危重症患者逐步肠内营养替代蛋白质方案（REPLENISH）随机临床试验的统计分析计划。

Statistical analysis plan for the replacing protein via enteral nutrition in a stepwise approach in critically ill patients (REPLENISH) randomized clinical trial.

机构信息

Intensive Care Department, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, King Abdullah International Medical Research Center, ICU, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.

King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.

出版信息

Trials. 2024 May 2;25(1):296. doi: 10.1186/s13063-024-08105-w.

DOI:10.1186/s13063-024-08105-w

PMID:38698442

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11064302/

Abstract

BACKGROUND

The optimal amount and timing of protein intake in critically ill patients are unknown. REPLENISH (Replacing Protein via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial evaluates whether supplemental enteral protein added to standard enteral nutrition to achieve a high amount of enteral protein given from ICU day five until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve a moderate amount of enteral protein would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients.

METHODS

In this multicenter randomized trial, critically ill patients will be randomized to receive supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition to achieve a high amount of enteral protein (range of 2-2.4 g/kg/day) or no supplemental enteral protein to achieve a moderate amount of enteral protein (0.8-1.2 g/kg/day). The primary outcome is 90-day all-cause mortality; other outcomes include functional and health-related quality-of-life assessments at 90 days. The study sample size of 2502 patients will have 80% power to detect a 5% absolute risk reduction in 90-day mortality from 30 to 25%. Consistent with international guidelines, this statistical analysis plan specifies the methods for evaluating primary and secondary outcomes and subgroups. Applying this statistical analysis plan to the REPLENISH trial will facilitate unbiased analyses of clinical data.

CONCLUSION

Ethics approval was obtained from the institutional review board, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia (RC19/414/R). Approvals were also obtained from the institutional review boards of each participating institution. Our findings will be disseminated in an international peer-reviewed journal and presented at relevant conferences and meetings.

TRIAL REGISTRATION

ClinicalTrials.gov, NCT04475666 . Registered on July 17, 2020.

摘要

背景

目前仍不清楚危重症患者的最佳蛋白质摄入量和时间。REPLENISH（逐步通过肠内营养补充蛋白质以补充危重症患者）试验评估与不给予补充性肠内蛋白质以实现中等量肠内蛋白质相比，在重症监护病房第五天至重症监护病房出院或重症监护病房第 90 天给予补充性肠内蛋白质以达到较高量肠内蛋白质（2-2.4 g/kg/天）是否会降低所有原因 90 天死亡率在接受机械通气的成年危重症患者中。

方法

在这项多中心随机试验中，危重症患者将被随机分配接受补充性肠内蛋白质（1.2 g/kg/天）以达到较高量肠内蛋白质（2-2.4 g/kg/天），或不给予补充性肠内蛋白质以达到中等量肠内蛋白质（0.8-1.2 g/kg/天）。主要结局是 90 天全因死亡率；其他结局包括 90 天的功能和健康相关生活质量评估。研究样本量为 2502 例患者，将有 80%的效力检测 90 天死亡率从 30%降低到 25%的绝对风险降低 5%。符合国际指南，本统计分析计划规定了评估主要和次要结局以及亚组的方法。将此统计分析计划应用于 REPLENISH 试验将有助于对临床数据进行无偏分析。