STRATIFIED HOST-DIRECTED THERAPY
FOR DRUG-RESISTANT TUBERCULOSIS
Tuberculosis has historically been the most common infectious cause of death globally, surpassed only recently (and presumably temporarily) by the ongoing Covid-19 pandemic. TB treatment is lengthy and often unsuccessful. Most patients are left with impaired lung function and shortened longevity even if cured. This project evaluates two adjunctive host-directed therapies in patients with rifampin-resistant tuberculosis (RIF-R-TB) in a phase 2 clinical trial. RIF-R-TB patients are at increased risk of death, treatment failure, and impaired post-TB lung function. The trial’s two experimental arms add either CC-11050 (a type 4 phosphodiesterase inhibitor that reduces inflammation by increasing cellular levels of cyclic AMP) or metformin (an AMPK activator used to treat diabetes mellitus that alters cellular metabolism) to standard RIF-R-TB treatment. A control arm receives standard RIF-R-TB treatment alone. The experimental arms are each compared individually to the control arm. The study’s two co-primary endpoints examine lung function (FEV1, in a superiority comparison) and sputum culture conversion (the likelihood of sputum culture conversion expressed as a hazard ratio, in a non-inferiority comparison).
Aurum is an independent non-profit institute dedicated to solving health problems of the poor through research and implementation. It is based in Johannesburg, South Africa. Aurum has overall responsibility for this project.
The Swiss Tropical and Public Health Institute is an international public health institute working in various disciplines with a particular focus on low- and middle-income countries. Swiss TPH will assess the social and economic impact of TB, and will assist in clinical trial monitoriing.
Ludwig Maximilian University of Munich is a German public research university. LMU is responsible for Data Management and Statistics, and will assist in spirometry training.
The Research Center Borstel – Leibniz Lung Center is a German interdisciplinary biomedical research institution located in Borstel. FZB will perform centralized molecular and phenotypic test on MTB isolates and will participate in clinical activities.
The University of Antwerp is a major Belgian university. UA will assist in performing centralized molecular and phenotypic testing of MTB isolates, through its collaboration with Stellenbosch University in South Africa.
The Marius Nasta Institute of Pneumophthisiology (IPMN) is the largest tertiary hospital in Bucharest dedicated to lung pathology in Romania. It will participate in clinical activities in this project.
The Phthisiopneumology Institute (IFP CD) of Chisinau is the main research institution and republican clinical structure in the field of tuberculosis control from Moldova. It will participate in clinical activities in this project.
The Georgia National Center of Tuberculosis and Lung Diseases (NCTLD) was founded in 2001 as a Center of Excellence for specialized TB services in Tiblisi Georgia. It will participate in clinical activities in this project.
The Instituto Nacional de Saúde (INS), Ministry of Health, Mozambique, is a public health research institution, focusing on epidemiological surveys and conduct of clinical trials. It will participate in clinical activities in this project.
The Wits Health Consortium (Pty) Limited (WHC) is wholly-owned by the University of the Witwatersrand. WHC supports operations through which the University - primarily its Faculty of Health Sciences - conducts research, manages donor-funded activities, pursues entrepreneurial innovation in health and supports clinical trials. Its Empilweni TB Hospital will participated in clinical activities in this project.
This project is support by Horizon 2020 grant 847465 for Research and Innovation