Goes

Researchers are investigating the effects of PKN605, an oral medication, on reducing the burden of atrial fibrillation in adults diagnosed with this heart rhythm disorder. This Phase 2, randomized, placebo-controlled, and double-blinded study aims to evaluate how well PKN605 works, as well as its safety, tolerability, and how the body processes the drug. Participants must have a history of atrial fibrillation or flutter and meet certain clinical criteria for inclusion. The study begins with a screening period lasting up to 90 days to determine eligibility. After this, participants are randomly assigned to receive either PKN605 or a matching placebo. The treatment phase lasts 24 weeks, during which participants visit the clinic about once a month. Atrial fibrillation is closely monitored throughout the study using various ECG devices. Approximately one month after the treatment ends, a final safety follow-up visit is conducted. Participants will be involved in regular clinic visits for assessments, including ECG evaluations to measure atrial fibrillation burden. Researchers will track how much time participants spend in atrial fibrillation using ECG patch monitors over 24 weeks. Safety and tolerability are also monitored throughout the study. The total participation time includes the screening, treatment, and follow-up phases, providing comprehensive data on the effects and safety of PKN605.

This trial studies men with low-volume, hormone-sensitive metastatic prostate cancer to evaluate if a shorter treatment duration with androgen receptor pathway inhibitors (ARPIs) like Apalutamide or Enzalutamide is as effective as continuous therapy. The purpose is to see if stopping ARPI treatment after 12 months, with the option to restart if the cancer progresses, can reduce side effects and costs without worsening outcomes. This is a Phase 3 randomized nationwide study focusing on patients with low-volume metastatic disease confirmed by imaging and clinical assessment. Participants will receive androgen deprivation therapy (ADT) combined with either continuous ARPI treatment or ARPI treatment stopped at 12 months. Those who stop ARPI after 12 months may restart treatment if their PSA levels rise, confirmed by a second test at least 4 weeks later. The study compares these two approaches to understand if shorter ARPI use is non-inferior to continuous use, aiming to reduce treatment toxicity while maintaining disease control. Participants will be followed for up to 6 years, with clinical progression-free survival as the main outcome. Researchers will monitor time from study inclusion to disease progression or treatment end. Patients will undergo regular assessments including PSA testing and clinical evaluations to track disease status. Safety and treatment effects will be closely observed throughout the study period, which includes up to 5 years of active follow-up after randomization.

Patients in the Prospective Dutch ColoRectal Cancer cohort (PLCRC) with non-metastatic colon cancer that gave consent for additional blood withdrawals are enrolled in the observational PLCRC-MEDOCC substudy. In this study, blood is collected before surgery, after surgery and during follow-up. Within PLCRC-MEDOCC, patients with stage II colon cancer that are not considered to have an indication for adjuvant chemotherapy, can be included in the MEDOCC-CrEATE subcohort under the condition that they gave informed consent in PLCRC for biobanking of tissue and for future studies (Trial within Cohorts design). Patients included in MEDOCC-CrEATE will be randomized 1:1 to the (A) ctDNA-based treatment group versus (B) the standard of care group. A total of 1320 patients will be randomized. Patients randomized to the ctDNA-based treatment group will have their post-surgery samples analysed directly after informed consent for MEDOCC-CrEATE. All patients with detectable ctDNA will be offered adjuvant chemotherapy (3 months CAPOX). Patients with undetectable ctDNA will receive routine follow-up at the surgical department. The aim of this Trial within Cohorts study is to investigate how many patients with detectable ctDNA after surgery start with adjuvant chemotherapy.

