Bring BPaL2Me Trial Comparing Nurse-Led RR-TB Treatment in Primary Care to Physician-Led, Hospital-Based Outpatient RR-TB Treatment: A Cluster Randomized, Non-Inferiority Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 2,944
- 试验地点
- 9
- 主要终点
- RR-TB treatment outcome
研究概览
简要总结
The goal of the BringBPaL2Me Trial, a multi-principal investigator, multi-site, cluster randomized, non-inferiority trial is to compare nurse-led RR-TB treatment in primary care clinics to standard of care physician-led RR-TB treatment at district hospitals in the provinces of KwaZulu-Natal, Gauteng, and Eastern Cape.
The main aim is to conduct a 5-year, analyst and clinical safety review committee blinded, multi-site, cluster randomized trial to evaluate 1) treatment outcome; 2) safety; 3) patient associated catastrophic costs with the following hypotheses:
- 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].
- The proportion of SAEs identified will not significantly differ by blinded, independent review [H2].
- Patient associated catastrophic costs (i.e., costs 20% or more of household income) will be lower in nurse-led treatment [H3].
详细描述
In South Africa (SA), nurses manage drug-susceptible Mycobacterium tuberculosis (TB) and TB/HIV coinfection within primary care clinics (PCCs); the TB treatment outcomes in this care model rival the best in the world. A primary care management strategy offers a convenient, patient-centered, model of care that integrates TB and HIV treatment within the same setting. However, a diagnosis of rifampicin-resistant TB (RR-TB), upends this model, requiring referral to a hospital-based, physician-led outpatient treatment center.
Hospital-based models add significant costs to patients, with estimates suggesting more than 80% of RR-TB patients experience catastrophic costs. Such added costs may decrease access to care, delay treatment receipt and contribute to loss to follow-up. One testable solution to this problem, however, is to move RR-TB care to primary care clinics led by nurses. The World Health Organization (WHO) released recommendations for RR-TB treatment earlier this year endorsing 6-month regimens and calling for decentralized, patient-centered models of care closer to the patient's home.
Although SA has long been a leading implementer of nurse-led models of care for TB and HIV due to large physician shortages and the National Department of Health's (NDoH) RR-TB Treatment Guidelines recommend integration of RR-TB within PCCs supporting both physician- and nurse-led models, utilization has been limited. While the team has spent the last decade building observational evidence around outcomes and safety, no randomized controlled trial evaluates nurse-led RR-TB treatment.
Secondary Aims: To evaluate clinical and cost-associated differentiators by arm:
- 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.
- 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.
- Programmatic cost-effectiveness evaluation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Health Services Research
- 盲法
- Double (Investigator, Outcomes Assessor)
盲法说明
We will mask the investigators, statistician and safety review committee to treatment assignment.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cluster Inclusion Criteria:
- •Primary Care Clinics (PCCs) (i.e., clusters) are eligible if they meet the following:
- •within one of the selected hospital treatment catchment areas in Kwazulu-Natal, Gauteng and Eastern Cape Provinces;
- •willingness of provincial TB program managers and hospital leadership to participate;
- •willingness of PCC nurse manager to participate;
- •diagnosis of 10 or more RR-TB patients per year; and
- •have access to necessary labs, X-ray and electrocardiogram (ECG) equipment.
- •Participant Inclusion Criteria:
- •Adult participants aged 18 years of age and older, regardless of HIV status, who have a new RR-TB diagnosis, deemed willing and able to provide informed consent in one of the four most common SA languages [Zulu, Xhosa, Afrikaans, and English] will be eligible.
- •Participant
排除标准
- •any clinical presentation requiring hospital admission or, in other words, the participant is not a candidate for outpatient primary care initiation (e.g., severe weakness, confusion, severe mental illness, symptomatic low blood pressure, severe shortness of breath, and temp >39.0);
- •Hemoglobin < 8mg/dL (from National Health Laboratory Service (NHLS) or point of care)) or liver disease (ALT > 120 U/L);
- •prolonged QTc>470ms, confirmed by 2 or more ecg;
- •rapid heartrate, tachycardia (HR >140); confirmed after 5 minutes of rest;
- •evidence of extrapulmonary disease;
- •enrolled in another clinical trial that changes BPaL-L regimen, duration or symptom management process.
结局指标
主要结局
RR-TB treatment outcome
时间窗: 6 months
defined by the WHO will include the following: treatment success - the sum of cure and treatment completion; non-success - composite of each of the following negative outcomes: death, for any reason, while enrolled in RR-TB treatment (all-cause mortality); treatment failure - treatment terminated or need for permanent regimen change of at least two drugs because of: lack of culture conversion, bacterial reversion, worsening resistance profile, adverse events; and loss to follow-up interruption of 2 or more consecutive months of missed treatment.
Severe Adverse Events as assessed by the Division of AIDS (DAIDS) AE grading table
时间窗: 12 months
The following will be classified as an SAE using the DAIDS AE grading table for the purposes of this protocol: 1. Lab abnormalities demonstrating grade 3 or higher: Myelosuppression (White blood cells (WBC), Red blood cells (RBC), Platelets); hepatotoxicity (Alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin); renal impairment (serum creatinine and creatinine clearance) 2. Peripheral neuropathy, grade 3 or higher 3. QT prolongation (Frederica's QTc), grade 3 or higher 4. New onset seizure, regardless of grade 5. Hospitalization, regardless of identified cause 6. Mortality, regardless of identified cause 7. All grade 4 AEs not listed above as an SAE
Patient associated catastrophic costs
时间窗: 12 months
(Costs 20% or more of household income) will be lower in nurse-led treatment
次要结局
- Time to RR-TB treatment initiation(60 days from trial screening)
- Time to smear/culture conversion(120 days after treatment initiation)
- Time to HIV treatment initiation(120 days after treatment initiation)
- Time to HIV viral suppression(6 months)
- RR-TB dosing changes based on AE and SAE events(12 months)
- Time to adverse (AE) and severe (SAE) treatment related adverse event resolution(12 months)
- Time to initiation of HIV prevention(6 months)
- Provider adherence to dosing requirements, treatment initiation(1 month)
- AE and SAE adjuvant medication management strategy(12 months)
- Programmatic cost effectiveness evaluation(12 months)