Roosendaal

Researchers are evaluating the effectiveness of Saruparib (AZD5305) compared to placebo when added to a standard radiation therapy (RT) and androgen deprivation therapy (ADT) regimen in men with high-risk and very high-risk localized or locally advanced prostate cancer who have a BRCA gene mutation. This phase III study aims to assess whether Saruparib can improve metastasis-free survival in this population. About 700 adult male participants will be randomly assigned to receive either Saruparib or placebo along with ADT. There are two groups: Cohort A includes 400 participants with newly diagnosed high-risk or very high-risk prostate cancer treated with primary RT or with high-risk biochemical recurrence after radical prostatectomy receiving salvage RT. Cohort B includes 300 participants with very high-risk locally advanced prostate cancer receiving primary RT combined with ADT and abiraterone. Saruparib and placebo will be given orally, and standard ADT and abiraterone with prednisone/prednisolone will be administered as per the regimen. Participants will be followed for up to about 93 months to monitor metastasis-free survival and overall safety. Assessments include imaging scans like CT, MRI, bone scans, and PSMA-PET to confirm disease status. The study also monitors organ function, performance status, and treatment adherence. An independent committee will review safety and efficacy data throughout the trial to ensure participant well-being and study integrity.

Researchers are evaluating the effects of the drug orforglipron compared with a placebo on cardiovascular outcomes in adults who have atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD). This is a Phase 3, randomized, double-blind, placebo-controlled study designed to investigate major adverse cardiovascular events over a long period. Participants will receive either orforglipron or a placebo orally. The study is event-driven and will continue until the occurrence of major cardiovascular events or up to about 5 years. The treatments are administered without revealing to participants which group they are in to ensure unbiased results. During the study, participants will be monitored for the time to the first occurrence of a major cardiovascular event. Researchers will collect data from baseline through the end of the study, which lasts approximately 5 years. Regular assessments will help evaluate the safety and effects of the treatments on cardiovascular health in this population.

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.

Researchers are evaluating whether ziltivekimab can help people who were hospitalized due to a heart attack by potentially reducing the development of heart disease and preventing new heart attacks or strokes. This Phase 3 study compares ziltivekimab with a placebo, which is a dummy medicine that has no effect on the body. Both treatments are given by chance, with equal likelihood for participants to receive either ziltivekimab or placebo. Participants will inject the study medicine once a month under the skin in the stomach, thigh, or upper arm. Ziltivekimab is given as an initial loading dose followed by monthly maintenance doses. The placebo group receives a matching injection schedule. The study duration is about two years. During the study, researchers will monitor participants for the time until the first serious heart-related event, including cardiovascular death, non-fatal heart attack, or non-fatal stroke. Participants will be closely observed from the start of randomization up to 25 months. The study includes regular follow-ups to assess safety and effectiveness of the treatments throughout this period.

Researchers are evaluating the effect of muvalaplin on reducing cardiovascular risk in adults with elevated lipoprotein(a) levels who either have atherosclerotic cardiovascular disease or are at risk for a heart attack or stroke. This Phase 3, randomized, double-blind, placebo-controlled study focuses on adults with high Lp(a) levels and prior or potential cardiovascular events. The study aims to assess the time to the first major adverse cardiovascular event over about 5.25 years. Participants will be randomly assigned to receive either muvalaplin or a placebo, both administered orally. The study includes individuals with Lp(a) levels of at least 175 nanomoles per liter who have had a prior cardiovascular event within 10 years or are at risk for a first event due to conditions such as coronary artery disease, carotid stenosis, peripheral artery disease, high coronary artery calcium score, reduced kidney function with diabetes, or other high-risk factors. The treatment period lasts through the study duration, with close monitoring. During the study, participants will be regularly evaluated to track the occurrence of major adverse cardiovascular events, including heart attacks and strokes. Safety assessments will monitor blood pressure, kidney function, and heart failure status among other health indicators. The primary outcome measures the time to the first major cardiovascular event from baseline up to the end of the study, which spans approximately 5.25 years.

