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 \[H3\].
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
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;
Parallel
Nurse-Led Treatment in Primary Care
Other interventionAt 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.
RR-TB treatment outcome
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
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
(Costs 20% or more of household income) will be lower in nurse-led treatment
Time to RR-TB treatment initiation
Time to event analysis between diagnosis and treatment initiation
Time to smear/culture conversion
Time to event analysis between treatment initiation and smear and culture conversion
Time to HIV treatment initiation
Time to event analysis between enrollment and Antiretroviral therapy (ART) initiation
Time to HIV viral suppression
Time to event analysis between enrollment and HIV viral load \< 200 copies
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Johns Hopkins University
Lead sponsor
University of Witwatersrand, South Africa
Collaborator
University of Cape Town
Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator
