Clinical Research Directory

Phase 2a Multiple Ascending Dose Study in Hospitalized Patients With Pneumonia.

A Phase 2a, randomized, double-blind, placebo-controlled, multiple ascending dose study in patients who are hospitalized with presumed pneumonia requiring supplemental oxygen therapy. The purpose of this study is to examine the safety, tolerability and efficacy of AV-001 Injection administration daily to the earlier of day 28 or EOT (day prior to hospital discharge). A total of 120 eligible patients (20 patients in each of cohort 1, 2 and 3 and 60 patients in cohort 4) will be recruited from up to 25 participating institutions/hospitals. Patients will be randomized in a 1:1 ratio to receive either AV-001 Injection or AV-001 placebo Injection, together with standard of care (SOC).

Post Authorization Efficacy and Safety Study (PAES) to Confirm and Collect More Clinical Data of Buccalin® Tablets In the Prophylaxis of Recurrent Lower Respiratory Tract Infections (RLRTIs).

The goal of this clinical trial is to assess if BUCCALIN® works In the Prophylaxis of Recurrent Lower Respiratory Tract Infections (RLRTIS). It will also evaluate the safety of BUCCALIN®. The primary aim is to reduce the number of infection episodes in the treatment period (12 months) in the BUCCALIN® group versus the Placebo group. Patients diagnosed with RLRTIS will be screened for enrolment. Patients will be requested to provide informed consent before the start of the study related assessments. Eligible patients who meet the study inclusion and exclusion criteria will be randomized with a 1:1 ratio allocation to the 2 treatment groups. Researchers will compare BUCCALIN® (gastro-resistant tablets) to a placebo (gastro-resistant tablets containing only excipients) to treat RLRTIS. Patients who participate in the study will perform several study visits divided as reported below: * Run-in phase (12 months): patients will not receive any treatment. This phase is designed to increase adherence to the study and reduce loss to follow-up in the clinical trial. During this phase, patients should experience ≥ 2 episodes of RTIs to be eligible for the Treatment period. * Treatment period (12 months): patients will receive BUCCALIN® or Placebo treatment for 12 consecutive months (3 days per month, posology as per authorized SmPC). * Follow-up period (12 months): patients will not receive any treatment. This phase is designed to observe how patients respond to treatments.

Prospective Clinical Evaluation of the BioFire Emerging Coronavirus Panel for the Detection of COVID-19 and Other Coronaviruses

The Biomedical Advanced Research and Development Authority (BARDA) has contracted BioFire Defense (BFDf) to develop the BioFire Emerging Coronavirus (ECoV) Panel, a nucleic acid test capable of detecting coronaviruses from nasopharyngeal swab (NPS) in transport medium. This study aims to evaluate the diagnostic accuracy of the assays comprising the BioFire ECoV Panel. It is hypothesized that the BioFire ECoV Panel assays will be highly sensitive and specific for the detection of the coronaviruses included on the panel.

