Candi-NET: Integrating Candidaemia trial samples, Data and Infrastructure to define Novel clinical trial Endpoints and Treatment strategies
( Candi-NET )

Interventions

Therapeutics

Research Project: 2025-04-01 - 2028-03-31
Total sum awarded: €1 096 242

The fungal gut commensal Candida is the most common cause of fungal sepsis worldwide, with persistently high (?50%) mortality, contributed to by emerging resistance to first-line antifungal drugs, echinocandins and azoles. Candidaemia clinical trial design is hampered by reliance on binary clinical and mycological endpoints, in which resistance does not feature. We have assembled a unique consortium of 3 European (UK, France, Netherlands) and 1 South African investigator-led, candidaemia clinical cohorts, with Candida clearance and resistance emergence as a cross-cutting theme. By harmonising trial sampling and integrating clinical metadata with diverse -omics datasets from a combined cohort of 600-700 patients, including proteomics, genomics, metabolomics and mycobiome, our methodology will furnish novel, translational insights that will set the CANDI-NET project apart. Our findings will enable patient stratification in clinical trials in candidaemia, as well as validation of biomarkers of pathogen and host treatment response and pathogen resistance emergence as novel clinical trial endpoints. We will establish a network for phase II/III investigator-led trials in Mycology in low (Europe) and high (Southern Africa) Candida resistance burden settings. Our project will thus deliver the infrastructure and tools required to design an adaptive platform trial to test novel interventions to reduce persistently high Candidaemia mortality and mitigate increasing Candida resistance.

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  • Bicanic Tihana, St George's University of London, United Kingdom (Coordinator)
  • Blandine Denis, Assistance Publique Hôpitaux de Paris, France (Partner)
  • Alexandre Alanio, Institut Pasteur, France (Partner)
  • Frank Van de Veerdonk, Radboud University Medical Centre, Netherlands (Partner)
  • Nelesh Govender, University of the Witwatersrand, South Africa (Observer)

Candida is a fungus that usually lives harmlessly in the human gut but can cause severe bloodstream infection (candidaemia) in patients in hospital, resulting in death in ?50% of cases. Increasing resistance to first-line antifungals contributes to this, and new drugs are needed. Current clinical trials to test these agents require hundreds of patients per arm to confidently demonstrate that one drug is better than another in reducing death or clearing infection in candidaemia- and no account is taken of how liable that drug is to development of resistance. To make the process more efficient (quicker at weeding out poor performing drugs at an earlier stage), we need more accurate predictors of which patients will respond to treatment, and measures of that response, so called biomarkers. These could relate to how quickly the Candida fungus is cleared from the body, its propensity to persist and develop resistance, and/or the human immune response against Candida. In this project, led by experienced fungal clinicians and laboratory researchers, we will create an international network to share knowledge and standardise collection of samples, pool and integrate data from 4 European and South African clinical trials in candidaemia (total ?700 patients). We will use novel, cutting-edge laboratory (including genomics and gut fungal microbiome studies) and statistical methods (including machine learning) to analyse our collective samples in order to establish the most accurate biomarkers for use in future trials to determine the best treatment for (antifungal-resistant) Candida.

Call

2024 - Interventions moving forward to promote action to counteract the emergence and spread of bacterial and fungal resistance and to improve treatments