MDR-TBNCT02129244
A Nurse Case Management Intervention to Improve MDR-TB/HIV Co-Infection Outcomes
A study testing NCM-Plus in people with MDR-TB and HIV, run by Johns Hopkins University at 15 sites in South Africa.
Trial summary
The researchers of this study are observing the treatment of multi-drug resistant Mycobacterium tuberculosis (MDR-TB) in South Africa. MDR-TB can not be treated with the usual TB drugs and needs to be treated with special drugs. The patients need to take these drugs for up to two years. Read more about this study
- Who is it for?
- Ages 13 years and older
- What is being tested?
- NCM-Plus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,844 participants
- Where
- 15 sitesSouth Africa
- Study dates
- Oct 2014to Dec 2025
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Center (Cluster Level)
- MDR-TB Centers in KwaZulu-Natal (KZN) or Eastern Cape (EC), South Africa providing standardized
- MDR-TB regimen according to National Department of Health guidelines
- Facility has provided MDR-TB care for a minimum of 6 months at study initiation
- MDR-TB Centers with facility-based access to anti-retroviral therapy
- Facility willingness to participate in the study
Show all 9Show fewer
- Individual (Patient Level)
- Patients 18 years of age and older, with microbiologically confirmed MDR- TB, admitted to receive inpatient care at a participating hospital who signs informed consent within 7 days of admission.
- Patients 13 - 17 years of age, with microbiologically confirmed MDR- TB, who provide consent for study team to contact parent or legal guardian and when patient is willing and parent or legal guardian provides approval for study participation within 7 days of admission.
Who cannot join
- Persons who present to the MDR-TB ward who have started MDR-TB treatment prior to admission.
- Children, less than 13 years of age; only one participating center has an MDR-TB wards for children under 13.
- Persons who are unable or unwilling to provide informed consent for participation
- Any patient enrolled in another clinical trial that changes standard MDR- TB or HIV care.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
South Africa15 sites
Catherine Booth Hospital
aMatikulu, KwaZulu-Natal
Don McKenzie
Durban
King George V Hospital
Durban
Fort Gray Hospital
East London
Dunstan Farrell Hospital
Hibberdene
Hlabisa Hospital
Hlabisa
Manguzi
Manguzi
Nkqubela
Mdantsane
Fosa Hospital
Newlands West
Doris Goodwin Hospital
Pietermaritzburg
Marjorie Parrish Hospital
Port Alfred
Jose Pearson Hospital
Port Elizabeth
Murchison Hospital
Port Shepstone
St Margaret's MDR-TB Hopsital
Umzimkulu
Regus Primary Office
Westville, Durban, 3629
About this study
The researchers of this study are observing the treatment of multi-drug resistant Mycobacterium tuberculosis (MDR-TB) in South Africa. MDR-TB can not be treated with the usual TB drugs and needs to be treated with special drugs. The patients need to take these drugs for up to two years. Certain hospitals have already agreed to participate in this research project, half of the hospitals will be assigned a nurse case manager and the other half will not. The researchers are studying the benefits of having a nurse case manager to improve treatment response for patients with drug resistant TB. The researchers believe that nurse case management (NCM) in the intervention sites will increase MDR-TB cure and completion rates (i.e. treatment success) in comparison to usual care (UC), i.e. standardized programmatic management alone, in patients with and without HIV co-infection. To do this, the researchers will review the medical information collected at the hospital as part of the patient's treatment after obtaining the patient's permission.
Read the detailed description
Mycobacterium tuberculosis (TB) remains the leading cause of death among persons living with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) in southern Africa. This syndemic places an overwhelming burden on healthcare workers and the health system. Drug-resistant TB remains a growing threat to public health despite advances in treatment and diagnosis over the past decade. South Africa has the world's highest rate of TB/HIV co-infection and ranks fourth worldwide for both multi-drug resistant (MDR) TB incidence and HIV prevalence. Treatment of MDR-TB, defined as resistance to isoniazid and rifampin, remains challenging and its treatment course complex. Success of second line treatment regimens is considerably less likely than first line treatment with significantly more adverse drug reactions (ADRs). Prospective cohort studies from South Africa report less than 50% treatment success (i.e. cure or completion) and significant differences in patients with and without HIV are noted. Differences in sex and gender as well as age are rarely evaluated. In addition to the management complexity and length of treatment, systems level factors such as access to care and healthcare capacity contribute to poorer treatment outcomes. Insufficient numbers of trained physicians capable and clinically competent to manage the challenges of integrated MDR-TB/HIV care are commonplace. These circumstances place a heavy burden on the most abundant healthcare resource in South Africa, the nurse. Nurses with proficiency in care models for both diseases are essential to improve treatment outcomes. The investigators experience dictates, however, that patients endure lengthy treatment with little assessment, support or guidance from nursing professionals due to a lack of training as well as lack of evidence-based interventions and delineated models of care for MDR-TB patients.
