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) 内进行管理，其中 护士治疗药物敏感结核病和结核病/艾滋病毒合并感染的治疗效果可与世界上最好的治疗效果相媲美。 PCC 管理策略提供了一种更方便、以患者为中心、差异化的护理模式， 将结核病和艾滋病毒治疗整合到同一环境中。利福平耐药结核病 (RR-TB) 的诊断， 然而，它颠覆了这种模式，需要转诊到以医院为基础、医生主导的门诊治疗中心。 以医院为基础、医生主导的模型显着增加了患者相关成本，估计表明 81% 即使在分散的门诊模式中，RR-TB 患者也会经历灾难性的费用。不过，还有希望， 将 RR-TB 护理转移到 PCC，在许多情况下，这涉及护士主导的管理。带来 BPaL2Me 试验是一项多主要研究者、多中心、整群随机、非劣效性试验 (CR-NIT)，以比较 PCC 中由护士主导的 RR-TB 治疗达到地区医院由医生主导的 RR-TB 治疗的护理标准 夸祖鲁-纳塔尔省 (KZN)、豪登省 (GP) 和东开普省 (EC)、南澳州。集群包括 10 个 PCC 隶属于 RR-TB 地区医院的 5 个分散门诊项目（n = 50 个集群）。我们估计 需要筛查 3,800 名 RR-TB 阳性患者，才能在每个 PCC 集群中招募 2,944 名或 64 名 RR-TB 参与者。我们 估计 60-70% 将同时感染 HIV。根据我们之前的 CRT 注册，类间相关性为 0.024 KZN 和 EC 的 3,000 名患者。假设治疗率为 90%，非劣效裕度设定为 5% 在医生主导下取得成功。治疗将包括为期 6 个月的 RR-TB 治疗方案（即贝达喹啉、 普托马尼、利奈唑胺和莫西沙星，或 BPaLM）或氟喹诺酮耐药结核病（即 BPaL）治疗方案。这 BringBPaL2Me 的主要目标是开展为期 5 年的分析师和临床安全审查委员会的盲法、多方评估 地点，CR-NIT 评估 1) 治疗结果； 2）安全； 3) 与患者相关的灾难性费用 以下假设：1) PCC 中门诊护士主导的治疗将不劣于门诊医生主导的治疗 RR-TB 患者在医院门诊接受治疗，无论是否同时感染 HIV， 由成功的治疗结果决定[H1]； 2) 已确定的严重不良事件 (SAE) 的比例 通过盲法、独立审查不会有显着差异[H2]； 3) 与患者相关的灾难性费用（即， 护士主导的治疗费用（占家庭收入的 20% 或更多）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 治疗开始； b) 涂片/培养转换；以及，如适用，c) 开始艾滋病毒治疗； d) HIV 病毒抑制； e) AE 和 SAE 症状缓解； 2）表征 提供者遵守以下准则： a) 剂量要求； b) 根据 AE 和 SAE 改变 RR-TB 剂量 事件； c) AE 和 SAE 辅助用药管理策略； 3）程序化成本效益 PCC管理评价。 Bring BPaL2Me 在以下机构的支持下拥有强大的多 PI 合作 国家/省卫生部门团队和严格的设计来评估有效性、安全性和成本。