Clinical Trials – TB - Current studies

New diagnostic techniques and shorter treatment to address TB in SA

South Africa’s high tuberculosis (TB) burden and the high HIV incidence results in significant morbidity and mortality. The diagnosis of TB in HIV co-infected individuals has been complicated by paucibacillary infection leading to sputum AFB negative TB. 

Diagnosing TB can be challenging in HIV positive individuals as many have paucibacillary pulmonary disease. Development of new diagnostic techniques are important as well as the development of shorter treatment regimens.

A focus of the research activity of CHRU has been to establish alternative diagnostic methods, as well as the initiation of ART in patients presenting tuberculosis (TB).

CHRU also aims to:

  • Impact on the treatment of HIV and TB including M/XDR TB by evaluating novel treatment strategies for HIV and co-morbidities, including new drugs for HIV treatment
  • Improve the diagnosis and treatment of tuberculosis, including those co-infected with HIV
  • Transform tuberculosis therapeutics by optimizing regimens both to prevent and treat.

CHRU’s research activities around TB are integrated with South Africa’s National TB Program (NTP).

The main clinical trials in TB that are currently underway are listed below:

NCT03086486

Protocol number title: A Phase 3 partially-blinded, randomized trial assessing the safety and efficacy of various doses and treatment durations of linezolid plus bedaquiline and pretomanid in participants with pulmonary infection of either extensively drug-resistant tuberculosis (XDRTB), pre-XDR-TB or treatment intolerant or non-responsive multidrug resistant tuberculosis (MDR-TB).

Study name and site PI Interventional / Observational Closed/ Ongoing Start/
end date
Network Funders/ sponsors
NC007 – ZeNIX in Durban Dr Nosipho Ngubane Interventional Enrolling January 2018 TB Alliance TB Alliance
NC007 – ZeNIX in PE Dr Nicola Wattrus Interventional Enrolling October 2018 TB Alliance TB Alliance
NC007 – ZeNIX in Johannesburg (Sizwe Tropical Disease Hospital) Dr Pauline Howell Interventional Enrolling January 2018 TB Alliance TB Alliance

NCT02906007

Protocol number title: A Phase I/II, Open-Label, Single Arm Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Bedaquiline (BDQ) in Combination with Optimized Individualized Multidrug-Resistant Tuberculosis (MDR-TB) Therapy in HIV-Infected and HIV-Uninfected Infants, Children and Adolescents with MDR-TB Disease.

PI Interventional / Observational Closed/ Ongoing Start/
end date
Network Funders/ sponsors
Dr Pauline Howell Interventional Enrolling 2018 IMPAACT (TBTC) National Institution of Health and Research

NCT02410772

Protocol number title: Rifapentine-Containing, Treatment-Shortening Regimens for Pulmonary Tuberculosis: A Randomized, Open-label, Controlled, Phase 3 Clinical Trial.

Currently, treatment for TB takes at least six months and it is not uncommon for patients to stop therapy once they feel better before completing treatment. This increases the risk of relapse and/or development of resistance to TB drugs. By expediting TB treatments, enormous benefits will be reaped by patients and healthcare systems. The best possible outcome would be that the two four-month, short-course regimens prove to be as good, if not better than current standard six-month TB therapy.

PI Interventional / Observational Closed/ Ongoing Start/
end date
Network Funders/ sponsors
Dr Badal-Faesen Interventional Ongoing 2016 – current ACTG Network and the Tuberculosis Trials Consortium (TBTC) National Institution of Health and Research

NCT02409290

Protocol number title: The STREAM Stage 1 multi-drug resistant (MDR) TB randomised clinical trial – The evaluation of a standardised treatment regimen of anti-tuberculosis drugs for patients with MDR-TB

This is the first study to test the efficacy, safety and economic impact of a standardised shorter MDR-TB regimen. It demonstrates the importance of assessing treatment regimens in Phase III clinical trials in order to understand their potential and limitations. Interim results highlight the importance of a patient-centred approach to MDR-TB care, according to WHO recommendations. This includes early diagnosis, use of appropriate regimens, measures to support medication adherence, comprehensive patient support and close treatment monitoring.

Study site PI Interventional / Observational Closed/ Ongoing Start/
end date
Network Funders/ sponsors
Sizwe Tropical Disease Hospital – Johannesburg Dr Conradie Interventional Ongoing 2012- current N/A MRC and World Lung Union and Janssen

NCT

Protocol number title: The evaluation of a standard treatment regimen of anti-tuberculosis drugs for patients with MDR-TB.