Nurse case management (NCM) models in which a registered nurse facilitates and coordinates treatment plans to ensure that timely, evidence-based care is given improves treatment outcomes. Presently, there is little evidence to describe such models in TB/HIV co-infected patients globally, and specifically less evidence for MDR-TB/HIV in sub-Saharan Africa. Many studies, however, have demonstrated substantial improvements in disease outcomes utilizing nurse case managers. Complex diseases such as heart failure, diabetes, HIV and drug susceptible TB are among these. Substantial gaps remain, however, in the investigators understanding of the impact of such interventions among co-infected patients, the influence of such models among different age groups or the cost-benefit in under resourced settings. Prior studies provide strong evidence that interventions must be multi-faceted and foster system level approaches to improve treatment outcomes (i.e. NCM patient-centered care services coupled with systems level approaches to care coordination). The Chronic Care Model identifies essential elements of a health care system that encourage high-quality chronic disease care in such a systems approach. These elements provide the conceptual model and implementation structure for the proposed NCM plus health systems strengthening (i.e. NCM-plus) intervention, a multi-faceted health systems and patient-centered intervention to improve MDR-TB/HIV treatment outcomes. The proposed 5-year cluster randomized trial, will evaluate the NCM-plus intervention on MDR-TB treatment outcomes in South Africa, the epicenter of the MDR-TB/HIV epidemic.
Primary Aim:
To determine the impact of a NCM model (i.e. NCM-Plus) on MDR-TB outcomes in patients with and without HIV co-infection in South Africa through a cluster randomized trial.
Hypothesis:
Nurse case management (NCM) in intervention sites will increase MDR-TB cure and completion rates (i.e. treatment success) in comparison to usual care (UC), i.e. standardized programmatic management alone, in patients with and without HIV co-infection.
Secondary Aims:
- To conduct sub-group analysis by a) HIV co-infection; b) sex and gender; and c) age
- To compare the frequency and time to identification of adverse drug events between intervention and control sites.
- To conduct a costing analysis and a cost-effectiveness evaluation of the intervention.
- Being tested
- NCM-Plus
- Keywords
- MDR-TB, HIV, Nurse Case Management (NCM)
- Medical subject headings
- Tuberculosis, Multidrug-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NCM-PlusOther
The NCM will follow the domains of the chronic care model by:
- Assuring effective, efficient clinical care and self-management support
- Promoting clinical care consistent with scientific evidence and patient preferences
- Organizing data to facilitate efficient, effective care
- Empowering and preparing patients to manage their health and health-care needs
- Mobilizing community resources to meet the needs of patients
| Study group | Role | What they receive |
|---|---|---|
| NCM Plus Intervention | Active comparator | The researchers designed the NCM-Plus intervention by integrating the domains of the Chronic Care Model with added attention to linkage to care, building on evidence-based guidelines and the team's pilot findings. In the NCM bundle, the researchers provide extensive details on both proximal and distal outcome variables. Nurse case managers will be hired and trained to improve disease management for patients with MDR-TB and HIV. Specific measurable responsibilities will be implemented by each NCM at sites randomized to receive the intervention. The NCM-patient interaction will occur at the MDR-TB treatment inpatient or outpatient facility. Receives: Other: NCM-Plus |
| Standard/Usual Care | No intervention | Usual care is defined as standardized programmatic management of MDR-TB/HIV without care coordination. Nurses are present as part of the team, but with no special coordination role, leaving the MDR-TB physician solely responsible for treatment outcomes with little support. Physicians see patients weekly during the intensive phase and the patient receives basic daily nursing care without coordination of care, active monitoring of Adverse Drug Reactions (ADR)s or HIV care integration. This care transitions to monthly visits with the physician in the continuation phase, again with very little nursing involvement in care coordination. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patients Who Experience Successful Treatment Outcomes
Patients who experience successful treatment outcomes
Measured: 36 months
Secondary outcomes (3)
Patients Who Experience Successful Treatment Outcomes Based on HIV Co-infection
Multivariate Analysis using binomial or Poisson-based GEE models
Measured: 36 months
Patients Who Experience Successful Treatment Outcomes Based on Sex and Gender
Multivariate Analysis using binomial or Poisson-based GEE models
Measured: 36 months
Patients Who Experience Successful Treatment Outcomes Based on Age
Multivariate Analysis using binomial or Poisson-based GEE models
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2014 (estimated)
- Study startOct 2014
- Primary completionMar 2021
- Study completionDec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (61)Papers the sponsor has linked to this study.
- Other trials for MDR-TBStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,844 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID), Medical Research Council, South Africa
- Responsible party
- Sponsor
- Investigators
- Jason E Farley, PhD, MPH, NP, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02129244
- Sponsor's protocol ID
- NA_00078899
- Other IDs
- RO1 104488-01A1
- Status last verified
- Sep 2026
- First submitted
- 29 Apr 2014
- Last updated
- 6 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
World Health Organization. Global Tuberculosis Control. WHO/HTM/TB/2010.7. 2010. Geneva, Switzerland.
