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.
研究组 & 干预措施
Nurse-Led Treatment in Primary Care
At a primary care clinic intervention site, a nurse will be available once or twice weekly. The days/times will be dependent on clinic volume (i.e., cluster size), with scheduled rotations between PCCs. This rotation between PCC sites will mimic the physician's responsibilities/availability at a district hospital and creates parity between the trial arms. In this trial, we will have nurses dedicated to the management of RR-TB treatment, yet the volume at each site will not require the presence of a full-time nurse.
干预措施: Nurse-Led Treatment in Primary Care (Other)
Physician-Led Treatment Hospital Based
Representing standard of care, primary care clinics will refer to hospital-based, physician-led care who will provide outpatient treatment. The typical clinical operations involve initiation of new patients once or twice weekly and PCCs are required to schedule a clinic day/time for the patient prior to referral (generally < 72 hours from the time of referral). All individuals receiving care at this site will receive care at the district RR-TB treatment program for the catchment area. For HIV co-infected persons, their HIV treatment is also transferred to the RR-TB physician with details about the HIV treatment communicated in the transfer of care letter. Physicians often cover multiple clinics and routinely take on call sessions on the weekend, due to staffing limitations, thus preventing their sole focus on the RR-TB program and limiting the number of days the RR-TB clinic offers new patient visits and, in most cases, days for follow-up visits.
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)