Roosendaal

Researchers are evaluating the safety and effects of a new medicine called NNC0487-0111 in people who have Heart Failure with preserved Ejection Fraction HFpEF or Heart Failure with mildly reduced Ejection Fraction HFmrEF and excess body weight. This phase 3 clinical trial aims to find out if NNC0487-0111 is safe and effective for treating these conditions compared to a placebo. Participants have HFpEF or HFmrEF and a body mass index of 30 or above. The study is sponsored by Novo Nordisk AS and uses a randomized, quadruple-masked design. Participants will receive either NNC0487-0111 or a matching placebo by injection under the skin once a week. The NNC0487-0111 is given in increasing doses over time. The study is parallel in design, meaning participants are randomly assigned to one of the two groups and receive that treatment throughout the trial. This treatment period extends for up to about 165 weeks. The study evaluates the time to certain heart failure events, hospitalizations, cardiovascular deaths, and other major cardiovascular events. During the study, participants will be monitored regularly to assess heart failure outcomes and kidney function, as well as quality of life using questionnaires like the Kansas City Cardiomyopathy Questionnaire. Safety and effectiveness are assessed through hospital visits, heart failure event tracking, and blood tests including kidney function and blood sugar levels. The total participation spans over three years, with ongoing evaluations to measure the time to heart failure events and cardiovascular outcomes. Participants receive close medical monitoring throughout the study period.

Researchers are evaluating the addition of Saruparib AZD5305 to standard radiation therapy RT and androgen deprivation therapy ADT for men with high-risk or very high-risk localized or locally advanced prostate cancer who have a BRCA1 or BRCA2 mutation. The study aims to determine if Saruparib improves metastases-free survival compared to placebo when added to these treatments. This phase 3 trial involves approximately 700 adult male participants. Participants are randomly assigned to receive either Saruparib or a matching placebo alongside physicians choice of ADT, with or without abiraterone and prednisoneprednisolone, depending on their cohort. Cohort A includes those receiving RT and continuous ADT, while Cohort B includes participants receiving RT, ADT, and abiraterone. Saruparib and placebo are administered orally. Treatment continues with close monitoring throughout the study. Participants will undergo scans including CT or MRI, bone scans, and PSMA-PET after their planned RT to confirm eligibility and monitor disease status. They will be followed for survival and disease progression for up to approximately 11 years. Researchers will assess metastasis-free survival, overall survival, prostate cancer-specific survival, biochemical recurrence, physical function, and urinary symptoms. Safety and drug levels will also be monitored. An independent committee will review safety and efficacy regularly throughout the trial.

Researchers are evaluating orforglipron to measure its effects on cardiovascular outcomes in adults aged 50 and older who have atherosclerotic cardiovascular disease ASCVD andor chronic kidney disease CKD. This phase 3 study aims to compare orforglipron with a placebo to better understand its impact on major cardiovascular events over about five years. Participants will be randomly assigned to receive either orforglipron orally along with standard care or a placebo orally along with standard care. The study is double-blinded, meaning neither participants nor researchers will know who receives the active drug or placebo during the trial period. During the study, participants will be followed for around five years, with researchers monitoring the time to the first major cardiovascular event and additional outcomes such as cardiovascular and kidney events, changes in kidney function measured by eGFR, and the onset of type 2 diabetes. The study includes regular assessments to track these outcomes and ensure participant safety throughout the long-term follow-up.

Researchers are evaluating a shorter treatment duration with androgen receptor pathway inhibitors ARPIs, specifically Apalutamide or Enzalutamide, in patients with low-volume hormone-sensitive metastatic prostate cancer. This phase 3 clinical trial aims to determine if stopping ARPI therapy after 12 months, with the option to restart if the cancer progresses, is not worse than continuing ARPI treatment. The goal is to reduce side effects and costs while maintaining effective disease control. Participants will be randomly assigned after completing 12 months of ARPI treatment to one of two groups one group will continue androgen deprivation therapy ADT combined with ARPI, while the other will stop ARPI after 12 months but may restart it if a confirmed rise in prostate-specific antigen PSA occurs. The PSA confirmation sample must be taken at least four weeks after the initial rise. Treatment will be monitored closely according to these protocols. During the study, participants will be followed for up to 6 years, including 5 years after randomization to track clinical progression-free survival. Researchers will regularly assess disease status, treatment effects, and possible side effects. The study includes regular visits and monitoring to evaluate how long patients remain free from disease progression while comparing the two treatment approaches.

Researchers are evaluating ziltivekimab, a new medicine not yet approved anywhere, to see if it can help people who were hospitalized due to a heart attack. The study aims to find out if ziltivekimab can reduce the development of heart disease and prevent future heart attacks or strokes. This is a Phase 3 clinical trial comparing ziltivekimab to a placebo in patients with acute myocardial infarction. Participants will receive an initial loading dose of ziltivekimab or matching placebo by injection under the skin as soon as possible after an invasive heart procedure, within 36 hours for STEMI or 48 hours for NSTEMI patients. After the loading dose, they will get monthly injections of the same study medicine for up to two years, in addition to their standard care. During the study, participants will be monitored for major cardiovascular events such as heart attack, stroke, and cardiovascular death. Researchers will also track other heart-related outcomes and safety measures over a period of up to 25 months. The study involves regular visits for injections, assessments, and laboratory tests to evaluate the medicines effects and patient health throughout the trial.