Analysis of Nasopharyngeal Microbiota in Patients With Respiratory Infections

Respiratory tract infections represent the most frequent infectious pathology in community environments and when of bacterial origin, imply a morbid state generally supported by a pathogenic bacterial species predominant on the commensal flora of the airways. Among the most frequent bacterial infections of the upper respiratory tract in pediatric age we find acute bacterial pharyngitis or pharyngotonsillitis caused by Streptococcus pyogenes (β-hemolytic group A), for which antimicrobial therapy is clearly indicated, and which manifests itself with an onset sudden fever. It should also be remembered that some forms of pharyngitis are caused by Chlamydia pneumoniae, Mycoplasma pneumoniae, Bordetella pertussis and Legionella, commonly responsible for lower respiratory tract infections but recently also associated with upper respiratory tract infections. In childhood, a viral or bacterial infection of the upper respiratory tract (in particular pharyngitis, laryngitis) can easily lead to an infection of the lower respiratory tract (pneumonia). In fact, the inflammatory process triggered by a previous infection, generally viral, determines an impairment of mucociliary clearance which facilitates the proliferation not only of pathogenic bacteria but also of the commensal bacterial flora, normally non-pathogenic. An altered local microbial flora can, therefore, contribute to the pathogenesis of new infections or itself be responsible for invasive infections. The microbiota of the upper airways may therefore be a further factor influencing the susceptibility, frequency and severity of acute respiratory diseases. The oropharyngeal microbiota is in fact made up of numerous bacterial species which, by colonizing this anatomical tract, interact with the mucosa of the pharynx and therefore with the immune system, contributing to the homeostasis of the upper respiratory tract and consequently also preserving the integrity of the lower respiratory tract. As observed for other anatomical sites, the composition of the oropharyngeal microbiota is conditioned by external events, among which we find the use of antibiotics or oral disinfectant drugs which can favor the development of pathogenic microorganisms. Characterizing the oropharyngeal microbiota in a state of acute and/or chronic respiratory infection could increase knowledge on the microbiological signature associated with such infections and ineffective antibiotic treatments. Greater knowledge of it, also with future corrective purposes, as has now been demonstrated for other body areas, could be of great help in reducing the risk of acute recurrent disease and/or chronic consequences.

Nationwide Research on the Rewilding of Kindergarten Yards

Biodiversity is essential for nature and human well-being. Land use has reduced biodiversity in cities that is associated with altered commensal microbiota and a rising burden of immunological disorders among urban children. The investigators will estimate how rewilding of kindergarten yards affects commensal microbiome, prevalence of allergies, asthma, atopic dermatitis and infections, cortisol levels, cognitive skills and plasma cytokine levels of children. Our specific aims are: To assess if rewilding diversifies health-associated skin, saliva and gut microbiota and reduces infectious diseases and atopic or allergic symptoms. Assess whether the rewilding has positive effects on cognitive skills. Assess whether the rewilding changes cortisol and plasma cytokine levels. The investigators will recruit altogether 320 (160 per treatment) study subjects aged between 1-5 to questionnaire study (Task 2), from which 120 study subjects will be analyzed more detailed using microbiological and blood samples (Task 1).

Early Diagnosis of Invasive Lung Aspergillosis

The last decade has seen a significant increase in secondary Aspergillus infections, not only due to primary hypersensitivity, and immunodeficiency based on oncological diseases and their therapy, but mainly due to a rise in severe respiratory infections (H1N1, COVID-19, bacterial infections). This is most evident in critically ill patients whose life is threatened by invasive pulmonary aspergillosis (IPA), with over 90 % of cases being caused by Aspergillus fumigatus. In recent decades, various biomarkers with well-known limits of use (Aspergillus DNA, galactomannan, 1,3-ß-D-glucan) have been used for early diagnosis of IPA. However, the clinical need to clearly distinguish the onset of IPA from colonization is much more significant. The current biomarkers only provide "probable IPA" interpretation, and the diagnosis is rarely confirmed. Based on our preliminary studies, the use of new low molecular weight substances (secondary metabolites) combined with acute-phase proteins (pentraxin 3) allows very reliable immediate confirmation of IPA. In tissue samples, bronchoalveolar lavage fluid, endotracheal aspirate, breath condensate, serum, and urine of critically ill patients, the investigators will be able to recognize and confirm IPA in time using highly sensitive mass spectrometry detecting specific microbial siderophores in correlation with a significantly increased concentration of acute-phase host protein (pentraxin 3) within hours of the beginning of the invasion of lung tissue. Through a prospective multicentre study, the investigators will evaluate the benefit of new biomarkers in non-invasive IPA confirmation, improve the IPA diagnostic algorithm and transfer the detection method to MALDI-TOF spectrometers widely used in Clinical laboratories in the Czech Republic. In MALDI-TOF mass spectrometry, the ion source is matrix-assisted laser desorption/ionization (MALDI), and the mass analyser is a time-of-flight (TOF) analyser. The study results will contribute to a high clarity of IPA cases, the accurate introduction of antifungal therapy, and a better prognosis of survival of critically ill patients.