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

NCT05671718 | Recruiting DMC

• 2 other identifiers: IRB00234475R01AI177135-01
• Study Type: interventional
• Target: 2,944
• Locations: 1 country
• Sites: 5

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. 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. 2.The proportion of SAEs identified will not significantly differ by blinded, independent review \[H2\].
3. 3.Patient associated catastrophic costs (i.e., costs 20% or more of household income) will be lower in nurse-led treatment \[H3\].

Conditions

Drug Resistant Tuberculosis

Keywords

nurse-led; non-inferiority cluster randomized trial; primary care; drug resistant tuberculosis; rifampicin resistant tuberculosis; human immunodeficiency virus; task sharing; South Africa

Outcome Measures

Primary Outcomes (3)

• 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.

  6 months

• 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

  12 months

• Patient associated catastrophic costs

  (Costs 20% or more of household income) will be lower in nurse-led treatment

  12 months

Secondary Outcomes (10)

• Time to RR-TB treatment initiation

  60 days from trial screening

• Time to smear/culture conversion

  120 days after treatment initiation

• Time to HIV treatment initiation

  120 days after treatment initiation

• Time to HIV viral suppression

  6 months

• RR-TB dosing changes based on AE and SAE events

  12 months

Study Arms (2)

Nurse-Led Treatment in Primary Care

EXPERIMENTAL

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.

Other: Nurse-Led Treatment in Primary Care

Physician-Led Treatment Hospital Based

NO INTERVENTION

Representing standard of care, primary care clinics will refer to hospital-based, physician-led care who will provide outpatient treatment. The typical clinical operations involve initiation of new patients once or twice weekly and PCCs are required to schedule a clinic day/time for the patient prior to referral (generally \< 72 hours from the time of referral). All individuals receiving care at this site will receive care at the district RR-TB treatment program for the catchment area. For HIV co-infected persons, their HIV treatment is also transferred to the RR-TB physician with details about the HIV treatment communicated in the transfer of care letter. Physicians often cover multiple clinics and routinely take on call sessions on the weekend, due to staffing limitations, thus preventing their sole focus on the RR-TB program and limiting the number of days the RR-TB clinic offers new patient visits and, in most cases, days for follow-up visits.

Interventions

Nurse-Led Treatment in Primary Care OTHER

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.

Nurse-Led Treatment in Primary Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Johns Hopkins University: lead
• University of Witwatersrand, South Africa: collaborator
• University of Cape Town: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (5)

Doris Goodwin Hospital

Pietermaritzburg, KwaZulu-Natal, 3201, South Africa

RECRUITING

Murchison Hospital

Port Shepstone, KwaZulu-Natal, 7007, South Africa

RECRUITING

King Dinuzulu TB Hospital

East London, South Africa

RECRUITING

Nkquebela TB Hospital

East London, South Africa

RECRUITING

Jose Pearson Hospital

Port Elizabeth, South Africa

RECRUITING

Related Publications (6)

• van Rensburg C, Berhanu R, Hirasen K, Evans D, Rosen S, Long L. Cost outcome analysis of decentralized care for drug-resistant tuberculosis in Johannesburg, South Africa. PLoS One. 2019 Jun 6;14(6):e0217820. doi: 10.1371/journal.pone.0217820. eCollection 2019.

  PMID: 31170207 BACKGROUND

• Laurence YV, Griffiths UK, Vassall A. Costs to Health Services and the Patient of Treating Tuberculosis: A Systematic Literature Review. Pharmacoeconomics. 2015 Sep;33(9):939-55. doi: 10.1007/s40273-015-0279-6.

  PMID: 25939501 BACKGROUND

• Ho J, Byrne AL, Linh NN, Jaramillo E, Fox GJ. Decentralized care for multidrug-resistant tuberculosis: a systematic review and meta-analysis. Bull World Health Organ. 2017 Aug 1;95(8):584-593. doi: 10.2471/BLT.17.193375.

  PMID: 28804170 BACKGROUND

• Masuku SD, Berhanu R, Van Rensburg C, Ndjeka N, Rosen S, Long L, Evans D, Nichols BE. Managing multidrug-resistant tuberculosis in South Africa: a budget impact analysis. Int J Tuberc Lung Dis. 2020 Apr 1;24(4):376-382. doi: 10.5588/ijtld.19.0409.

  PMID: 32317060 BACKGROUND

• Crowley T, Mokoka E, Geyer N. Ten years of nurse-initiated antiretroviral treatment in South Africa: A narrative review of enablers and barriers. South Afr J HIV Med. 2021 Mar 11;22(1):1196. doi: 10.4102/sajhivmed.v22i1.1196. eCollection 2021.

  PMID: 33824736 BACKGROUND

• Uebel KE, Fairall LR, van Rensburg DH, Mollentze WF, Bachmann MO, Lewin S, Zwarenstein M, Colvin CJ, Georgeu D, Mayers P, Faris GM, Lombard C, Bateman ED. Task shifting and integration of HIV care into primary care in South Africa: the development and content of the streamlining tasks and roles to expand treatment and care for HIV (STRETCH) intervention. Implement Sci. 2011 Aug 2;6:86. doi: 10.1186/1748-5908-6-86.

  PMID: 21810242 BACKGROUND

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant; Acquired Immunodeficiency Syndrome

Interventions

Primary Health Care

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Comprehensive Health Care; Patient Care Management; Health Services Administration

Study Officials

• Jason Farley, PhD, MPH, ANP-BC

  The Center for Infectious Disease and Nursing Innovation (CIDNI)

  PRINCIPAL INVESTIGATOR

• Denise Evans, PhD

  University of Witwatersrand, South Africa

  PRINCIPAL INVESTIGATOR

• Norbert Ndjeka, MBChB

  University of Cape Town

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kelly Lowensen, MSN, RN

CONTACT

4104091372; klowens1@jhu.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: We will mask the investigators, statistician and safety review committee to treatment assignment.
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Nurse-led primary care management for patients newly diagnosed with rifampicin-resistant tuberculosis (i.e. intervention) will be compared to physician-led, hospital-based management (i.e. standard of care)

Study Record Dates

• First Submitted: December 20, 2022
• First Posted: January 5, 2023
• Study Start: September 4, 2023
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: October 20, 2025

Record last verified: 2025-10

Locations

ZA (5)