This research focuses on patients with metastatic breast cancer who experience oligoprogression, meaning a small number of cancer lesions grow while on palliative systemic treatment. The study evaluates the effects of continuing the same systemic therapy after applying local ablative therapy (LAT) to target these progressing lesions. LAT may include stereotactic ablative radiotherapy (SABR), surgery, or radiofrequency ablation (RFA). This is a Phase 2 trial involving patients with invasive breast cancer who have stable or responding disease for at least six months under systemic treatment. The treatment involves local ablative therapy aimed at one or two metastatic lesions that show progression in size or metabolic activity and are suitable for removal or destruction by surgery, radiotherapy, or radiofrequency ablation. Patients continue their existing systemic therapy, which might be endocrine, targeted, chemotherapy, or immune-checkpoint blockade. The procedure targets lesions confirmed by specific imaging techniques before and after the LAT. The intention is to locally obliterate the progressing lesions while maintaining systemic treatment. Participants will undergo radiological imaging, including FDG-PET-CT scans, before and after LAT to confirm oligoprogression and treatment effect. Researchers will monitor the number of patients free of disease progression at six months. Patients must be closely followed for treatment response, safety, and compliance. The study includes adults aged 18 and older with good performance status who have agreed to participate by signing informed consent. The total duration includes initial imaging, local therapy, and follow-up assessments at six months to evaluate outcomes.

Researchers are evaluating chemotherapy dosing strategies for older patients aged 70 years and above who have metastatic colorectal cancer and are candidates for palliative chemotherapy. This phase III, open-label, randomized controlled trial aims to compare upfront dose-reduced chemotherapy with standard full-dose chemotherapy to see if the reduced dose is not worse in terms of progression-free survival (PFS). The study also examines secondary outcomes including severe toxicity, quality of life, physical function, overall survival, treatment cycles, dose reductions, hospital admissions, cumulative dosage, and cost-effectiveness. Participants are classified based on their risk of chemotherapy toxicity using the Geriatric 8 (G8) questionnaire. Those at low risk are randomized to receive either full-dose or 25% dose-reduced doublet chemotherapy (a fluoropyrimidine combined with oxaliplatin). Patients at high risk receive either full-dose or dose-reduced monotherapy with a fluoropyrimidine. Targeted treatments like bevacizumab or EGFR inhibitors may be added. Dose adjustments are made for moderate kidney impairment. Treatments are given on schedules involving oral and intravenous chemotherapy drugs administered every 2 to 3 weeks. During the study, participants undergo assessments including clinical evaluations, laboratory tests to monitor blood counts and organ function, and questionnaires for quality of life and physical functioning. Progression-free survival is tracked for at least one year after randomization. Researchers closely monitor treatment toxicity, hospitalizations, dose modifications, and survival. The total planned enrollment is 587 patients, with follow-up for safety and effectiveness throughout the treatment period.

Researchers are investigating whether the medicine vicadrostat, when taken together with empagliflozin, can lower the risk of heart-related problems in adults who have type 2 diabetes, high blood pressure, and cardiovascular disease but no history of heart failure. This study is a Phase III trial that compares the effects of vicadrostat plus empagliflozin to a placebo plus empagliflozin in people with these conditions. Participants are randomly assigned to one of two groups: one group takes vicadrostat and empagliflozin tablets, and the other group takes placebo tablets that look like vicadrostat along with empagliflozin. All participants take one tablet daily for a period ranging from two and a half years up to four years and three months. Throughout the study, participants continue their usual medications for diabetes, high blood pressure, and cardiovascular disease. During up to 51 months of participation, participants visit the study site regularly where doctors collect health information and blood samples. Researchers track when participants experience cardiovascular events such as heart-related deaths or heart failure events. The study also monitors participants’ overall health and any side effects they may experience to assess the safety and effects of the treatments.

