Supplementary Material for: CONKO-011/AIO-SUP-0115/ass.: Rivaroxaban compared to Low Molecular Weight Heparin in Cancer Patients with Acute Venous Thromboembolism

Introduction Cancer-associated venous thromboembolism (CAT) is a frequent and medical relevant problem. Guidelines recommend treatment with low molecular weight heparins (LMWH) or direct oral factor-Xa-inhibitors as rivaroxaban for > 3 months. Patient’s preference and convenience is an important factor to guide treatment decision and to support treatment adherence. No data are available so far about patient-reported outcome in CAT. Methods CONKO-011 was an open-label, prospective, multicenter German phase III trial for cancer patients with newly diagnosed venous thromboembolism (VTE) randomized to rivaroxaban (Riva) or site-specific LMWH. Primary endpoint was patient-reported treatment satisfaction, measured by the Anti-Clot Treatment Scale (ACTS). The 12-item ACTS Burdens scale (primary endpoint after 4 weeks) and the 3-item ACTS Benefits scale were analyzed at 4, 8 and 12 weeks. Secondary endpoints included recurrent VTE, major/ clinically relevant bleeding, safety, compliance, overall mortality at 3 and 6 months, Quality of life (QOL) measured by the Treatment Satisfaction Questionnaire for Medication II (TSQM II) and Spitzer Index. Results Between 03/2016 and 06/2019, 247 (123 Riva/124 LMWH) patients were randomized. Mean ACTS Burdens scores after 4 weeks were 52.8 versus 51.2 in favor of rivaroxaban (p = 0.019) with mean score differences ranging from 3.3 (week 8; p = 0.001) to 2.4 (week 12; p = 0.006). The treatment effect of ACTS burden was consistent over treatment time (p < 0.001). More patients on LMWH requested to stop study treatment preterm (19.4% versus 11.1%). Conclusion Oral treatment with rivaroxaban led to an improvement in patient-reported treatment satisfaction, particularly in reducing anticoagulation-related burden, resulting in less patient-requested treatment stops.

### 引言
癌症相关静脉血栓栓塞症（Cancer-associated venous thromboembolism, CAT）是一类常见且具有临床意义的医学问题。临床指南推荐采用低分子肝素（low molecular weight heparins, LMWH）或直接口服Xa因子抑制剂（如利伐沙班）进行为期3个月以上的治疗。患者的治疗偏好与便利性是指导治疗决策、提升治疗依从性的关键因素，目前尚无针对癌症相关静脉血栓栓塞症患者报告结局的公开数据。

### 方法
CONKO-011是一项开放标签、前瞻性、多中心的德国III期临床试验，针对新诊断静脉血栓栓塞症（venous thromboembolism, VTE）的癌症患者，将其随机分配至利伐沙班（Riva）组或机构指定低分子肝素组。本试验的主要终点为患者报告的治疗满意度，采用抗凝血治疗量表（Anti-Clot Treatment Scale, ACTS）进行评估。其中12条目ACTS负担量表（第4周为主要评估时点）与3条目ACTS获益量表，分别在第4、8、12周进行数据分析。次要终点包括复发性静脉血栓栓塞症、大出血/临床相关性出血、治疗安全性、依从性、3个月与6个月时的总死亡率，以及采用药物治疗满意度调查问卷II（Treatment Satisfaction Questionnaire for Medication II, TSQM II）与斯皮策指数（Spitzer Index）评估的生活质量（Quality of Life, QOL）。

### 结果
2016年3月至2019年6月期间，共纳入247例符合条件的患者（利伐沙班组123例，低分子肝素组124例）并完成随机分组。第4周时，利伐沙班组的ACTS负担量表平均得分为52.8，低分子肝素组为51.2，利伐沙班组表现更优（p=0.019）；两组平均得分差范围为3.3（第8周，p=0.001）至2.4（第12周，p=0.006）。ACTS负担的治疗效应随治疗时长保持稳定（p<0.001）。低分子肝素组中主动请求提前终止研究治疗的患者比例更高（19.4% vs 11.1%）。

### 结论
口服利伐沙班治疗可显著提升患者报告的治疗满意度，尤其在降低抗凝相关治疗负担方面效果突出，从而减少患者主动请求提前终止治疗的比例。