Leiden

This research aims to improve the diagnosis of urinary tract infections UTI in older adults aged 65 years and above. It focuses on finding the best cut-off values for individual urine biomarkers such as NGAL, IL-6, AZU, TIMP2, and CXCL9, along with assessing the sensitivity, specificity, and predictive values of these markers. The study also seeks to validate urine leukocyte count cut-offs and evaluate the combination of biomarkers for better diagnosis. Additionally, it will explore how biomarker levels relate to symptom duration, complications, recurrence within two months, and hospital stay length. The performance of the astrego PA100 device in detecting bacteriuria will also be validated. Participants will provide a midstream urine sample once at the start of the study, which will be collected in a sterile container for biomarker testing. They will answer questions about their symptoms and general health at the beginning and again after eight weeks. Vital signs, including temperature and blood pressure, will be measured once at the start. This observational study does not involve any treatment but focuses on diagnostic assessments. During the study, participants will be monitored for symptoms and potential complications. Researchers will track symptom duration, hospital stay lengths, and recurrence of UTI over an eight-week period. Diagnostic accuracy of individual biomarkers and their combinations will be evaluated at baseline. The study will also assess the diagnostic performance of the PA100 device for bacteriuria detection. Overall participation involves two assessments and one urine sample collection, spanning about eight weeks from inclusion to follow-up.

Researchers are evaluating treatments for patients with high-risk pulmonary embolism PE, a serious condition that requires immediate clot removal in addition to blood thinners. This trial compares two approaches catheter-directed thrombectomy CDT, a procedure that directly removes clots using a device, versus standard full-dose systemic thrombolysis, which dissolves clots using medication. The study aims to see if CDT can reduce death rates and serious complications better than the usual treatment, while also improving recovery and quality of life over one year. Participants are randomly assigned to one of two groups. One group receives the CDT procedure, where a catheter is guided through veins to the lungs to extract clots using suction, combined with blood thinners during the procedure. The other group receives full-dose systemic thrombolysis using clot-dissolving drugs such as Alteplase, Urokinase, or Tenecteplase. The study is open-label, meaning both patients and doctors know which treatment is given. Researchers will monitor effects at various points, including day 7, day 30, and up to one year after treatment. During the trial, participants undergo evaluations including clinical and hemodynamic assessments to determine treatment success, monitoring of oxygen levels, length of stay in intensive care and hospital, and quality of life questionnaires over a year. The main measure is a combined rate of death, treatment failure, major bleeding, and stroke at 30 days. Secondary outcomes include survival, bleeding events, oxygen use, and long-term functional recovery. Cost-effectiveness of the treatments will also be analyzed after one year.

Researchers are studying a new type of scan called FAPI-PETCT to see how well it detects metastases in patients with advanced gastric cancer. The study aims to find out if this scan can better identify cancer spread, leading to changes in treatment plans such as avoiding unnecessary surgeries or shifting to comfort-focused care. It also evaluates whether the scan causes less burden for patients compared to current methods. Participants will receive the standard care for gastric cancer and undergo one additional FAPI-PETCT scan, where a small amount of 18F-FAPI-74 is given intravenously about 60 minutes before a PETCT scan lasting around 20 minutes. The results from this scan will help doctors decide on further tests or surgery needed. The study monitors changes in diagnosis and treatment decisions based on the scan. During the study, participants will complete questionnaires taking about 4 hours total and spend approximately 2 hours for the extra scan. Researchers will measure outcomes such as changes in treatment intent, diagnostic work-up, scan accuracy, incidental findings, patient burden, quality of life, and safety over about one year. Follow-up includes quality of life assessments and cost evaluations at multiple time points after staging.

