Safety Harbor

Researchers are evaluating AZD0780, an oral PCSK9 inhibitor, in a phase 3, randomized, placebo-controlled study to see if it can reduce the risk of major adverse cardiovascular events (MACE-PLUS) in adults with established atherosclerotic cardiovascular disease (ASCVD) or those at high risk for a first ASCVD event. The study compares AZD0780 to a placebo and monitors participants from randomization until the primary analysis censoring date, followed by a final study closure visit. Participants will be randomly assigned to receive either oral AZD0780 or an oral placebo once daily. The treatment period lasts until the primary analysis censoring date, after which a study closure visit will occur. The study is event-driven and designed to assess the time to the first major cardiovascular event during treatment. During the study, participants will be closely monitored with various assessments to evaluate cardiovascular outcomes and safety over approximately 54 months. Researchers will track the time to first event of any component of MACE-PLUS and collect data to assess the effect of AZD0780 compared to placebo. The study includes regular visits and evaluations to ensure participant safety and adherence to treatment.

Researchers are investigating the addition of an immunotherapy drug called durvalumab to standard chemotherapy treatment in patients with MammaPrint High 2 Risk (MP2) stage II-III hormone receptor positive, HER2 negative breast cancer. This phase III trial aims to compare the effectiveness of usual chemotherapy alone versus chemotherapy combined with durvalumab. Immunotherapy with durvalumab may help the immune system attack cancer cells and prevent tumor growth and spread, while chemotherapy drugs like paclitaxel, doxorubicin, and cyclophosphamide work to stop cancer cells from growing or dividing. Previous studies suggest patients with an MP2 result might respond better to this combined treatment approach. Participants first undergo MammaPrint testing to confirm MP2 status before randomization into two groups. One group receives paclitaxel intravenously on days 1 and 8 every 14 days for 6 cycles, followed by doxorubicin and cyclophosphamide intravenously on day 1 every 14 days for 4 cycles. The other group receives the same chemotherapy schedule plus durvalumab intravenously over 60 minutes on specified cycles during both chemotherapy phases. Mammography is performed during screening, and optional tissue and blood samples are collected for future studies. Throughout the study, participants are monitored through various assessments including imaging, physical exams, laboratory tests, and quality of life questionnaires focusing on fatigue and physical and mental health. Researchers track breast cancer event-free survival and other outcomes such as treatment side effects and response rates. After completing treatment, patients are followed for up to 10 years or until death to evaluate long-term outcomes and safety.

The goal of this trial is to determine the efficacy of advanced cognitive training for cancer survivors suffering from cancer- and cancer-treatment-related cognitive dysfunction. For millions of cancer survivors, cognitive dysfunction is a prevalent, severe, and persistent problem that has long been associated with poor work-related and health-related outcomes. Evidence suggests that a significant subset of breast cancer survivors (BCS) incur cognitive changes that may persist for years after treatment. Unfortunately, the scientific basis for managing these cognitive changes is extremely limited. Available evidence from pilot studies, including our work, suggests that advanced cognitive training, which is based on the principles of neuroplasticity (ability of brain neurons to re-organize and form new neural networks), may be a viable treatment option. However, previous trials to date have been limited by lack of attention-controlled designs, small samples of BCS, or limited outcome measures. Therefore, to overcome limitations of past studies and build on our pilot results, the purpose of this 2-group, double-blind, randomized controlled trial is to conduct a full-scale efficacy trial to compare advanced cognitive training to attention control in BCS.

Researchers are collecting blood and tissue samples from people with and without cancer to study and evaluate tests that could help detect cancer early. The goal is to create a blinded reference set of samples to validate blood-based tests for early detection of multiple types of cancer, including leukemia, lymphoma, breast, lung, and others. The study also aims to assess how well these tests perform at the time of initial cancer diagnosis, considering different tumor types and cancer stages. Participants complete a baseline questionnaire and provide blood samples at registration and again 12 months later. Those diagnosed with cancer may also provide tissue samples at these times. The study includes patients aged 40 to 75 years, with cancer diagnoses at various stages or individuals without cancer. Special procedures are in place for patients with high suspicion of certain cancers before confirmation. During the study, researchers collect detailed information through questionnaires, blood draws, and tissue sampling to analyze test accuracy. Participants are monitored for up to one year after registration to follow outcomes. The primary measure is providing this blinded set of blood samples to help validate future cancer detection tests, supporting research that could improve early diagnosis and treatment.

