Australasian Malignant PLeural Effusion (AMPLE)-4 trial: study protocol for a multi-centre randomised trial of topical antibiotics prophylaxis for infections of indwelling pleural catheters

Abstract Background Malignant pleural effusion (MPE) is a debilitating condition as it commonly causes disabling breathlessness and impairs quality of life (QoL). Indwelling pleural catheter (IPC) offers an effective alternative for the management of MPE. However, IPC-related infections remain a significant concern and there are currently no long-term strategies for their prevention. The Australasian Malignant PLeural Effusion (AMPLE)-4 trial is a multicentre randomised trial that evaluates the use of topical mupirocin prophylaxis (vs no mupirocin) to reduce catheter-related infections in patients with MPE treated with an IPC. Methods A pragmatic, multi-centre, open-labelled, randomised trial. Eligible patients with MPE and an IPC will be randomised 1:1 to either regular topical mupirocin prophylaxis or no mupirocin (standard care). For the interventional arm, topical mupirocin will be applied around the IPC exit-site after each drainage, at least twice weekly. Weekly follow-up via phone calls or in person will be conducted for up to 6 months. The primary outcome is the percentage of patients who develop an IPC-related (pleural, skin, or tract) infection between the time of catheter insertion and end of follow-up period. Secondary outcomes include analyses of infection (types and episodes), hospitalisation days, health economics, adverse events, and survival. Subject to interim analyses, the trial will recruit up to 418 participants. Discussion Results from this trial will determine the efficacy of mupirocin prophylaxis in patients who require IPC for MPE. It will provide data on infection rates, microbiology, and potentially infection pathways associated with IPC-related infections. Ethics and dissemination Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee has approved the study (RGS0000005920). Results will be published in peer-reviewed journals and presented at scientific conferences. Trial registration Australia New Zealand Clinical Trial Registry ACTRN12623000253606. Registered on 9 March 2023.摘要 背景 恶性胸腔积液（Malignant pleural effusion, MPE）是一种致残性疾病，常引发严重呼吸困难并损害患者生活质量（QoL）。留置胸膜导管（Indwelling pleural catheter, IPC）为恶性胸腔积液的临床管理提供了有效替代方案。然而，导管相关感染仍是突出的临床关切问题，目前尚无针对此类感染的长期预防策略。澳大拉西亚恶性胸腔积液（Australasian Malignant PLeural Effusion, AMPLE）-4试验是一项多中心随机对照试验，旨在评估局部莫匹罗星预防方案（对比不使用莫匹罗星）对接受留置胸膜导管治疗的恶性胸腔积液患者减少导管相关感染的效果。 方法 本研究为务实型多中心开放标签随机对照试验。符合入组标准的恶性胸腔积液且已留置胸膜导管的患者将以1:1的比例随机分配至常规局部莫匹罗星预防组或不使用莫匹罗星的标准治疗组。干预组患者需在每次胸腔引流后，于导管出口周围涂抹局部莫匹罗星，涂抹频次至少为每周两次。研究将通过电话或面对面随访的方式进行每周一次的随访，随访时长最长可达6个月。主要结局指标为从导管置入至随访期结束期间，发生导管相关（胸膜、皮肤或隧道）感染的患者比例。次要结局指标包括感染类型与发作次数、住院天数、卫生经济学分析、不良事件及生存率。经中期分析后，本试验计划招募至多418名受试者。 讨论 本试验结果将明确莫匹罗星预防方案对需接受留置胸膜导管治疗的恶性胸腔积液患者的有效性，同时将提供导管相关感染的感染率、微生物学特征及潜在感染途径相关数据。 伦理与传播 查尔斯爵士盖尔德与奥斯本帕克医疗集团人类研究伦理委员会已批准本研究（审批编号：RGS0000005920）。研究结果将发表于同行评审期刊，并在学术会议上进行展示。试验注册信息：澳大利亚新西兰临床试验注册中心ACTRN12623000253606，注册日期为2023年3月9日。