World Health Organization. Multidrug and extensively drug-resistant TB (M/XDR-TB): 2010 global report on surveillance and response. [WHO/HTM/TB/2010.3]. 2010. World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland, WHO Press.
Orenstein EW, Basu S, Shah NS, Andrews JR, Friedland GH, Moll AP, Gandhi NR, Galvani AP. Treatment outcomes among patients with multidrug-resistant tuberculosis: systematic review and meta-analysis. Lancet Infect Dis. 2009 Mar;9(3):153-61. doi: 10.1016/S1473-3099(09)70041-6.
PubMed 19246019Johnston JC, Shahidi NC, Sadatsafavi M, Fitzgerald JM. Treatment outcomes of multidrug-resistant tuberculosis: a systematic review and meta-analysis. PLoS One. 2009 Sep 9;4(9):e6914. doi: 10.1371/journal.pone.0006914.
PubMed 19742330Farley JE, Ram M, Pan W, Waldman S, Cassell GH, Chaisson RE, Weyer K, Lancaster J, Van der Walt M. Outcomes of multi-drug resistant tuberculosis (MDR-TB) among a cohort of South African patients with high HIV prevalence. PLoS One. 2011;6(7):e20436. doi: 10.1371/journal.pone.0020436. Epub 2011 Jul 22.
PubMed 21799728Shean KP, Willcox PA, Siwendu SN, Laserson KF, Gross L, Kammerer S, Wells CD, Holtz TH. Treatment outcome and follow-up of multidrug-resistant tuberculosis patients, West Coast/Winelands, South Africa, 1992-2002. Int J Tuberc Lung Dis. 2008 Oct;12(10):1182-9.
PubMed 18812049Gandhi NR, Shah NS, Andrews JR, Vella V, Moll AP, Scott M, Weissman D, Marra C, Lalloo UG, Friedland GH; Tugela Ferry Care and Research (TF CARES) Collaboration. HIV coinfection in multidrug- and extensively drug-resistant tuberculosis results in high early mortality. Am J Respir Crit Care Med. 2010 Jan 1;181(1):80-6. doi: 10.1164/rccm.200907-0989OC. Epub 2009 Oct 15.
PubMed 19833824Somma D, Thomas BE, Karim F, Kemp J, Arias N, Auer C, Gosoniu GD, Abouihia A, Weiss MG. Gender and socio-cultural determinants of TB-related stigma in Bangladesh, India, Malawi and Colombia. Int J Tuberc Lung Dis. 2008 Jul;12(7):856-66.
PubMed 18544216O'Donnell MR, Zelnick J, Werner L, Master I, Loveday M, Horsburgh CR, Padayatchi N. Extensively drug-resistant tuberculosis in women, KwaZulu-Natal, South Africa. Emerg Infect Dis. 2011 Oct;17(10):1942-5. doi: 10.3201/eid1710.110105.
PubMed 22000378Vella V, Racalbuto V, Guerra R, Marra C, Moll A, Mhlanga Z, Maluleke M, Mhlope H, Margot B, Friedland G, Shah NS, Gandhi NR. Household contact investigation of multidrug-resistant and extensively drug-resistant tuberculosis in a high HIV prevalence setting. Int J Tuberc Lung Dis. 2011 Sep;15(9):1170-5, i. doi: 10.5588/ijtld.10.0781.
PubMed 21943840National Department of Health, South Africa. Decentralized Management of Multi-Drug Resistant Tuberculosis: A Policy Framework for South Africa. 2011.
Welch G, Garb J, Zagarins S, Lendel I, Gabbay RA. Nurse diabetes case management interventions and blood glucose control: results of a meta-analysis. Diabetes Res Clin Pract. 2010 Apr;88(1):1-6. doi: 10.1016/j.diabres.2009.12.026. Epub 2010 Feb 8.
PubMed 20116879Nyamathi A, Nahid P, Berg J, Burrage J, Christiani A, Aqtash S, Morisky D, Leake B. Efficacy of nurse case-managed intervention for latent tuberculosis among homeless subsamples. Nurs Res. 2008 Jan-Feb;57(1):33-9. doi: 10.1097/01.NNR.0000280660.26879.38.
PubMed 18091290Del Sindaco D, Pulignano G, Minardi G, Apostoli A, Guerrieri L, Rotoloni M, Petri G, Fabrizi L, Caroselli A, Venusti R, Chiantera A, Giulivi A, Giovannini E, Leggio F. Two-year outcome of a prospective, controlled study of a disease management programme for elderly patients with heart failure. J Cardiovasc Med (Hagerstown). 2007 May;8(5):324-9. doi: 10.2459/JCM.0b013e32801164cb.
PubMed 17443097Anaya HD, Hoang T, Golden JF, Goetz MB, Gifford A, Bowman C, Osborn T, Owens DK, Sanders GD, Asch SM. Improving HIV screening and receipt of results by nurse-initiated streamlined counseling and rapid testing. J Gen Intern Med. 2008 Jun;23(6):800-7. doi: 10.1007/s11606-008-0617-x. Epub 2008 Apr 18.
PubMed 18421508