Leiden

Researchers are evaluating a "wait-and-see" approach for patients with rectal cancer who respond completely to neoadjuvant chemoradiotherapy. This study aims to provide both short-term and long-term data on cancer control and patient function when surgery is avoided in good responders. The research also seeks to establish a national network of expert centers to improve organ-preserving care and create a registry to gather more evidence about this treatment strategy. The standard treatment for locally advanced rectal cancer typically involves chemoradiotherapy followed by surgery. In this study, patients who show a complete clinical response after treatment will be observed without immediate surgery under a "wait-and-see" policy. The study is a multicenter prospective observational cohort and implementation study, focusing on patients aged 18 or older who have had a long course of chemoradiotherapy or a short course with a long waiting interval. The main goal is to track disease-free survival without tumor regrowth over two years. Participants will be closely monitored using clinical exams, endoscopy, and advanced MRI scans to confirm their response and detect any regrowth early. Researchers will measure outcomes such as two-year disease-free survival, regrowth rate, local control, overall survival, quality of life, and the ability of centers to provide high-quality organ preservation care. Patients will undergo intensive follow-up to ensure safety and gather comprehensive data on the effects of this less invasive approach over time.

This research aims to improve how urinary tract infections (UTIs) are diagnosed in older adults aged 65 years and above. It focuses on identifying the best cut-off values for individual urine biomarkers including NGAL, IL-6, AZU, TIMP2, and CXCL9, and evaluating their sensitivity, specificity, and predictive values. The study also assesses a urine leukocyte count cut-off and the optimal combination of these biomarkers to enhance UTI diagnosis. Additionally, it examines how biomarker levels relate to symptom duration, complications, UTI recurrence within two months, and hospital stay length, while validating the astrego PA100 device for detecting bacteriuria. Participants will provide a midstream urine sample at the start of the study, collected in a sterile container. This sample will be tested for the presence and levels of the specified biomarkers. Researchers will also measure vital signs such as temperature and blood pressure once at the beginning. Participants will answer questions about their symptoms and overall health at the start and again after eight weeks. Throughout the study, researchers will monitor diagnostic accuracy of individual urine biomarkers and panels at baseline. They will gather data through urine tests, vital sign measurements, and participant questionnaires to evaluate biomarker effectiveness. The total observation period includes an initial assessment and a follow-up after eight weeks to track symptom changes and health outcomes.

Researchers are evaluating treatments for patients with high-risk pulmonary embolism (PE), a serious condition where blood clots block arteries in the lungs. This study compares catheter-directed thrombectomy (CDT), a procedure to remove clots directly, against the standard treatment of full-dose systemic thrombolysis, which dissolves clots using medication but carries risks of major bleeding and stroke. The trial aims to find out if CDT is safer and more effective in reducing death, treatment failure, major bleeding, and stroke within 30 days, and whether it improves recovery and quality of life over one year. Participants will receive either CDT, which involves inserting a catheter through veins to remove clots using approved devices and anticoagulant medication, or standard thrombolytic drugs like Alteplase, Urokinase, or Tenecteplase to dissolve clots. The thrombectomy is performed quickly with specific procedures to remove clots and monitor heart function. Researchers will track outcomes including survival, complications, oxygen needs, time spent in intensive care and hospital, and long-term recovery. Treatment success is defined by improvement in right heart function after the procedure. During the study, participants will be closely monitored for 30 days to assess death, treatment failure, bleeding, and stroke. Researchers will also evaluate oxygen use at 48 hours, length of stay in intensive care and hospital, and patient-reported quality of life up to one year. The study includes multiple centers and collects data to understand safety, effectiveness, and cost over time. Participants will undergo imaging, clinical evaluations, and follow-up assessments as part of the trial.

Researchers are evaluating a new scan called FAPI-PET/CT to detect metastases in patients with advanced gastric cancer. The study aims to find out how well this scan identifies metastases and whether it reduces the burden on patients compared to current methods. Key questions include how often the scan changes treatment plans, such as avoiding unnecessary surgeries or switching to palliative care, and how it affects the diagnostic process with additional biopsies or surgery adjustments. Participants will receive the intravenous drug [18F]-FAPI-74 one hour before undergoing the FAPI-PET/CT scan. This scan is done after initial staging with gastroscopy and a contrast-enhanced CT but before a staging laparoscopy. Based on the scan results, the medical team will decide the next steps, which may include biopsy confirmation of suspect lesions or performing diagnostic laparoscopy if the scan is negative. During the study, participants will have one additional scan lasting about two hours (excluding travel) and complete several questionnaires totaling around four hours. Researchers will track changes in treatment intent for about one year and monitor changes in diagnostic work-up immediately after clinical staging involving FAPI-PET/CT and other diagnostic procedures. Safety and treatment decisions will be closely followed throughout the study period.

This is a first in human, randomized, prospective, single centre, double blind, placebo-controlled study in healthy volunteers. It consists of three separate parts (Part A, B and C) with different study designs. The main objective is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending dose (SAD) (Part A and B) and multiple ascending doses (MAD) (Part C) of IMP761 as assessed by: * Vital signs * Treatment-emergent (serious) adverse events ((S)AEs) * Electrocardiography. * Clinical laboratory tests * Laser speckle contrast imaging (LSCI) * Multispectral skin imaging Part A: SAD study in healthy subjects (cohort 1, 5 subjects) Cohort 1: 5 subjects, single i.v. dose of IMP761 or placebo (3:2). The first 2 subjects will receive IMP761 or placebo (1:1) as sentinel dosing, while the following 3 subjects will receive IMP761 or placebo (2:1). Part B: SAD study in healthy subjects, KLH challenge (cohort 2-8, 60 subjects) Cohort 2-3: 5 subjects, single i.v. dose of IMP761or placebo (4:1). Cohort 4-8: 10 subjects, single i.v. dose of IMP761 or placebo (8:2). Part C: MAD study in healthy subjects (MAD cohort 1-2, 14 subjects) MAD Cohort 1-2: 7 subjects, multiple (three i.v. doses of IMP761 or placebo (5:2). Investigational Medicinal Product (IMP)/placebo administration every 28 days; dose selection to be based on observed pharmacodynamic effects in part B.

