一项针对复杂性肠球菌菌血症患者，比较 7 天与 14 天抗生素疗程的有效性和安全性的随机、开放标签、非劣效性临床试验：INTENSE 试验方案。

Randomised, open-label, non-inferiority clinical trial on the efficacy and safety of a 7-day vs 14-day course of antibiotic treatment for uncomplicated enterococcal bacteraemia: the INTENSE trial protocol.

机构信息

Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Sevilla, Spain.

Universidad de Sevilla, Instituto de Biomedicina de Sevilla (IBiS)/CSIC; CIBERINFEC, Sevilla, Spain.

出版信息

BMJ Open. 2023 Sep 6;13(9):e075699. doi: 10.1136/bmjopen-2023-075699.

DOI:10.1136/bmjopen-2023-075699

PMID:37673453

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10496718/

Abstract

INTRODUCTION

spp is responsible for 8%-15% of total bacteraemias with an associated global mortality around 23%-30%. Regarding the clinical management of enterococcal bacteraemia, the evidence on the duration of antibiotic treatment is scarce and the studies do not discriminate between complicated and uncomplicated bacteraemia.

METHODS

The INTENSE study is a multicentre, open-label, randomised, pragmatic, phase-IV clinical trial to demonstrate the non-inferiority of a 7-day vs 14-day course for the treatment of uncomplicated enterococcal bacteraemia and incorporating the early switching to oral antibiotics when feasible. The primary efficacy endpoint is the clinical cure at day 30±2 after the end of the treatment. Secondary endpoints will include the rate of relapse or infective endocarditis, length of stay, duration of intravenous therapy, infection and the evaluation of the safety of both treatment arms through the recording and analysis of adverse events. For a 6% non-inferiority margin and considering a 5% withdrawal rate, 284 patients will be included.

ANALYSIS

The difference in proportions with one-sided 95% CIs will be calculated for the clinical cure rate using the control group as reference. For secondary categorical endpoints, a similar analysis will be performed and Mann-Whitney U-test will be used to compare median values of quantitative variables. A superiority analysis applying the response adjusted for days of antibiotic risk will be performed if there were incidents in recruitment; will allow obtaining results with 194 patients recruited.

ETHICS AND DISSEMINATION

The study has obtained the authorisation from the Spanish Regulatory Authority, the approval of the ethics committee and the agreement of the directors of each centre. Data will be published in peer-reviewed journals.

TRIAL REGISTRATION NUMBER

NCT05394298.

摘要

简介

spp 导致 8%-15%的菌血症，其全球死亡率约为 23%-30%。关于肠球菌菌血症的临床管理，抗生素治疗持续时间的证据很少，而且研究没有区分复杂菌血症和不复杂菌血症。

方法

INTENSE 研究是一项多中心、开放标签、随机、实用、四期临床试验，旨在证明 7 天与 14 天疗程治疗不复杂肠球菌菌血症的非劣效性，并在可行时尽早转为口服抗生素。主要疗效终点是治疗结束后第 30±2 天的临床治愈率。次要终点将包括复发或感染性心内膜炎的发生率、住院时间、静脉治疗持续时间、感染率以及通过记录和分析不良事件评估两种治疗方案的安全性。考虑到 6%的非劣效性边界和 5%的退出率，将纳入 284 名患者。