Bring BPaL2Me Trial Comparing Nurse-Led RR-TB Treatment to Physician-Led RR-TB Treatment
- Conditions
- Drug Resistant Tuberculosis
- Interventions
- Other: Nurse-Led Treatment in Primary Care
- Registration Number
- NCT05671718
- Lead Sponsor
- Johns Hopkins University
- Brief 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 \[H3\].
- Detailed 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 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 2944
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
- 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;
- pregnancy;
- evidence of extrapulmonary disease;
- enrolled in another clinical trial that changes BPaL-L regimen, duration or symptom management process.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Nurse-Led Treatment in Primary Care 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.
- Primary Outcome Measures
Name Time Method Patient associated catastrophic costs 12 months (Costs 20% or more of household income) will be lower in nurse-led treatment
RR-TB treatment outcome 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 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
- Secondary Outcome Measures
Name Time Method Time to RR-TB treatment initiation 60 days from trial screening Time to event analysis between diagnosis and treatment initiation
Time to smear/culture conversion 120 days after treatment initiation Time to event analysis between treatment initiation and smear and culture conversion
Time to HIV treatment initiation 120 days after treatment initiation Time to event analysis between enrollment and Antiretroviral therapy (ART) initiation
Time to HIV viral suppression 6 months Time to event analysis between enrollment and HIV viral load \< 200 copies
RR-TB dosing changes based on AE and SAE events 12 months Provider appropriately manages RR-TB regimen based on AE and SAE events, as determined by blinded safety review
Time to adverse (AE) and severe (SAE) treatment related adverse event resolution 12 months Time to event analysis for adverse and severe treatment related adverse events
Time to initiation of HIV prevention 6 months Time to event analysis between enrollment and HIV prevention initiation for HIV negative patients
Provider adherence to dosing requirements, treatment initiation 1 month Accuracy of regimen dosing based on treatment guidelines
AE and SAE adjuvant medication management strategy 12 months Provider appropriately manages AE and SAE events, as determined by blinded safety review
Programmatic cost effectiveness evaluation 12 months For the health system costs, we will use standard approaches outlined in "Value TB" costing guidelines for TB interventions. If the costs averted are found to be greater than the cost of the nurse-led PCC so that intervention saves money and is non-inferior, then it can be described as dominating (a more effective, less expensive choice) and it is economically the correct choice. In contrast, if the nurse-led PCC is non-inferior and yet more expensive, then we will calculate an incremental cost-effectiveness ratio (i.e., (CostNurse-CostUsual care)/(EffectNurse-EffectUsualCare)) that describes the extra costs necessary for each additional cured case.
Trial Locations
- Locations (5)
Doris Goodwin Hospital
🇿🇦Pietermaritzburg, KwaZulu-Natal, South Africa
Murchison Hospital
🇿🇦Port Shepstone, KwaZulu-Natal, South Africa
King Dinuzulu TB Hospital
🇿🇦East London, South Africa
Nkquebela TB Hospital
🇿🇦East London, South Africa
Jose Pearson Hospital
🇿🇦Port Elizabeth, South Africa