The main aim of this study is to assess whether the proportion of patients with a favourable efficacy outcome on the study regimen is not inferior to those on the control regimen (WHO approved MDR-TB). It also aims to compare the proportion of patients who experience grade 3 or greater adverse events, during treatment and follow-up.

Study site PI Interventional / Observational Closed/ Ongoing Start/
end date
Network Funders/ sponsors
Johannesburg – Helen Joseph Dr Rassool Interventional Ongoing 2016 -current MRC and World Lung Union and Janssen MRC and World Lung Union and Janssen
Durban – King Dinizulu Dr Ngubane Interventional Ongoing 2016 -current MRC and World Lung Union and Janssen MRC and World Lung Union and Janssen

NCT03251196

Protocol number title: Pathogenesis and risk factors of long-term sequelae of pulmonary TB defining individual outcomes and public health impact.

The TB Sequel Study is a multi-country, multi-centre observational cohort study, conducted at four sites in four African countries. CHRU is playing a central role in this study. TB is a global health emergency. It is likely that TB patients from resource-constrained settings, who present with more extensive disease, are left with greater lung impairment.

This study aims establish the basis of the long-term clinical consequences of pulmonary TB, with a particular focus on lung injury. The study aims to:

  • Advance the understanding of the clinical, microbiologic, and host immune factors affecting or predicting the long-term sequelae and socio-economic impact of pulmonary tuberculosis and treatment outcome
  • Identify the most important factors that contribute to lung impairment, including the immunological response and genetic predisposition of the host and differences in the biology of the pathogen, and
  • Facilitate novel interventions to restore and preserve overall health and wellbeing in patients with TB.
PI Interventional / Observational Closed/ Ongoing Start/
end date
Network Funders/ sponsors
Dr Rassool Interventional Ongoing 2017-current TB Sequel German Federal Ministry of Education and Research administered by the BMBF German Centre for Infection Research and the AURUM Institute

NCT02333799

Protocol number title: A Phase 3 randomized, open-label trial assessing the safety and efficacy of bedaquiline plus PA-824 plus linezolid in subjects with pulmonary infection of either extensively drug-resistant tuberculosis (XDR-TB), or treatment intolerant / non-responsive multi-drug resistant tuberculosis (MDR-TB).

There is currently no cure for XDR-TB and is emerging as a deadly and costly global health threat. Treatment of XDR-TB lasts two years or longer and consists of thousands of pills plus injections with horrible side effects. This is the world’s first clinical trial to study an XDR-TB drug regimen with minimal pre-existing resistance. This study focuses on testing a new potential treatment for extensively drug-resistant XDR-TB, a strain of tuberculosis that is airborne, infectious and resistant to four commonly used anti-TB drugs. If successful, the injection-free regimen being tested could transform XDR-TB treatment. Patients may be cured by taking a relatively short, simple and effective regimen. The regimen being tested could reduce the complexity and cost of the treatment, facilitating the global implementation of XDRTB treatment in resource-poor nations.  Both the Sizwe Tropical Disease Hospital and King DinuZulu Hospital sites have been involved in the NIX trial, which used three novel agents for the treatment of XDR TB and represented a major breakthrough.

Study site PI Interventional / Observational Closed/ Ongoing Start/
end date
Network Funders/ sponsors
Nix-TB (Johannesburg) Dr Howell Interventional Ongoing 2015 – current TB Alliance TB Alliance
Nix-TB (Durban) Dr Ngubane Interventional Ongoing 2017 – current TB Alliance TB Alliance

NCT03338621

Protocol number title: An Open-Label, Partially Randomized Trial to Evaluate the efficacy, safety and tolerability of a 4-month treatment of Bedaquiline plus Pretomanid plus Moxifloxacin plus Pyrazinamide (BPaMZ) Compared to a 6-month treatment of HRZEIHR (Control) in Adult Participants with Drug-Sensitive Smear-Positive Pulmonary Tuberculosis (OS-TB) and a 6-month treatment of BPaMZ in Adult Participants with Drug Resistant, Smear-Positive Pulmonary Tuberculosis (DR-TB).

