Active clinical trials for "Invasive Pulmonary Aspergillosis"

This study assesses the pharmacokinetics and safety of the new antifungal F901318 in AML patients.

voriconazole is recommended as first-line therapy for invasive pulmonary aspergillosis, however the efficacy and safety of voriconazole for treating invasive pulmonary aspergillosis secondary to COPD is not clear. This study aims to investigate the effectiveness and tolerability of intravenous voriconazole for treatment of invasive pulmonary aspergillosis in Chinese patients with COPD, by monitoring changes in clinical symptoms, eradication of aspergillus, improvement of chest imaging as well as record of possible adverse reactions following 2-week intravenous instillation of voriconazole.

Multiple factors are associated with a large variability in voriconazole exposure following standard dose administration, such as non-linear saturable pharmacokinetics, drug-drug interactions, liver disease, patient age, and genetic polymorphism of the metabolic enzymes. Voriconazole is extensively metabolized by the human hepatic enzymes, primarily mediated by CYP2C19. The polymorphisms account for a relatively large portion of inter-individual variance observed in voriconazole plasma concentrations. However, there are limited data on the relationships between voriconazole blood levels and clinical outcomes or safety in Asian populations. The purpose of this study is to investigate the relationships of voriconazole blood levels with genetic polymorphism, safety, and clinical outcomes in immunocompromised patients with invasive pulmonary aspergillosis.

Study the incidence and outcome of invasive pulmonary aspergillosis (IPA) in ICU patients with severe influenza and in influenza-negative control patients with severe community-acquired pneumonia

Background Invasive pulmonary aspergillosis (IPA) remains an important cause of morbidity and mortality among patients with hemato-oncological malignancies. Due to the crude mortality of >90% in absence of adequate treatment, timely diagnosis and early start of antifungal therapy are key factors in the successful treatment of IPA. Various studies have shown that early initiation of antifungal therapy may improve IPA survival to above 70%. Diagnosis of IPA, however, remains difficult as clinical signs and symptoms as well as radiological findings are often unspecific and conventional culture methods lack sensitivity. In recent years antigen testing has therefore become one of the cornerstones of IPA diagnostics. Brochoalveolar lavage (BAL) Galactomannan (GM) testing is currently the most promising approach for early detection of pulmonary infections by this fungus. However, limitations of GM detection are assay turn-around time, which varies widely between centers (less than a day to several days), and the need for appropriately equipped laboratories that routinely test for this antigen. These limitations are overcome by the Aspergillus Lateral-Flow Device (LFD), a novel point-of-care (POC) test for IPA diagnosis developed by Dr Thornton at the University of Exeter, UK. This simple, rapid (15 min), single-use test can be performed in rudimentary facilities using BAL specimens. In a retrospective single centre study we have recently evaluated the LFD test in 39 BAL samples from hematologic malignancy patients and solid organ transplant recipients. Sensitivities and specificities of BAL LFD tests for probable IPA were 100% and 81%, respectively. Galactomannan levels in cases with negative LFD were significantly lower than in patients with positive LFD (P <0.0001). We concluded that the LFD test of BAL specimens is performed easily and provides accurate and rapidly available results. Therefore, this new point-of-care test may be a very promising diagnostic approach for detecting IPA in BAL specimens from haematological malignancy and SOT patients. For routine clinical use, however, multicenter studies with larger sample sizes also from other patient collectives are necessary. In this multicenter study we will evaluate the LFD test in BAL samples. Study Objectives Primary Objectives To evaluate the Lateral Flow Device test, a rapid (15 min), point-of-care test for IPA diagnosis using bronchoalveolar lavage (BAL) fluids from patients at risk for IPA. Secondary Objective To evaluate the potential of BAL Lateral Flow Device test for prognosis in patients with IPA. Study Design This is a prospective multi-center study conducted in three centers in Austria (Graz, Vienna and Innsbruck) and one centre in Germany (Mannheim). In order to meet the objectives an estimated number of 300 BAL samples from patients at risk for IPA (50 to 100 per centre) will be included in the study cohort. The Lateral Flow Device test will be performed prospectively in BAL samples from the patients and results will be compared to GM results, PCR findings, clinical/radiological findings as well as conventional culture results. In addition, retrospective testing of BAL samples that were previously routinely tested for GM will be performed in up to three participating centers (Graz, Innsbruck and Mannheim) to ensure to reach the proposed number of 300 BAL samples. The treating clinicians will not be informed about BAL Lateral Flow Device test results and the test will therefore have no impact on patient management / treatment decisions.

