Clinical Trials

Two clinical trials are performed within the HDM-FUN project:

Safety and Efficacy of Recombinant Interferon-Gamma 1b (rIFN-Gamma 1b) Given With Standard Therapy in Patients With Candidemia.

The aim of this study is to design and perform a clinical trial with immunotherapy based on knowledge gained over recent years, namely that patients with candidemia might benefit from immunotherapy with recombinant IFNγ (rIFNγ). We have performed clinical pilot studies, which suggest rIFNγ might be beneficial for outcome. This host-directed medicine approach probably is unlikely to fit all patients, and therefore we need to develop strategies that can categorize the patients who will benefit from this type of immunotherapy. Since this is the first clinical study on host-directed immunotherapy in this area, it is yet unknown which biomarkers from WP5, 6 and 7 are optimal to stratify patients for host-directed immunotherapy. Therefore, all patients with candidemia are randomized between adjunctive rIFNγ immunotherapy (100g subcutaneous three times a week for two weeks) or placebo in addition to standard of care antifungal therapy (SOC), for a post-hoc identification of relevant biomarkers affecting clinical outcome. Patients receive antifungal therapy according to ESCMID/EFISG (Europe) or IDSA (US) guidelines. This is a multifaceted trial that is able to compare different host-pathogen factor-based tests that can guide an immunotherapeutic approach in patients with invasive fungal infection with a well-controlled arm.

 

 

A prospective multi-center observational study to assess the incidence of influenza-associated aspergillosis (IAA) in ICU patients and to identify host- and pathogen related risk factors for IAA in EORTC negative ICU patients with severe influenza.

Invasive pulmonary aspergillosis (IPA) is an important life-threatening infection among immunosuppressed hosts. Classic risk factors, as defined by the EORTC in 2008, include stem cell and solid organ transplant patients, prolonged neutropenia and use of corticosteroid or other immunosuppressive therapy. However, IPA has recently been appreciated as an emerging disease in patients without a typical predisposing immunodeficiency, such as critically ill patients admitted to an intensive care unit (ICU). Recently, we identified severe influenza as an independent risk factor for invasive aspergillosis in the ICU. Based on a retrospective observational study in Belgium and the Netherlands (PMID: 30076119), the incidence of IAA in critically ill influenza patients was 32% in EORTC positive versus 14% in EORTC negative patients. In the coming years, one can expect that antifungal prophylaxis to reduce IAA might become standard of care in this high-risk group of EORTC positive patients. In this respect, guidelines on antifungal prophylaxis have already been adapted in the Netherlands. Whether patients in the lower IAA risk group of EORTC negative influenza ICU patients would also substantially benefit from antifungal prophylaxis is not clear. Instead of assessing the benefit of giving blind antifungal prophylaxis in this lower risk group, specific host-related risk factors for IAA should be identified in these patients, ultimately leading to host-directed antifungal prophylaxis.

The aim of this study is to conduct the first prospective, multi-center observational study of IAA in EORTC negative influenza patients, in ICUs of 3 major hospitals in Belgium, 3 in The Netherlands and 6 in France, over 4 influenza seasons. We employ a strict case definition for IAA and clearly define disease characteristics and risk factors, in a manner that was infeasible in earlier, retrospective studies.

Based on the available budget and inclusion capacity of the participating clinical centres, we anticipate to include at least 50 severe influenza patients with IAA and ~300 patients without IAA (see patient recruitment scheme below). Clinical data and samples arecaptured from patients with and without IAA, and used to identify clinical risk factors for IAA as defined in the WPs of HDM-FUN.

Patient recruitment scheme.