Researchers are evaluating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of RO7507062 in adults with systemic lupus erythematosus (SLE). This is a Phase 1, first-in-human study with two parts: Part 1 involves single ascending doses to find the appropriate dose, and Part 2 involves dose escalation using fractionated dosing. Tocilizumab may also be used by investigators if needed to manage cytokine release syndrome during the study. Participants will receive RO7507062 as a subcutaneous injection according to their assigned treatment arm. Tocilizumab solution for infusion may be given intravenously at 8 mg/kg for participants weighing 30 kg or more, or at 12 mg/kg for those under 30 kg if clinically required. The study consists of a dose-finding period followed by a dose escalation period with fractionated doses, with safety evaluations extending through these phases. During the study, participants will be monitored for dose-limiting adverse events from day 1 through day 29 in Part 1 and through the 28-day safety evaluation in Part 2. Adverse events will be tracked for up to approximately 12 months. The study includes assessments of safety, drug levels, and effects on disease activity. Participants will undergo clinical evaluations and laboratory tests throughout their involvement, which includes the treatment and follow-up periods.

Researchers are evaluating the long-term safety and effects of nerandomilast in people with idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF) who have previously completed treatment with nerandomilast in earlier studies. The study aims to understand how well participants tolerate nerandomilast over time, and whether it helps improve lung function, delays symptom worsening, reduces hospital visits, or impacts survival. This is a Phase 3 open-label extension trial. Participants take nerandomilast tablets daily for up to 1 year and 10 months while continuing their usual pulmonary fibrosis treatments. The study follows an open-label design where all participants receive nerandomilast. There are no placebo or comparator groups in this extension phase. Throughout the study, participants regularly visit their doctors for health assessments and lung function tests. Doctors monitor any health problems or side effects experienced during treatment. The main outcome measured is whether participants experience any adverse events up to the final follow-up visit, which occurs at week 99. This close monitoring helps evaluate the long-term safety and potential benefits of nerandomilast in this patient group.

This is a long-term follow-up trial to the post-authorisation efficacy and safety (PAES) trial (trial 20-HMedIdeS-19). The trial will include patients who participated in the PAES trial and were transplanted with a new kidney after treatment with imlifidase (trial drug) or standard of care medication. Imlifidase is a medicine used to prevent the body from rejecting a newly transplanted kidney and is used before transplantation in adults who have antibodies against the donor kidney and are considered 'highly sensitised' based on a positive crossmatch test. The purpose of this follow-up trial is to fulfil requirements from the European Medicines Agency (EMA) to continue to evaluate efficacy (kidney function) and safety (side effects) over time, for the patients who were transplanted with a new kidney in the PAES trial. The patients will be followed for up to 5 years after transplantation in the PAES trial to collect valuable long-term data.

Researchers are conducting a master protocol study called CAMPFIRE to efficiently carry out multiple clinical trials testing new drugs in children and young adults with cancer. This master protocol allows for adding new studies as new cancer drugs become available, focusing on the treatment of measurable or evaluable tumors in participants aged 1 to 39 years. The goal is to evaluate various drugs under a unified research plan to improve treatment options for young cancer patients. The study involves several investigational drugs administered either intravenously or orally, including Ramucirumab, Cyclophosphamide, Vinorelbine, Gemcitabine, Docetaxel, Abemaciclib, Irinotecan, and Temozolomide. Each drug is tested under specific clinical trials within the master protocol, with treatment schedules and dosing tailored to each drug. Participants receive these treatments following standard clinical procedures, with adjustments based on individual study protocols and treatment responses. Participants will be closely monitored throughout the trial, with assessments including performance status evaluations, laboratory tests to check organ and blood function, and pregnancy testing for females of childbearing potential. Researchers will track how many participants receive each treatment during the first four weeks and observe the duration of treatment benefits. Safety evaluations, adherence to contraceptive measures, and recovery from prior therapies are also part of the study monitoring. Participation duration and additional assessments depend on the specific trial and treatment plan assigned.

Researchers are evaluating whether the drugs retatrutide and tirzepatide can prevent major adverse liver outcomes (MALO) in adults with metabolic dysfunction-associated steatotic liver disease (MASLD) who are at high risk. This Phase 3 trial enrolls about 4,500 adults with MASLD identified by non-invasive tests indicating an increased likelihood of developing serious liver problems. The study aims to understand how these treatments might affect liver health over time compared to a placebo. Participants will be randomly assigned to receive either retatrutide, tirzepatide, or a placebo, all given by subcutaneous injection. The study will last approximately 224 weeks, during which participants may attend 25 to 30 clinic visits for monitoring and assessment. After the main study, eligible participants can join an optional 2-year extension where all will receive either retatrutide or tirzepatide regardless of their original group. Throughout the trial, participants’ liver function and disease progression will be closely monitored through various health assessments. Researchers will track the time to the first major adverse liver event as the main outcome. Safety and health status will be evaluated regularly during clinic visits, ensuring thorough observation over the long study period.