The Bring BPaL2Me Trial - Comparing Nurse-Led RR-TB Treatment in Primary Care to Physician-Led, Hospital-Based RR-TB Treatment: A Cluster Randomized, Non-Inferiority Trial

在南非(SA)，结核分枝杆菌(TB)由初级保健诊所(PCCs)管理，在那里 护士治疗药物敏感的结核病和结核病/艾滋病毒合并感染，其治疗结果堪比世界上最好的。 PCC管理策略提供了更方便、以患者为中心的差异化护理模式， 将结核病和艾滋病毒的治疗纳入同一环境。利福平耐药结核病(RR-TB)诊断， 然而，它颠覆了这种模式，需要转诊到以医院为基础、由医生领导的门诊治疗中心。 以医院为基础、由医生主导的模型增加了显著的患者相关成本，估计表明81%的 即使在分散的门诊模式中，RR-TB患者也会经历灾难性的成本。然而，还是有希望的， 为了将RR-TB护理转移到初级保健中心，在许多情况下，这涉及到护士领导的管理。The BringBPaL2Me 试验是一项多主体、多地点、整群随机、非劣势试验(CR-NIT)，以进行比较 年，在PCC中由护士领导的RR-TB治疗达到了标准护理由医生领导的RR-TB治疗 夸祖鲁-纳塔尔省(KZN)、豪登省(GP)和东开普省(EC)、南非。集群包括10个PCC 隶属于5个分散在RR-TB地区医院的门诊项目(n=50个集群)。我们估计 需要对3,800名RR-TB阳性患者进行筛查，才能在每个PCC组招募2,944名或RR-TB参与者。我们 估计有60%-70%的人会同时感染艾滋病毒。基于我们之前的CRT注册，类间相关性为0.024 KZN和EC的3000名患者。非劣势边际设定为5%，假设为90%的治疗 在医生引导的手臂上取得成功。治疗将包括为期6个月的RR-TB方案(即，贝达奎兰， 耐氟喹诺酮结核(即BPaL)方案。这个 BringBPaL2Me的主要目标是进行为期5年的分析师和临床安全审查委员会盲目、多 现场，CR-NIT评估1)治疗结果；2)安全性；3)患者与 以下假设：1)门诊护士主导的PCCS治疗将不逊于门诊医生主导的治疗 在以医院为基础的门诊地点治疗RR-TB患者，无论是否合并艾滋病毒感染，AS 由成功的治疗结果确定[h1]；2)确定的严重不良事件(SAE)的比例 不会因盲目的独立审查而有显著差异[H2]；3)与患者相关的灾难性成本(即， 费用占家庭收入的20%或更多)在护士引导的治疗中将会更低[H3]。我们的次要目标包括： 1)事件发生时间分析：a)RR-TB治疗启动；b)涂片/培养转换；以及，如适用，c) 艾滋病毒治疗启动；d)艾滋病毒病毒抑制；和e)AE和SAE症状的解决；2)特征 提供商遵守以下准则的情况：a)剂量要求；b)基于AE和SAE的RR-TB剂量变化 事件；以及c)AE和SAE辅助用药管理战略；3)方案成本效益 对PCC管理的评价。带来BPaL2Me拥有强大的多PI协作，得到了 国家/省卫生厅团队和严格的设计，以评估有效性、安全性和成本。

In South Africa (SA), Mycobacterium tuberculosis (TB) is managed within primary care clinics (PCCs), where nurses treat drug-susceptible TB and TB/HIV coinfection with treatment outcomes rivaling the best in the world. A PCC management strategy offers a more convenient, patient-centered, differentiated model of care that integrates TB and HIV treatment within the same setting. A diagnosis of rifampicin-resistant TB (RR-TB), however, upends this model, requiring referral to a hospital-based, physician-led outpatient treatment center. Hospital-based, physician-led models add significant patient-associated costs, with estimates suggesting 81% of RR-TB patients experience catastrophic costs even in a decentralized outpatient model. There is hope, however, to move RR-TB care into PCCs and in many settings this involves nurse-led management. The BringBPaL2Me Trial is a multi-principal investigator, multi-site, cluster randomized, non-inferiority trial (CR-NIT), to compare nurse-led RR-TB treatment in PCCs to standard of care physician-led RR-TB treatment at district hospitals in the provinces of KwaZulu-Natal (KZN), Gauteng (GP) and Eastern Cape (EC), SA. Clusters include 10 PCCs affiliated with 5 decentralized outpatient programs at RR-TB district hospitals (n=50 clusters). We estimate the need to screen 3,800 RR-TB positive patients to enroll 2,944, or 64 RR-TB participants per PCC cluster. We estimate 60-70% will be HIV co-infected. The interclass correlation is 0.024 based on our prior CRT enrolling 3,000 patients in KZN and EC. The non-inferiority margin is set at 5% with the assumption of 90% treatment success in the physician-led arm. Treatment will include either a 6-month RR-TB regimen (i.e., bedaquiline, pretomanid, linezolid and moxifloxacin, or BPaLM) or fluroquinolone-resistant TB (i.e., BPaL) regimen. The BringBPaL2Me primary aim is to conduct a 5-year, analyst and clinical safety review committee blinded, multi- site, CR-NIT to evaluate 1) treatment outcome; 2) safety; and 3) patient associated catastrophic costs with the following hypotheses: 1) Outpatient nurse-led treatment in PCCs will be non-inferior to outpatient physician-led treatment at hospital-based outpatient sites among RR-TB patients, regardless of HIV co-infection, as determined by a successful treatment outcome [H1]; 2) The proportion of severe adverse events (SAEs) identified will not significantly differ by blinded, independent review [H2]; 3) Patient associated catastrophic costs (i.e., costs 20% or more of household income) will be lower in nurse-led treatment [H3]. Our secondary aims include: 1) time to event analysis for a) RR-TB treatment initiation; b) smear/culture conversion; and, as applicable, c) HIV treatment initiation; d) HIV viral suppression; and e) AE and SAE symptom resolution; 2) characterization of provider adherence to guidelines for: a) dosing requirements; b) RR-TB dosing changes based on AE and SAE events; and c) AE and SAE adjuvant medication management strategy; 3) programmatic cost-effectiveness evaluation of PCC management. Bring BPaL2Me has strong multi-PI collaborations with support from the national/provincial department of health teams and a rigorous design to evaluate effectiveness, safety and costs.