bring bpal2me trial comparing nurse-led rr-tb treatment to physician-led rr-tb treatment

Conditions: Drug Resistant Tuberculosis

Summary: 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: 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 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 \[h3\].

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: 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.

Eligibility criteria:
inclusion criteria: cluster inclusion criteria: primary care clinics (pccs) (i.e., clusters) are eligible if they meet the following: 1. within one of the selected hospital treatment catchment areas in kwazulu-natal, gauteng and eastern cape provinces; 2. willingness of provincial tb program managers and hospital leadership to participate; 3. willingness of pcc nurse manager to participate; 4. diagnosis of 10 or more rr-tb patients per year; and 5. 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 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); 2. hemoglobin \ 120 u/l); 3. prolonged qtc\>470ms, confirmed by 2 or more ecg; 4. rapid heartrate, tachycardia (hr \>140); confirmed after 5 minutes of rest; 5. pregnancy; 6. evidence of extrapulmonary disease; 7. enrolled in another clinical trial that changes bpal-l regimen, duration or symptom management process.

Keywords: nurse-led non-inferiority cluster randomized trial primary care drug resistant tuberculosis rifampicin resistant tuberculosis human immunodeficiency virus task sharing south africa