Researchers are evaluating new treatments for locally advanced non-small cell lung cancer NSCLC that cannot be surgically removed and has a specific gene mutation called KRAS G12C. This trial aims to find out if the combination of calderasib MK-1084 and durvalumab can help participants live longer without their cancer growing or spreading compared to durvalumab with a placebo after they have completed chemotherapy and radiation therapy. Participants will be randomly assigned to receive either calderasib along with durvalumab or a placebo along with durvalumab. Calderasib is taken by mouth as a tablet, and durvalumab is given as an intravenous infusion. This study is double-blinded, meaning neither the participants nor the researchers know who receives the active drug or placebo. The treatment period will be followed by long-term monitoring. During the study, participants will have various assessments including survival monitoring up to approximately 9 years, evaluations of adverse events, response rates, and quality of life questionnaires. Researchers will also collect tumor tissue samples for biomarker analysis. The main measurement is progression-free survival, checked for up to about 6 years. Participants health and side effects will be closely tracked throughout and after treatment.

Researchers are evaluating the safety and tolerability of a new immunosuppressive antibody called IMP761 in healthy adult volunteers aged 18 to 55 years. This first-in-human, randomized, double-blind, placebo-controlled trial aims to determine if single and multiple doses of IMP761 are safe by monitoring vital signs, adverse events, electrocardiography, and laboratory tests. Part B also explores how IMP761 affects the immune response triggered by keyhole limpet haemocyanin KLH. The study consists of three parts Part A and B involve single ascending doses of IMP761 or placebo given intravenously, with Part B including KLH immunization and challenge. Part C involves multiple intravenous doses administered every 28 days for three doses. Participants will receive either IMP761 or a matching placebo during a 4-day in-clinic stay followed by several follow-up visits. The dose and schedule depend on findings from earlier parts of the study. Participants will be closely monitored throughout the study, which lasts up to 103 days from the first dose. Assessments include vital signs, adverse event tracking, electrocardiograms, clinical laboratory tests, laser speckle contrast imaging, and multispectral skin imaging. Researchers will measure pharmacokinetics and pharmacodynamics, and monitor safety laboratory results. The study includes detailed follow-up visits to evaluate any safety concerns and immune responses.

Researchers are studying people with idiopathic pulmonary fibrosis IPF or progressive pulmonary fibrosis PPF who have previously taken nerandomilast in another study. The aim is to assess how well patients tolerate long-term treatment with nerandomilast and to evaluate whether it improves lung function and delays worsening symptoms, hospital visits, or death. This open-label extension trial is sponsored by Boehringer Ingelheim and focuses on treatment over an extended period. Participants take nerandomilast tablets for up to 1 year and 10 months while continuing their usual pulmonary fibrosis treatments. The study involves a single treatment group receiving the drug, and no placebo or comparison groups. Regular visits with doctors help monitor health and collect data during this extended treatment phase. Throughout the study, participants undergo regular lung function tests and health assessments to track any adverse events and changes in lung capacity. The main outcome measured is the occurrence of any adverse events for up to about 99 weeks. Secondary outcomes include changes in forced vital capacity and time to worsening of disease symptoms or hospitalization. The study includes ongoing safety monitoring with a total participation time of up to nearly two years.

Researchers are conducting a master protocol trial designed to efficiently study several different drugs for children and young adults with various types of cancer. This approach allows multiple clinical trials under one common research plan, with each trial focusing on specific cancers like desmoplastic small round cell tumor, synovial sarcoma, and Ewings sarcoma. New drug studies may be added over time as new treatments emerge. Participation depends on how long the treatment benefits last. The study evaluates combinations of drugs given in cycles, including intravenous and oral medicines such as ramucirumab, cyclophosphamide, vinorelbine, gemcitabine, docetaxel, abemaciclib, irinotecan, and temozolomide. Different treatment groups receive specific drug combinations tailored to the cancer type, with treatment cycles lasting 21 or 28 days depending on the regimen. Each group is randomized to receive either an experimental drug combination or an active comparator without any blinding. Participants will be involved from screening through treatment and monitored regularly. Researchers will assess how many participants are assigned to each specific intervention plan within the first four weeks and track treatment effects. Participants must have measurable or evaluable disease, adequate organ function, and meet performance status criteria. Female participants of childbearing potential undergo pregnancy testing and must use contraception during and after treatment. Safety, adherence, and side effects are carefully monitored throughout the study, which is expected to continue until 2027.