Study site PI Interventional / Observational Closed/ Ongoing Start/
end date
Network Funders/ sponsors
Durban – King Dinizulu Hospital Dr Nosipho Ngubane Interventional Ongoing Started July 2018 TB Alliance TB Alliance
Johannesburg – Helen Joseph Hospital Dr Mohammed Rassool Interventional Started Dec 2018 TB Alliance TB Alliance
Port Elizabeth site Dr Nicola Wattrus Interventional Started Oct 2018 TB Alliance TB Alliance

NCT02968927

Protocol number title: Host-directed therapies for tuberculosis.

This study examines if adding host-directed therapy to standard antimicrobial treatment could result in a shorter and improved treatment of TB.It also aims to examine the safety and preliminary efficacy of multiple adjunctive host directed TB therapies (TB HDT), and to assess their potential to shorten TB treatment and/or prevent permanent lung damage.

PI Interventional / Observational Closed/ Ongoing Start/
end date
Network Funders/ sponsors
Dr Rassool Interventional Ongoing 2016 N/A The Aurum Institute and the Gates Foundation

NCT03086486

Protocol number/ title: A Phase 3 trial partially-blinded, randomized trial assessing the safety and efficacy of various doses and treatment durations of linezolid plus bedaquiline and pretomanid in participants with pulmonary infection of either extensively drug-resistant tuberculosis (XDRTB), pre-XDR-TB or treatment intolerant or non-responsive multidrug resistant tuberculosis (MDR-TB).

Study site PI Interventional / Observational Closed/ Ongoing Start/
end date
Network Funders/ sponsors
NC007 – ZeNIX (Sizwe) Dr Pauline Howell Intervention Enrolling Jan-18 TB Alliance TB Alliance
NC007 – ZeNIX (Durban) Dr Nosipho Ngubane Intervention Enrolling Jan-18 TB Alliance TB Alliance
NC007 – ZeNIX (Empilweni – PE) Dr Nicola Wattrus Intervention Enrolling Oct-18 TB Alliance TB Alliance

NCT03568383

Protocol number/ title: Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients (PHOENIx MDR-TB)

Principal Investigator (PI) Interventional / Observational Closed/ Ongoing Start/
end date
Network Funders/ sponsors
Dr Badal-Faesen Interventional PENDING 2019 AIDS Clinical Trials Group (ACTG) National Institutes of Health (NIH)

NCT02906007

Protocol number/ title: A Phase I/II, open-label, single arm study to evaluate the pharmacokinetics, safety and tolerability of Bedaquiline (BDQ) in combination with optimized individualized multidrug-resistant tuberculosis (MDR-TB) therapy in HIV-infected and HIV-uninfected infants, children and adolescents with MDR-TB Disease.

Principal Investigator (PI) Interventional / Observational Closed/ Ongoing Start/
end date
Network Funders/ sponsors
Dr Pauline Howell Interventional Enrolling 2018 IMPAACT National Institute of Allergy and Infectious Diseases (NIAID)

NCT to be confirmed

Protocol number/ title: An open label, randomized controlled trial to establish the efficacy and safety of a Study Strategy consisting of 6 months of bedaquiline (BDQ), delamanid (DLM), and linezolid (LNZ), with levofloxacin (LVX) and clofazimine (CFZ) compared to the current South African Standard of Care (Control Strategy) for 9 months for the treatment of rifampicin resistant tuberculosis (RR-TB)

Principal Investigator (PI) Interventional / Observational Closed/ Ongoing Start/
end date
Network Funders/ sponsors
Dr Francesca Conradie Interventional Closed/ Ongoing July 2018 USAID USAID

NCT02589782

Protocol number/ title: Pragmatic Clinical Trial for a more Effective Concise and Less toxic MDR-TB treatment regimen(s) (TB-PRACTECAL)

Study site PI Interventional / Observational Closed/ Ongoing Start/
end date
Network Funders/ sponsors
TB-PRACTECAL (Durban) Dr Nosipho Ngubane Interventional Current 2019 – Q2 Médecins Sans Frontières Médecins Sans Frontières
TB-PRACTECAL (HJH) Dr Mohammed Rassool Interventional Current 2019 – Q2 Médecins Sans Frontières Médecins Sans Frontières

Protocol number/ title: Rifapentine-Containing, Treatment-Shortening Regimens for Pulmonary Tuberculosis: A Randomized, Open-label, Controlled, Phase 3 Clinical Trial

Principal Investigator (PI) Interventional / Observational Closed/ Ongoing Start/
end date
Network Funders/ sponsors
Dr Badal-Faesen Interventional Follow-up 2016 AIDS Clinical Trials Group (ACTG) National Institutes of Health (NIH)