OPTIFIL is a pilot prospective multicenter study based over the hypothesis that the normalization of the functional imaging 18F-FDG-PET/CT during the Invasive pulmonary aspergillosis (IPA) could occur earlier than that of conventional imaging. This study evaluates the therapeutic response through a systematic 18F-FDG-PET/CT at week 6. The latter response will be correlated with the kinetics of selected biomarkers including antigens (galactomannan, β-D glucans), circulating Aspergillus DNA and anti-Aspergillus host response markers in addition to the conventional imaging tools obtained at weeks 6 and 12.

Background: Fungal infections of the lung (pneumonia) can be caused by molds, such as Aspergillus and Zygomycetes, but these causes are often difficult for a doctor to diagnose. Early and accurate diagnosis of these infections can help doctors to select the correct medicines for proper treatment. A number of methods are used to diagnose fungal pneumonia. Ones that are commonly used in clinical practice include radiographic imaging (chest X-rays and computed tomography (CT) scans), blood tests, and cultures taken from fluid from the lungs (broncho-alveolar lavage (BAL) fluid). Other new methods may improve the diagnosis of fungal pneumonias. These methods include tests that can detect DNA from the fungal germ in blood and BAL fluid of some patients with these infections. Objectives: To help develop better and more accurate methods of diagnosing fungal lung infections. To detect fungal DNA and chemicals in the bloodstream and BAL fluid of immunocompromised patients with pneumonia. Eligibility: - Immunocompromised patients who are currently enrolled in another NIH protocol and who have a CT scan that shows a possible fungal infection of the lung. Design: Researchers will review patients' existing medical records and CT scans, and current pneumonia treatment plans. Patients will provide blood and BAL samples for the duration of their treatment for pneumonia, as required by researchers. Additional CT scans will not be performed, except as part of existing treatment plans.

The purpose of this study is to determine whether inhalation with aerosolized amphoterin B 10mg/d is more effective than aerosolized amphoterin B 2mg/d to reduce the incidence of invasive pulmonary aspergillosis.

A standard treatment protocol for invasive aspergillosis (IA) will be implemented in several academic hematology centers in the Netherlands in which a diagnostic test demonstrating azole resistance by multiplex real-time polymerase chain reaction will guide the choice of appropriate antifungal treatment. Objectives: Improve the outcome of patients infected with azole resistant A. fumigatus by the early detection of Resistance Associated Mutations (RAMs) and with this the earlier initiation of the most appropriate therapy. Monitor the prevalence of invasive aspergillosis due to strains carrying the TR34/L98H or the TR46/T289A/Y121F resistance associated mutations in the Netherlands.

Invasive pulmonary aspergillosis (IPA) is difficult to diagnose and remains a cause of high morbidity and mortality in critically ill patients in the ICU. Accepted diagnostic protocols for haemato-oncological patients are not applicable for critically ill patients in ICUs. Definitive discrimination between aspergillic colonisation and IPA often depends on the clinical experience of the treating physician, evaluating clinical signs, co-morbidities, and course of the disease. Life saving treatment with the first line antimycotic Voriconazol (Vfend®) can only be initiated after diagnosis of IPA. In this prospective clinical trial the investigators aim to structure, optimize and fast track the diagnostic pathway of IPA in critically ill patients treated in our ICU-department.