Research projects

The FLIRT Trial: A phase III, international, multi-centre, double-blind randomised controlled trial to evaluate the effectiveness of fluoroquinolone-based therapy versus placebo for isoniazid-resistant tuberculosis.

Australian principal investigator: Professor Greg Fox, the University of Sydney

Key stakeholders: National Lung Hospital

Study sites: Hanoi, Ho Chi Minh City, Can Tho

Details: FLIRT Trial is a randomised (1:1), placebo-controlled double-blind multi-centre superiority trial, to compare the proportion of sustained treatment success with the intervention (fluoroquinolone-containing) regimen to that with the comparator regimen, in the modified intention to treat (mITT) population. A total of 920 participants aged ≥ 10 years old, with isoniazid-resistant (INH-R), rifampicin-susceptible (RIF-S) and fluoroquinolone-susceptible pulmonary TB will be recruited at TB clinics in Australia (Sydney), Vietnam and Canada (Montreal and Vancouver) within 24-30 months and followed up in 18 months. This trial is funded by a Clinical Trials and Cohort Studies’ grant from the National Health and Medical Research Council, Australia. The University of Sydney is the international study sponsor.

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

Australian principal investigator: Professor Greg Fox, the University of Sydney

Key stakeholders: National Lung Hospital

Study sites: District 6 Health Care Center, Ho Chi Minh City

Details: PHOENIx MDR-TB is a Phase III, open-label, multicenter trial with a cluster-randomized superiority design (eligible contacts in the same household [HH] are a cluster), to compare the efficacy and safety of 26 weeks of delamanid (DLM) versus 26 weeks of isoniazid (INH) for preventing confirmed or probable active TB during 96 weeks of follow-up among high-risk household contacts (HHCs) of adults with multidrug-resistant tuberculosis (MDR-TB).

There will be approximately 5736 participants enrolled (approximately 1902 index cases and 3834 HHCs) at 13 countries around the world including Vietnam. The trial is funded by National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, supported by Otsuka Pharmaceutical Company, and run by A Multicenter Trial of the AIDS Clinical Trials Group (ACTG) and the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT). 

CRUSH-TB: Phase 2C Clinical Trial of Novel, Short-course Regimens for the Treatment of Pulmonary Tuberculosis

Australian principal investigator: Professor Greg Fox, the University of Sydney

Key stakeholders: National Lung Hospital

Study sites: Can Tho Tuberculosis and Lung Disease Hospital

Details: The purpose of this study is to determine whether one or two 17-week regimens of tuberculosis treatment bedaquiline (B or BDQ), moxifloxacin (M), pyrazinamide (Z)-- (BMZ) plus either Rifabutin (Rb) or Delamanid (D or DLM) are as effective as a standard six-month regimen for treatment of pulmonary tuberculosis (TB). All three regimens are administered daily, seven days each week.

The first 17-week regimen is 2 months of bedaquiline (B or BDQ), moxifloxacin (M), pyrazinamide (Z), (BMZ) plus rifabutin (Rb) (BMZRB) followed by 2 months of bedaquiline (B or BDQ), moxifloxacin (M) and Rifabutin (Rb) (2 BMZRb/2 BMRb, Arm 1)

The Second 17-week regimen is 2 months of bedaquiline (B or BDQ), moxifloxacin (M), pyrazinamide (Z), (BMZ) plus delamanid (D or DLM); (BMZD) followed by 2 months of bedaquiline (B or BDQ), moxifloxacin (M) and delamanid (D or DLM) (2 BMZD/2 BMD, Arm 2)

The standard 26-week treatment control regimen which is two months of isoniazid, rifampin, ethambutol, and pyrazinamide (2HRZE) followed by four months of isoniazid and rifampin (4HR); (2HRZE/4HR, Arm 3)

Target enrollment is 288 male and female participants (96/arm). participants. Participants will be followed until 78 weeks post-randomization, or until the last enrolled participant completes 52 weeks post-randomization, whichever comes first.

This study is funded by Centers for Disease Control and Prevention.

ASTERoiD: Six weeks of daily rifapentine vs. a comparator arm of 12-16 week rifamycin-based treatment of latent M. tuberculosis infection: assessment of safety, tolerability and effectiveness

Australian principal investigator: Professor Greg Fox, the University of Sydney

Key stakeholder: National Lung Hospital

Study sites: Phoi Viet Clinic, Can Tho Tuberculosis and Lung Disease Hospital, District 6 Health Center

Details: This study is conducted to compare the safety and effectiveness of a novel short 6-week regimen of daily rifapentine (6wP, experimental arm) with a comparator arm of 12-16 weeks of rifamycin-based treatment (standard of care, control arm) of latent M. tuberculosis infection (LTBI).

This trial is conducted among persons who are at increased risk of progression to tuberculosis (TB) and require treatment of LTBI. The study will be conducted in low, medium and high TB incidence settings that have treatment of LTBI as their standard of care and offer 12-16 week rifamycin-based therapy as standard of care.

