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

Bring BPaL2Me 试验 - 比较初级保健中护士主导的 RR-TB 治疗与医生主导、医院为基础的 RR-TB 治疗：整群随机、非劣效性试验

• 批准号: 10698492
• 负责人: Denise Evans
• 金额: $ 80.01万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-10 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10698492
• 关键词: Adherence; Adjuvant Analgesic; Ambulatory Care; Antibiotic Resistance; Blinded; Caring; Clinical; Clinical Trials Data Monitoring Committees; Collaborations; Communicable Diseases; Decentralization; Diagnosis; District Hospitals; Dose; Early treatment; Education; Enrollment; Event; Guidelines; HIV; HIV/TB; Health; Health Services Accessibility; Health system; Home; Hospitals; Household; Improve Access; Income; Infection; Linezolid; Managed Care; Medication Management; Modeling; Moxifloxacin; Mycobacterium tuberculosis; Nurses; Oral; Outcome; Outpatients; Participant; Patients; Persons; Pharmaceutical Preparations; Physicians; Predisposition; Primary Care; Principal Investigator; Province; Public Health; Randomized; Randomized, Controlled Trials; Recommendation; Regimen; Reporting; Research; Resistance; Resolution; Review Committee; Rifampicin resistance; Safety; Serious Adverse Event; Site; South Africa; South African; Standardization; Symptoms; Testing; Time; Treatment Protocols; Treatment outcome; Tuberculosis; Viral; World Health Organization; arm; chronic care model; co-infection; cost; cost-effectiveness evaluation; design; effectiveness evaluation; experience; fluoroquinolone resistance; follow-up; improved; outpatient programs; patient oriented; primary care clinic; programs; provider adherence; standard of care; success; treatment center; treatment guidelines; trial comparing; tuberculosis treatment

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.

在南非（SA），结核分枝杆菌（TB）在初级保健诊所（PCC）中进行管理 护士通过与世界上最好的治疗结果相媲美的治疗结果来治疗可敏感的结核病和结核病/艾滋病毒感染。 PCC管理策略提供了一种更方便，以患者为中心的，差异化的护理模型， 在同一环境中整合结核病和艾滋病毒治疗。利福平耐药TB（RR-TB）的诊断， 但是，这一模型需要转介给以医院为基础的医师为主导的门诊治疗中心。 以医院为基础的医师指导的模型增加了与患者相关的大量成本，估计表明81％ RR-TB患者即使在分散的门诊模型中也经历了灾难性的成本。但是，有希望 为了将RR-TB护理转移到PCC中，在许多情况下，这涉及护士主导的管理。 bringbpal2me 试验是一项多首席研究员，多站点，群集随机，非效率试验（CR-NIT），用于比较 PCC中由护士领导的RR-TB治疗，用于护理医师主导的RR-TB治疗 豪登省（KZN），豪登省（GP）和东开普省（EC）的省。集群包括10个PCC 在RR-TB地区医院（n = 50个集群）隶属于5个分散的门诊计划。我们估计 需要筛选3,800名RR-TB阳性患者以招募2,944个，或每个PCC群集64例RR-TB参与者。我们 估计为60-70％的HIV共感染。基于我们先前的CRT注册，类间相关性为0.024 KZN和EC的3,000名患者。假设治疗90％ 以医师为主导的手臂成功。治疗将包括6个月的RR-TB方案（即Bedaquiline， Pitmanid，lineZolid和Moxifloxacin，或BPALM）或抗氟喹诺酮耐药性结核病（即BPAL）方案。这 BringbPal2Me的主要目的是进行5年，分析师和临床安全审查委员会盲目，多重 地点，CR-NIT评估1）治疗结果； 2）安全； 3）患者与患者相关的灾难性成本与 以下假设：1）在PCC中以门诊护士为主导的治疗将不在门诊医师领导的情况下 无论艾滋病毒共同感染如何 由成功的治疗结果[H1]决定； 2）确定的严重不良事件（SAE）的比例 盲目的独立审查不会显着差异[H2]； 3）患者相关的灾难性成本（即 在护士主导的治疗中，成本为20％或以上的家庭收入将较低[H3]。我们的次要目标包括： 1）a）RR-TB治疗启动的事件分析时间； b）涂片/文化转换；而且，如适用，c） HIV治疗开始； D）HIV病毒抑制； E）AE和SAE症状解决； 2）表征 提供者遵守指南：a）给药要求； b）基于AE和SAE的RR-TB给药更改 事件； c）AE和SAE辅助药物管理策略； 3）程序化的成本效益 PCC管理评估。 Bring BPAL2Me在支持的情况下进行了强大的多PI合作 国家/省级卫生团队和严格的设计，以评估有效性，安全性和成本。