创伤患者限制性与宽松性氧疗策略：TRAUMOX2 试验-统计分析计划。

Comparing restrictive versus liberal oxygen strategies for trauma patients: The TRAUMOX2 trial-Statistical analysis plan.

机构信息

Department of Anaesthesia, Centre of Head and Orthopaedics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

The Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.

出版信息

Acta Anaesthesiol Scand. 2023 Jul;67(6):829-838. doi: 10.1111/aas.14230. Epub 2023 Mar 28.

DOI:10.1111/aas.14230

PMID:36906804

Abstract

BACKGROUND

The international advanced trauma life support guidelines recommend that all severely injured trauma patients receive supplemental oxygen based on very limited evidence. The TRAUMOX2 trial randomises adult trauma patients to a restrictive or liberal oxygen strategy for 8 h. The primary composite outcome consists of 30-day mortality and/or development of major respiratory complications (pneumonia and/or acute respiratory distress syndrome). This manuscript presents the statistical analysis plan for TRAUMOX2.

METHODS

Patients are randomised 1:1 in variable block sizes of four, six and eight, stratified by including centre (pre-hospital base or trauma centre) and tracheal intubation at inclusion. The trial will include 1420 patients to be able to detect a 33% relative risk reduction with the restrictive oxygen strategy of the composite primary outcome with 80% power at the 5% significance level. We will conduct modified intention-to-treat analyses on all randomised patients and per-protocol analyses for the primary composite outcome and key secondary outcomes. The primary composite outcome and two key secondary outcomes will be compared between the two allocated groups using logistic regression reported as odds ratios with 95% confidence intervals adjusted for the stratification variables as in the primary analysis. A p-value below 5% will be considered statistically significant. A Data Monitoring and Safety Committee has been established to conduct interim analyses after inclusion of 25% and 50% of the patients.

CONCLUSION

This statistical analysis plan of the TRAUMOX2 trial will minimise bias and add transparency to the statistics applied in the analysis of the trial. The results will add evidence on restrictive and liberal supplemental oxygen strategies for trauma patients.

TRIAL REGISTRATION

EudraCT number: 2021-000556-19; ClinicalTrials.gov identifier: NCT05146700 (date of registration: 7 December 2021).

摘要

背景

国际先进创伤生命支持指南建议所有严重创伤患者根据非常有限的证据接受补充氧气。TRAUMOX2 试验将成年创伤患者随机分配到限制或宽松的氧疗策略中 8 小时。主要复合结局包括 30 天死亡率和/或主要呼吸并发症（肺炎和/或急性呼吸窘迫综合征）的发展。本文介绍了 TRAUMOX2 的统计分析计划。

方法

患者以 4、6 和 8 的可变块大小 1:1 随机分组，分层因素包括纳入中心（院前基地或创伤中心）和纳入时气管插管。该试验将纳入 1420 例患者，以便能够以 80%的效力在 5%的显著性水平上检测到限制性氧疗策略对复合主要结局的 33%相对风险降低。我们将对所有随机患者进行修改后的意向治疗分析，并对主要复合结局和关键次要结局进行方案分析。主要复合结局和两个关键次要结局将使用逻辑回归进行比较，报告为优势比，并根据主要分析中的分层变量进行调整。p 值低于 5%将被认为具有统计学意义。已成立数据监测和安全委员会，以在纳入 25%和 50%的患者后进行中期分析。