Researchers are evaluating the effectiveness and cost-effectiveness of microprocessor-controlled knees (MPKs) compared to conventional mechanical knees (CMKs) in adults with lower limb amputation. The study focuses on walking distance as the primary outcome, along with other aspects of body function, activity, and participation. This observational study takes place within the standard healthcare system in the Netherlands and aims to provide a comprehensive understanding of how these prosthetic knees impact users' daily lives. Participants will first be assessed using their own conventional mechanical knee. Then, they will receive a microprocessor-controlled knee and undergo a six-week trial, including twice-weekly 30-minute physical therapy sessions. After the trial, participants switch back to their conventional knee for four weeks before repeating performance tests. Those who received the MPK will have a final follow-up assessment nine months later. This design allows comparison at multiple time points: baseline, after the trial, after returning to the original knee, and long-term follow-up. During four visits over one year, participants perform physical tests such as the 6-minute walking test and Timed Up and Go test. They also complete questionnaires on cost, balance confidence, rehabilitation participation, physical activity, and prosthesis evaluation. Additionally, participants wear an activity monitor for seven consecutive days to track real-life movement. These comprehensive assessments help researchers measure walking ability, prosthesis use, and quality of life while monitoring safety and long-term outcomes.

Researchers are evaluating the use of mifepristone 50 mg taken once a week as a contraceptive for women aged 18 to 35. This phase III study aims to confirm that the chance of pregnancy while using this contraceptive is very low and to demonstrate that mifepristone is safe. Since mifepristone does not contain hormones like estrogens or progestogens, it is expected to have fewer side effects than common hormonal contraceptives and to be better tolerated by users. Participants will take one oral tablet of mifepristone 50 mg once a week for 12 months. This study is open-label and multi-center, focusing on safety, effectiveness, and user acceptability of this weekly pill. The research will assess outcomes such as the overall pregnancy rate measured by the Pearl Index over 12 months and method failure rates, along with safety evaluations at 3, 6, and 12 months. During the study, participants will attend scheduled visits and are asked to maintain a daily diary via smartphone or computer and complete five online questionnaires. Researchers will monitor contraceptive adherence, side effects, and health status through these diaries and visits. The study will also collect medical data if complications or pregnancy occur, aiming to provide a comprehensive understanding of the contraceptive's performance and user experience over one year.

Researchers are investigating the treatment of multiple myeloma using a combination of medicines called daratumumab-lenalidomide-dexamethasone (Dara-Rd). This standard treatment in the Netherlands often suppresses the disease for a long time and continues until it stops being effective. The study aims to find out if stopping treatment temporarily, compared to continuing it without breaks, can improve quality of life by reducing side effects and allowing recovery from toxicity, without reducing survival time. The study involves patients who have completed 12 cycles of Dara-Rd treatment and have responded with at least a partial response without biochemical progression. These patients will be randomly assigned to either continue Dara-Rd treatment continuously or take a treatment-free interval. The medications involved include daratumumab injections, lenalidomide capsules, and dexamethasone. Reduced dosing of lenalidomide is allowed but not below 5 mg, and prior dexamethasone dose changes are permitted. The trial is a nationwide, open-label, randomized Phase III study. Participants will be followed for up to approximately 57 months to compare event-free survival and up to 69 months to compare progression-free survival after randomization. Researchers will monitor disease status, side effects, and overall health during this time. Patients must provide informed consent and will undergo regular assessments to evaluate the impact of continuous versus interrupted therapy on their disease and quality of life.

Researchers are evaluating follow-up care schedules after total hip or knee replacement surgery in adults aged 50 and older. The study aims to determine if reducing routine follow-up visits, specifically the 1-year appointment, is safe and effective compared to standard care. The goal is to potentially lower the number of unnecessary hospital visits and reduce the burden on patients, caregivers, and healthcare professionals, while revising current clinical guidelines accordingly. Participants receive one of two follow-up care plans: Routine Follow-Up (RFU), which includes scheduled X-rays and clinical visits at 3 months and 1 year after surgery; or Check-Up on Demand (COD), which involves a scheduled visit at 3 months and an additional 1-year visit only if requested by the patient or healthcare provider. This study is part of a larger trial consisting of three work packages, with this segment focusing on follow-up during the first year after surgery. During the study, participants' physical function is assessed using PROMIS Physical Function measures before surgery and at 3, 12, 15, 18, and 24 months post-surgery. Researchers also track the number of clinical visits and X-rays from surgery until 24 months later. Patients complete questionnaires and clinical evaluations, with ongoing monitoring to ensure safety and capture any additional follow-up visits as needed.