Researchers are evaluating the effect of muvalaplin in lowering cardiovascular risks among adults with elevated lipoproteina who either have atherosclerotic cardiovascular disease or are at risk of a first heart attack or stroke. This phase 3, randomized, double-blind study aims to investigate whether muvalaplin can reduce major adverse cardiovascular events compared to placebo in this high-risk population. Participants are randomly assigned to receive either muvalaplin or a placebo, both given orally. The study is designed with parallel groups and will last about 5.25 years, during which the occurrence of cardiovascular events and changes in lipoproteina levels will be closely monitored. Throughout the study, participants will undergo regular assessments including measurement of lipoproteina levels, monitoring of cardiovascular events such as heart attacks or strokes, and evaluation of healthcare resource use. The primary outcome is the time to first major adverse cardiac event, tracked from baseline until the study ends. Safety and pharmacokinetics of muvalaplin will also be evaluated during the trial period.

Researchers are studying patients with non-metastatic stage II colon cancer who are part of the Dutch ColoRectal Cancer cohort PLCRC and who consented to additional blood samples. The study aims to evaluate how many patients with detectable circulating tumor DNA ctDNA after surgery begin adjuvant chemotherapy. This observational and interventional trial includes patients who do not have a standard indication for chemotherapy and involves a randomized design to compare ctDNA-guided treatment with standard care. Patients are randomly assigned to one of two groups the ctDNA-based treatment group or the standard care group. In the ctDNA group, blood samples taken after surgery are analyzed for ctDNA. Those with detectable ctDNA are offered 3 months of adjuvant chemotherapy using CAPOX a combination of fluoropyrimidine and oxaliplatin. Patients without detectable ctDNA receive routine follow-up care. The standard care group receives routine follow-up without knowledge of their ctDNA results. Participants will have blood collected before surgery, after surgery, and during follow-up. Researchers will monitor who starts chemotherapy within 8 to 12 weeks after surgery and will track recurrence rates, disease-free survival, overall survival, time to recurrence, quality of life, and cost-effectiveness over several years. Follow-up assessments occur up to 10 years, allowing detailed long-term evaluation of treatment impact and patient outcomes.

Researchers are studying whether adjuvant chemotherapy can prevent disease recurrence in adults with high-risk rectal cancer who have detectable circulating tumor DNA ctDNA after surgery. The study aims to determine if this chemotherapy improves disease-free survival compared to standard care. Rectal cancer remains a significant cause of mortality, and while current treatments reduce local recurrence, distant recurrence rates stay high. Identifying patients with residual disease through ctDNA may help target those who might benefit from additional chemotherapy. Participants with detectable ctDNA after surgery will be randomly assigned to receive either standard care or adjuvant chemotherapy consisting of 6 cycles of FOLFOX 5FUfolinic acid and oxaliplatin every 2 weeks or 4 cycles of CAPOX capecitabine and oxaliplatin within 8 to 12 weeks after surgery. The chemotherapy treatment lasts about 3 months. The study is conducted within a prospective colorectal cancer cohort using a randomized controlled design. During the study, participants will have blood samples taken and visits with their physicians before each chemotherapy cycle if assigned to treatment. Researchers will monitor disease-free survival, overall survival, and quality of life using questionnaires over several years. They will also assess the clearance of ctDNA after chemotherapy and study its presence at recurrence. The total follow-up includes up to 2 years for disease recurrence and up to 5 years for survival outcomes.

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 determine which DGB technique is better for total weight loss and managing protein calorie malnutrition. The study involves morbidly obese patients eligible for distalisation surgery, addressing a gap in consensus for optimal surgical approaches after failed RYGB. Participants will be randomly assigned to one of two groups DGB type I, which involves lengthening the biliopancreatic limb by modifying the Roux limb and reattaching it further along the intestine, or DGB type II, which lengthens the alimentary limb by dividing and reattaching the biliopancreatic limb. Both procedures are performed laparoscopically. The trial includes follow-up visits at 1.5, 3, 6, 12, 18, 24, and 36 months after surgery to monitor outcomes. During the study, participants will undergo regular clinical and outpatient assessments including weight measurements, evaluation of protein calorie malnutrition, defecation patterns, nutritional deficiencies, and quality of life questionnaires. Researchers will track weight loss and malnutrition treatment needs primarily at one year post-surgery, with additional secondary outcomes assessed up to three years. Patient satisfaction and eating behavior will also be evaluated throughout the follow-up period. The total participation spans up to three years to thoroughly assess long-term effects and safety.

Researchers are evaluating chemotherapy dosing strategies in older patients aged 70 years and above who have metastatic colorectal cancer and are eligible for first-line palliative chemotherapy. This phase III randomized controlled trial aims to compare upfront dose-reduced chemotherapy with standard full-dose chemotherapy, focusing on progression-free survival PFS. Patients are assessed using the Geriatric 8 G8 questionnaire to determine their risk of chemotherapy toxicity, which guides treatment assignment. The study seeks to balance treatment effectiveness with minimizing toxicity, hospital admissions, and maintaining quality of life QoL and physical functioning. Participants classified as low risk for toxicity G8 score 15 or higher are randomized to receive either doublet chemotherapy a fluoropyrimidine combined with oxaliplatin at full dose or with a 25% dose reduction upfront. Those at high risk G8 score 14 or lower or judged high risk by their oncologist receive fluoropyrimidine monotherapy either at full dose or with a 25% dose reduction. The study also allows the addition of targeted treatments like bevacizumab or EGFR inhibitors. Dose adjustments are made for patients with moderate kidney impairment. Chemotherapy is given orally or intravenously on schedules varying between every two and three weeks, depending on the regimen. Participants will be closely monitored throughout treatment, with assessments including radiological or clinical evaluations for disease progression, quality of life and physical functioning questionnaires at 1, 3, 6, and 12 months, and tracking of chemotherapy toxicity, overall survival, treatment cycles, dose changes, hospital admissions, and cumulative drug dosage. Safety and cost-effectiveness will also be evaluated over an average study duration of eight months and up to one year for some outcomes. The study plans to include 587 patients and will continue until December 2028.