The hypothesis of this study is that the safety and effectiveness of the experimental treatment (6wP arm) is non-inferior to a comparator arm of 12-16 weeks of rifamycin-based treatment of LTBI (control arm).

Participants are enrolled and randomly assigned to one of the two study arms: experimental 6wP or control. The comparator (control) arm's treatment regimens include 12 weeks of once-weekly isoniazid (INH) and rifapentine (3HP), 12 weeks of daily INH and rifampin (3HR), and 16 weeks of daily rifampin (4R). A total of 560 participants per arm (1,120 total) for the evaluation of safety and 1,700 participants per arm (3,400 total) for the evaluation of effectiveness will be enrolled, given treatment as per randomization assignment, and followed for 24 months from the date of enrollment.

After completion of data collection, statistical analyses will be conducted to compare proportions of drug discontinuation due to adverse drug reaction (ADR) and proportions of newly diagnosed tuberculosis between 6wP and control arm.

This study is funded by Centers for Disease Control and Prevention.

SAPPHIRE: SAPPHIRE will (i) scale up the interventions program on TB in Vietnam, focusing on wide community screening, (ii) scale up AMS interventions in agriculture and health sectors, (iii) strengthening chronic diseases  management system.

Australian principal investigator: Professor Greg Fox, the University of Sydney

Key stakeholders: Ministry of Health, Bach Mai Hospital, National Institute of Hygiene and Epidemiology, University of Medicine & Pharmacy HCMC, Can Tho University of Medicine & Pharmacy , Hue University

Study sites: TBC

Details: The consortium submitted to DFAT comprises 2 regional hubs (1) Vietnam-Cambodia and (2)Fiji-Solomons-PNG, providing strategic benefits through connections within and between hubs. 

In the Vietnam-Cambodia hub which will run through SVI, we will (i) scale up the interventions program on TB in Vietnam, focusing on wide community screening, (ii) scale up AMS interventions in agriculture and health sectors, (iii) strengthening chronic diseases  management system. In those 3 areas, cross cutting themes will be applied include capacity building, advocacy, gender inclusion. Lessons learnt will be applied to Cambodia's interventions planning and implementation.

The University of Sydney Vietnam Institute will collaborate with many Vietnamese stakeholders to run this program, which has received funding from the Australian Government Department of Foreign Affairs and Trade.

AETAP-PPI Project: The University of Sydney Vietnam Insistute and partners assist the Ministry of Health and its designated agencies in strengthening its immunisation efforts. 

Australian principal investigator: Professor Greg Fox, the University of Sydney

Key stakeholders: Ministry of Health, National Institute of Hygiene and Epidemiology

Details: The main objectives of this project are to increase COVID-19 vaccine uptake and communication, develop effective vaccine communication strategies, materials and training plans, provide trainers and materials for MOH and UNICEFs training, and provide technical advice to Vietnam's National Technical Advisory Group (NITAG). The project has received funding from received funding from the Australian Government Department of Foreign Affairs and Trade through the National Centre for Immunisation Research Surveillance.

GAVI: This project seeks to provide technical advice to Vietnam National Immunization Technical Advisory Group.

Principal investigator: Professor Thu-Anh Nguyen, the University of Sydney Vietnam Institute

Key stakeholders: Ministry of Health, National Institute of Hygiene and Epidemiology

Details: Key activities of this project are:

1. Providing technical advice to Vietnam National Immunisation Technical Advisory Group, including coaching and advocating for rolling out four new vaccines for adults.

2. Developing context-specific, adaptable, and high-quality training materials for new vaccines.

PREMISE: PREMISE is a digital technology evaluation and assessment study building on data collected prospectively in the V-SMART trial.

Principal investigator: Anh Tran, the University of Sydney

Key stakeholders: National Lung Hospital

Details: PREMISE will examine the preferences and willingness-to-pay for tuberculosis (TB) treatment of patients and clinicians using smartphone-based mobile health (mHealth). 

Results will be used to estimate the lifetime cost-effectiveness of mHealth in augmenting traditional tuberculosis-resistant management in Vietnam. 

PREMISE is funded by a 2023 Sydney South East Asia Centre Collaborative Research Grant.

Investing the Impact of Chronic Pulmonary Aspergillosis in Tuberculosis Survivors: Chronic Pulmonart Aspergillus as a sequel to pulmonary tuberculosis in Vietnam

Principal investigator: Associate Professor Justin Beardsley, the University of Sydney

Key stakeholders: National Lung Hospital

Study sites: National Lung Hospital, Hanoi Lung Hospital, Hospital 74

Details: A prospective observational cohort study of TB survivors in Vietnam to assess incidence of CPA and related health burden. Also observes microbiological features. This study is funded by the National Health and Medical Research Council.