This research aims to compare two different weekly doses of Alpha1-Proteinase Inhibitor given by injection under the skin with the standard doses given through a vein in adults with Alpha-1 Antitrypsin Deficiency. The trial focuses on understanding how the body processes the medicine and evaluates how safe and tolerable the different weekly doses are. Both study doctors and participants know which treatment is being given during this open-label study. Participants will be randomly assigned to one of two treatment groups. One group receives 8 weeks of intravenous treatment with 60 mgkgweek Liquid Alpha1-PI followed by 8 weeks of subcutaneous treatment with 90 mgkgweek Alpha-1 15%. The other group receives 8 weeks of intravenous treatment with 120 mgkgweek Liquid Alpha1-PI followed by 8 weeks of subcutaneous treatment with 180 mgkgweek Alpha-1 15%. The study uses a parallel design to evaluate these dosing regimens. During the study, participants will undergo assessments to measure the steady-state exposure of the medicine over weekly dosing intervals and trough levels at specified weeks. Safety and tolerability will be monitored closely throughout. The study lasts about 16 weeks of active treatment, with visits scheduled to collect blood samples and monitor health status. The main outcome is the measurement of the medicines activity over time to understand how different doses are processed by the body.

Researchers are evaluating the effects of ALN-APP on disease progression in adults with sporadic Cerebral Amyloid Angiopathy sCAA and Dutch-type Cerebral Amyloid Angiopathy D-CAA. This Phase 2 study aims to assess the safety, tolerability, and pharmacodynamics of ALN-APP in these patient groups. The study is sponsored by Alnylam Pharmaceuticals and includes a randomized, double-blind, placebo-controlled design. Participants will receive multiple doses of ALN-APP or placebo administered intrathecally during a 24-month double-blind treatment period. Those who continue into an optional 18-month open-label extension will receive ALN-APP. The study involves two main periods the initial double-blind treatment phase followed by an optional open-label extension. During the study, participants will undergo brain MRIs to measure new cerebral microbleeds and other brain changes. Researchers will also assess cerebrovascular vasoreactivity using functional MRI and measure amyloid precursor protein levels in cerebrospinal fluid. Safety and adverse events will be monitored throughout the up to 50 months of participation, which includes screening, treatment, and safety follow-up.

Researchers are evaluating intravenous brincidofovir IV BCV compared to intravenous cidofovir IV CDV for treating adenovirus infection in children and adults who have received allogeneic hematopoietic cell transplants allo-HCT. This Phase 3, multi-center, randomized, open-label study focuses on patients with adenovirus viremia, aiming to assess the effectiveness of these treatments in clearing the virus. The study uses a virologic response-driven approach to determine treatment duration, following ECIL guidelines for high-risk patients. Participants will be randomly assigned to receive either IV BCV or IV CDV. Treatment will continue until adenovirus DNA in plasma is undetectable for two consecutive tests spaced 7 days apart or until a maximum of 12 weeks of therapy is reached, whichever occurs first. Subjects who clear the virus may stop treatment but can be retreated with their assigned drug if adenovirus viremia recurs at defined levels. The study prohibits switching between the two drugs. Safety will be monitored by an independent board during enrollment. Throughout the study, participants will be assessed weekly until the end of treatment, with additional evaluations at 4 weeks after the last dose and at 12 and 24 weeks post-randomization. Researchers will collect plasma samples to measure drug concentrations and monitor viral response and safety. All participants will be followed for a total of 24 weeks regardless of treatment duration, ensuring comprehensive monitoring of efficacy and safety during and after therapy.