Bring BPaL2Me Trial Comparing Nurse-Led RR-TB Treatment to Physician-Led RR-TB Treatment

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].

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; andhave 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:BMI < 18 kg/m2;any clinical presentation requiring hospital referral (e.g., severe weakness, confusion, severe mental illness);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);prolonged QTc>500ms;pregnancy;evidence of extrapulmonary disease;unconfirmed RR-TB (e.g., discordant diagnostic results);history of prior treatment for RR-TB with this regimen (i.e., retreatment case).