Cancer-related fatigue (CRF) is still undertreated in most patients, as evidence for pharmacological treatments is limited and conflicting. Also, the efficacy of the pharmacological agents relative to each other is still unclear. Therefore, medications that may potentially contribute to improving CRF will be investigated in this head-to-head trial. Our main objective is to compare the efficacy of methylphenidate vs. bupropion vs. ginseng vs. amantadine vs. placebo in patients with advanced cancer. The 5-EPIFAT study is a 5-arm, randomized, multi-blind, placebo-controlled, multicenter trial that will use a parallel-group design with an equal allocation ratio comparing the efficacy and safety of four medications (Methylphenidate vs. Bupropion vs. Ginseng vs. Amantadine) versus placebo for management of CRF. We will recruit 255 adult patients with advanced cancer who experience fatigue intensity ≥ 4 based on a 0–10 scale. The study period includes a 4-week intervention and a 4-week follow-up with repeated measurements over time. The primary outcome is the cancer-related fatigue level over time, which will be measured by the functional assessment of chronic illness therapy-fatigue (FACIT-F) scale. To evaluate safety, the secondary outcome is the symptomatic adverse events, which will be assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events in cancer clinical trials (PRO-CTCAE). Also, a subgroup analysis based on a decision tree-based machine learning algorithm will be employed for the clinical prediction of different agents in homogeneous subgroups. The findings of the 5-EPIFAT trial could be helpful to guide clinical decision-making, personalization treatment approach, design of future trials, as well as the development of CRF management guidelines. IRCT.ir IRCT20150302021307N6. Registered on 13 May 2023.

中文翻译：

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5-EPIFAT 试验方案：一项多中心、随机、安慰剂对照试验，研究使用哌醋甲酯、安非他酮、人参和金刚烷胺对接受积极治疗的晚期癌症患者进行药物治疗疲劳的疗效

由于药物治疗的证据有限且相互矛盾，大多数患者的癌症相关性疲劳（CRF）仍未得到充分治疗。此外，药物之间相对的功效仍不清楚。因此，本次头对头试验将研究可能有助于改善 CRF 的药物。我们的主要目的是比较哌醋甲酯、安非他酮、人参、金刚烷胺、安慰剂对晚期癌症患者的疗效。 5-EPIFAT 研究是一项 5 臂、随机、多盲、安慰剂对照、多中心试验，将使用具有相等分配比例的平行组设计，比较四种药物（哌醋甲酯、安非他酮、安非他酮）的疗效和安全性。 . 人参与金刚烷胺）与安慰剂治疗 CRF 的比较。我们将招募 255 名患有晚期癌症的成年患者，他们的疲劳强度基于 0-10 等级≥ 4。研究期包括 4 周的干预和 4 周的随访，并随时间的推移进行重复测量。主要结果是随着时间的推移与癌症相关的疲劳水平，这将通过慢性病治疗疲劳（FACIT-F）量表的功能评估来测量。为了评估安全性，次要结果是有症状的不良事件，将使用癌症临床试验中不良事件通用术语标准 (PRO-CTCAE) 的患者报告结果版本进行评估。此外，基于决策树的机器学习算法的亚组分析将用于同质亚组中不同药物的临床预测。 5-EPIFAT试验的结果可能有助于指导临床决策、个性化治疗方法、未来试验的设计以及CRF管理指南的制定。 IRCT.ir IRCT20150302021307N6。注册日期：2023 年 5 月 13 日。