Overview
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].
Description
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 physicianand 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.
Eligibility
Inclusion Criteria:
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 15 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 Exclusion Criteria:
1. any clinical presentation requiring hospital referral (e.g., severe weakness,
confusion, severe mental illness);
2. laboratory or clinical evidence of myelosuppression (hemoglobin < 8mg/dL; absolute
neutrophil count <1800/microL; platelet count < 150,000/microL), renal (eGFR<60mL/min)
or liver disease (ALT > 2 times upper limit of normal);
3. prolonged QTc>500ms;
4. pregnancy;
5. evidence of extrapulmonary disease;
6. any condition (social or medical), which in the opinion of the investigators, would
make participation unsafe.