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.

Researchers are evaluating two surgical methods of distal gastric bypass (DGB) as revisional surgery for patients who have had insufficient weight loss or weight regain after Roux-en-Y gastric bypass (RYGB). This multicenter randomized controlled trial aims to compare DGB with lengthening of the biliopancreatic limb (BPL) and DGB with extension of the alimentary limb (AL) to find the optimal surgical technique for additional weight loss and to assess the need for treatment of protein calorie malnutrition (PCM). The study involves morbidly obese adults aged 18 to 65 years who have failed to achieve sufficient weight loss following primary RYGB. Participants will be randomly assigned in equal numbers to one of the two surgical groups: DGB type I with lengthening of the BPL, or DGB type II with extended AL. The trial will be conducted across multiple bariatric centers with procedures performed in both clinical and outpatient settings. Follow-up visits will occur at 1.5, 3, 6, 12, 18, 24, and 36 months after surgery to monitor outcomes. During the study, participants will undergo regular assessments including weight measurements and monitoring for protein calorie malnutrition. Researchers will evaluate total weight loss one year after the surgery and the development of PCM requiring treatment. Additional outcomes include weight loss over time, remission of obesity-related conditions, nutritional deficiencies, quality of life, patient satisfaction, morbidity, and mortality. Participants must agree to a follow-up program and complete questionnaires throughout the study period.

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 evaluating two methods of delivering spinal cord stimulation (SCS) electrical charge for patients with Persistent Spinal Pain Syndrome Type 2 (PSPS Type 2), also known as Failed Back Surgery Syndrome. This trial compares active recharge burst stimulation with passive recharge burst stimulation to see if there are differences in pain relief and motivational-emotional aspects of pain. This multicenter randomized clinical trial is conducted in six Dutch hospitals and aims to assess which burst stimulation waveform might better affect patient outcomes. Participants will be randomly assigned to receive either active recharge burst or passive recharge burst spinal cord stimulation. After a successful trial period, patients will be permanently implanted with the assigned neurostimulation device. Active recharge burst uses negative pulses to directly compensate for charge differences, while passive recharge burst uses a recharge pattern that passively balances charge differences. The study involves 96 patients and follows them up at multiple time points over a year after implantation. During the study, patients will complete several assessments including the Pain Catastrophizing Scale (primary outcome measured at 6 months), Numeric Pain Rating Scale, Patient Vigilance and Awareness Questionnaire, Hospital Anxiety and Depression Scale, quality of life questionnaires, Oswestry Disability Index, Patient Global Impression of Change, and painDETECT questionnaires. These are completed at baseline, after the trial period, and at 1, 3, 6, and 12 months post-implantation. The study monitors pain experience, emotional and motivational aspects of pain, and overall quality of life throughout the participation period.

Chemotherapy induced peripheral neuropathy (CIPN) is a common and serious condition affecting up to 40% of patients who undergo chemotherapy, causing painful neuropathic symptoms. This research investigates the effectiveness of closed-loop spinal cord stimulation (CL-SCS) therapy, which is designed to treat painful CIPN by automatically adjusting stimulation levels in real time based on nerve responses. The study aims to assess pain reduction and improvement in quality of life for patients receiving this therapy. The closed-loop SCS system works by stimulating the dorsal column of the spinal cord and measuring nerve response to tailor the stimulation for each pulse delivered. Patients selected for this study will have planned implantation of the Evoke SCS System. The therapy is evaluated over several time points to understand its impact on pain intensity and overall symptom management in patients who have had CIPN for at least 3 months and are post-chemotherapy remission. Participants will be monitored and evaluated at baseline and at 1, 3, 6, and 12 months after the SCS implantation to measure changes in overall pain intensity. Assessments include patient-reported pain scores and quality of life measures, with careful follow-up to track treatment effectiveness and safety. The study requires patients to have persistent pain despite other treatments and includes ongoing data collection to provide comprehensive insights into the therapy's impact over a year.