Weinheim

Researchers are evaluating whether using an automated Carbon Dioxide CO2 injection system during infrainguinal peripheral vascular interventions PVI can reduce major adverse kidney events within 90 days in patients at moderately increased risk for contrast-associated acute kidney injury CA-AKI. This Phase 3 randomized controlled trial compares a CO2-based contrast medium sparing strategy to the standard use of iodinated contrast media in patients with peripheral vascular and kidney diseases. Participants are randomly assigned to one of two groups. The intervention group receives PVI using an automated CO2 injection system as the primary contrast agent, with iodinated contrast media available as a backup if image quality is insufficient or if the patient cannot tolerate CO2 angiography. The control group undergoes routine PVI using iodinated contrast media according to local standards, avoiding high-osmolar contrast agents. All patients are followed for up to 12 months after their procedure. During the study, participants undergo the planned PVI procedure with either contrast method. Researchers carefully record the amount and reasons for any iodinated contrast media used in the CO2 group. Patients are monitored for kidney-related outcomes, focusing on major adverse kidney events up to 90 days after the intervention. The trial includes ongoing follow-up assessments to evaluate safety and effectiveness over one year.

Researchers are evaluating the real-world effectiveness, safety, and patient compliance of ribociclib combined with an aromatase inhibitor for adjuvant treatment in patients with hormone receptor-positive, HER2-negative early breast cancer at high risk of recurrence. This observational study also compares ribociclib treatment with abemaciclib plus endocrine therapy and endocrine therapy alone, aiming to better understand treatment decisions and clinical adoption in routine practice. The study is conducted across breast centers and gynecological practices to represent typical healthcare settings. Participants receive treatment based on their physicians clinical judgment without randomization or intervention assignment. The study collects data from patients treated with ribociclib plus aromatase inhibitor with or without luteinizing hormone-releasing hormone LHRH, abemaciclib plus endocrine therapy with or without LHRH, or endocrine therapy alone with or without LHRH. Baseline data and follow-up information on adverse events, quality of life, treatment adherence, and socio-economic factors are gathered over time. During the study, participants undergo assessments including evaluation of invasive disease-free survival up to 36 months, quality of life questionnaires, medication adherence reports, and monitoring of adverse events and treatment changes. Data on reasons for treatment decisions, patient perceptions, and healthcare provider involvement are also collected. The study duration extends up to 39 months to provide a comprehensive overview of treatment impact and patient experience in real-world clinical settings.

Researchers are evaluating AZD0780, an oral PCSK9 inhibitor, in a phase 3, randomized, placebo-controlled study. This trial focuses on patients with established atherosclerotic cardiovascular disease ASCVD or those at high risk for a first ASCVD event. The study aims to assess how AZD0780 compares to placebo in reducing the risk of major adverse cardiovascular events, also known as MACE-PLUS, over the course of the trial. Participants are randomly assigned to receive either oral AZD0780 once daily or a matching placebo once daily. The study continues until a primary analysis censoring date, which may be up to approximately 54 months from randomization. After this, a study closure visit will be conducted as the final visit for each participant. During the study, participants will be regularly monitored for cardiovascular events including heart attacks, strokes, urgent coronary revascularizations, and other related outcomes. Researchers will track the time to first occurrence of these events as the primary outcome. Safety and other secondary outcomes like all-cause mortality will also be assessed. The total participation time can last up to about 54 months, with ongoing evaluations throughout this period.

Researchers are evaluating the efficacy, safety, and tolerability of combining elecoglipron and dapagliflozin compared to each drug alone in adults with type 2 diabetes mellitus T2DM who have not achieved adequate control through lifestyle changes or other glucose-lowering medications. This Phase III study aims to better understand how these treatments work together in managing blood sugar levels in this population. Participants are randomly assigned to one of five groups two groups receive elecoglipron at different dose levels combined with dapagliflozin two groups receive elecoglipron at different dose levels combined with a placebo matching dapagliflozin and one group receives dapagliflozin alone with a placebo matching elecoglipron. All medications are taken orally once daily. The treatment period lasts 40 weeks, during which the effects of the drugs on blood sugar and other health measures will be monitored. Throughout the study, participants will have regular assessments of their blood sugar control, body weight, and blood pressure. Researchers will measure changes in Hemoglobin A1c HbA1c, fasting plasma glucose, and self-monitored blood glucose levels. Other outcomes include weight loss and the need for rescue medication. Safety and tolerability will be closely monitored. Participation in the trial lasts for 40 weeks, during which participants will attend scheduled visits for evaluation and medication monitoring.

Researchers are evaluating the effects of the drug imlunestrant LY3484356 in premenopausal women with early estrogen receptor-positive ER, HER2-negative breast cancer. The study includes two groups one that explores imlunestrant alone or combined with ovarian suppression, and another that studies imlunestrant without ovarian suppression. The trial compares imlunestrants impact on breast cancer cells and ovarian function to tamoxifen, a known treatment. Participants in Cohort 1 will receive imlunestrant orally either alone or with goserelin a drug given by injection to suppress ovarian function for up to 29 days. Some in this group will take tamoxifen orally as a comparator. Cohort 2 participants will take imlunestrant or tamoxifen orally for up to 6 months without ovarian suppression. The study is open-label, randomized, and phase 2, designed to assess treatment effects in parallel groups. During the study, participants will provide tumor samples before and during treatment, and researchers will monitor changes in specific cancer markers like Ki-67, estrogen receptor ER, and progesterone receptor PR expression. They will also track the rate of ovarian cysts up to 180 days. Participants must attend scheduled visits for evaluations, including performance status checks and safety assessments. The trial is expected to continue until December 2029.

Researchers are evaluating the effects of vicadrostat combined with empagliflozin in adults who have type 2 diabetes, high blood pressure, and cardiovascular disease but no history of heart failure. The study aims to assess whether this combination can help reduce cardiovascular risks compared to a placebo with empagliflozin. This Phase III trial involves adults with these conditions who are already receiving treatment for them. Participants are randomly assigned to one of two groups. One group takes vicadrostat and empagliflozin tablets daily, while the other group takes placebo tablets that look like vicadrostat but have no active medicine, alongside empagliflozin. Treatment lasts from two and a half years up to four years and three months. All participants continue their usual medications for diabetes, blood pressure, and heart disease during the study. Throughout the study, lasting up to four years and three months, participants visit the study site regularly for health checks and blood samples. Doctors monitor cardiovascular events and any side effects experienced. The main outcome measured is the time until the first cardiovascular death or heart failure event. Other health indicators like blood pressure and kidney function are also tracked to understand the effects of the treatment combination.

Researchers are evaluating vamifeport in adults with homeostatic iron regulator gene-related hereditary hemochromatosis HFE-HH, a condition characterized by iron overload. This phase 2, multicenter, randomized, placebo-controlled, double-blind study aims to assess the effect of vamifeport on liver iron concentration using magnetic resonance imaging MRI. The study focuses on adults with confirmed HFE-HH and iron overload to explore the potential impact of the treatment. Participants are randomly assigned to receive either a low dose or a high dose of vamifeport, or a placebo, all administered orally twice daily up to 360 days. The study compares these three groups over this treatment period to evaluate the treatments effect on liver iron levels. The study includes careful monitoring and assessment of safety and efficacy throughout the treatment duration. During the trial, participants undergo regular assessments including MRI scans to measure liver iron concentration at baseline and day 360. Safety is monitored by tracking adverse events, laboratory tests, and electrocardiograms up to day 390. Additional evaluations include measurements of transferrin saturation, serum ferritin, joint pain, fatigue, and quality of life questionnaires. Blood samples are collected to measure vamifeport concentrations at specific time points. Participants are followed for a total of about 13 months, including treatment and safety monitoring periods.

Researchers are evaluating elacestrant compared to standard endocrine therapy in patients with estrogen receptor-positive ER and human epidermal growth factor receptor 2-negative HER2- breast cancer who have a relapse detected by circulating tumor DNA ctDNA. This international, multi-center, randomized, open-label phase III trial focuses on patients without distant metastasis who show ctDNA positivity during screening. The study aims to assess whether elacestrant can improve outcomes over the current standard endocrine treatments. The study consists of two phases. First, during the ctDNA screening phase, patients on standard adjuvant endocrine therapy will have plasma samples collected every six months for about 5.7 years to detect ctDNA. Patients who test positive will undergo imaging to confirm no distant metastasis and then be randomized 11 to either continue their current endocrine therapy or receive elacestrant 400 mg orally once daily. Treatment duration depends on prior endocrine therapy length, lasting between 2 to 6 years. Intensive follow-up with ctDNA testing and imaging occurs for up to 3 years after randomization. Participants will be monitored closely with blood tests for ctDNA at weeks 4, 16, and every 16 weeks thereafter, along with yearly mammograms, bone scans, and CT scans every 16 weeks to detect metastases or recurrences. Safety, quality of life, and overall survival are assessed throughout, with follow-up continuing until three years after the last patient enrolls. The primary outcome measured is distant metastasis-free survival at 6.25 years after the first randomization.

Researchers are studying patients with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer who have gBRCA12 mutations. This study aims to evaluate whether adding elacestrant, a new oral estrogen receptor blocker, to the standard olaparib treatment can improve progression-free survival compared to olaparib alone. This is a phase II, multi-center, randomized, open-label study with patients assigned in a 21 ratio to two different treatment groups. Participants randomized to Arm A will receive 600 mg of olaparib daily plus 400 mg of elacestrant daily, while those in Arm B will receive 600 mg of olaparib daily alone. Treatment will continue until disease progression, unacceptable side effects, patient withdrawal, or the study ends. Pre- and perimenopausal women, as well as men, will also receive a GnRH analogue at least two weeks before treatment starts. Dose modifications are provided for managing specific side effects. During the study, blood tests will be done at the start of each treatment cycle, and imaging scans along with quality of life assessments will be performed every three months or if disease progression is suspected. Researchers will measure progression-free survival, overall survival, treatment failure times, response rates, clinical benefit, adverse events, and treatment compliance. Participants may remain in the study for up to 48 months, with an average treatment duration of about 12 months per patient.

Cholangiocarcinoma is a rare and aggressive bile duct tumor with poor outcomes and limited treatment options. Researchers are collecting real-world data on ivosidenib, an IDH1 inhibitor recently approved in Europe for adults with locally advanced or metastatic cholangiocarcinoma carrying an IDH1 R132 mutation who have undergone at least one prior systemic treatment. This observational study aims to evaluate ivosidenibs effectiveness, safety, and impact on quality of life in a broad patient population in Germany. Ivosidenib is given as monotherapy according to the current summary of product characteristics SmPC. The study follows patients receiving ivosidenib under routine clinical care without altering treatment decisions. It will gather data on treatment dosing, modifications, duration, and reasons for stopping treatment. Optional patient-reported outcomes PRO assessments are available for those who can participate in German. Participants are monitored during treatment and follow-up for up to 38 months from first patient in to last patient last visit. The study collects information on progression-free survival, overall survival, adverse events, quality of life related to cholangiocarcinoma, and physician treatment decisions. Data on prior therapies, concomitant medications, and subsequent cancer treatments are also recorded to assess real-world use and safety of ivosidenib.