This research aims to evaluate how well serum cystatin C works in the early detection of acute kidney injury (AKI) caused by contrast media during imaging procedures. It also compares the accuracy of kidney function estimates based on cystatin C versus those based on creatinine, taking into account patient characteristics. The study focuses on inpatients with chronic kidney disease undergoing CT scans or coronary angiography using isohexol (Omnipaque) contrast. Participants are adults aged 18 and older who need contrast imaging studies and have both pre- and post-contrast measurements available. The study monitors kidney function by measuring the incidence of AKI using serum creatinine compared to serum cystatin C at 24 to 48 hours after contrast exposure and again at 7 to 10 days follow-up. There are no specific investigational treatments given, but kidney function is carefully assessed during this time. During the study, participants will have blood tests taken before and after contrast procedures to measure kidney function markers. Researchers will track changes in these markers to detect AKI early. The main outcome is the rate of AKI detected by the two different blood tests within the 10-day observation period. The study includes careful monitoring for safety and to evaluate the usefulness of cystatin C in clinical practice.

Researchers are evaluating the effects of dalcetrapib, a cholesterol ester transfer protein inhibitor, on cardiovascular risk in people who have recently been hospitalized for acute coronary syndrome (ACS) and have a specific genetic profile (AA genotype). This phase 3, placebo-controlled, randomized, double-blind study focuses on adults aged 45 years and older. Participants must be clinically stable and managed according to guidelines for low-density lipoprotein cholesterol (LDL-C). The study aims to measure the time to the first occurrence of any fatal or non-fatal myocardial infarction over an average follow-up of 30 months. Participants will be randomly assigned to receive either dalcetrapib 300 mg tablets or matching placebo tablets. The study includes a genetic screening phase to confirm the presence of the AA genotype using a specific genotype assay test. Screening and enrollment may start during hospitalization or after discharge, with randomization required within 12 weeks of the ACS event. Follow-up visits will be conducted virtually when possible every 3 months or as clinic visits until the study ends. If a participant stops the study medication early, assessments for study endpoints will continue every 3 months. Throughout the study, participants will undergo medical history reviews, genetic testing, and regular assessments to monitor cardiovascular events. Researchers will collect data on myocardial infarction occurrences as the primary outcome. Safety and adherence will be monitored through scheduled visits, and the study will continue until about 200 participants have experienced a primary event or until a planned interim analysis determines stopping. The total participation duration varies based on event occurrence but involves ongoing follow-up every 3 months after randomization.

Researchers are evaluating if adding adjuvant chemotherapy (ACT) to ovarian function suppression (OFS) plus endocrine therapy (ET) improves invasive breast cancer-free survival (IBCFS) compared to OFS plus ET alone. This Phase III trial focuses on premenopausal women with early-stage breast cancer that is estrogen receptor (ER)-positive, HER2-negative, and has a 21-gene recurrence score between 16-25 for node-negative patients or 0-25 for patients with 1-3 positive nodes. The study addresses the need for better treatment options for younger women diagnosed with this type of breast cancer, as younger age is linked to worse outcomes despite standard therapies. Participants receive one of two treatments: either OFS combined with an aromatase inhibitor (AI) for five years or adjuvant chemotherapy followed by the same OFS plus AI regimen. The specific AI and GnRH agonist used, along with their dosing schedules, are chosen by the investigator, commonly including goserelin, leuprolide, or triptorelin administered monthly or every three months. Bilateral oophorectomy may be used instead of ovarian suppression if preferred. Endocrine therapy beyond five years is at the investigator's discretion. During the trial, participants will be closely monitored for invasive breast cancer-free survival over an 11-year period from randomization. Assessments include clinical evaluations, hormone receptor testing, tumor staging, and genetic recurrence scoring prior to enrollment. Safety and effectiveness data will be collected throughout the study, with particular attention to treatment side effects and long-term outcomes. The trial involves detailed eligibility screening and ongoing follow-up to ensure accurate measurement of the study's primary outcome.

Researchers are evaluating inclisiran, a subcutaneous injection given twice yearly, to see if it can prevent major cardiovascular and limb events in patients undergoing percutaneous coronary or peripheral arterial revascularization. This Phase 4, randomized, double-blind study includes patients with symptomatic coronary artery disease or peripheral artery disease who have recently had successful revascularization procedures. The trial aims to assess the real-world effectiveness of inclisiran alongside usual care in a typical U.S. patient population with atherosclerotic cardiovascular disease. Participants will be randomly assigned to receive either 300 mg inclisiran or a matching placebo by subcutaneous injection on Day 1, Month 3, and then every 6 months thereafter. The first dose is given within 14 days of a successful percutaneous coronary or peripheral endovascular intervention. Both groups will continue to receive standard medical care as directed by their physicians. The study plans to enroll about 6,000 participants and treatment duration may last up to approximately 45 months. During the study, researchers will monitor participants for the occurrence of major adverse cardiovascular events and major adverse limb events for up to about 4 years. Participants will have regular follow-up visits and safety assessments throughout the study period, which is designed to continue until around 2,380 primary events have occurred or at least half the participants have completed 36 months of follow-up. Outcome measures focus on the number of cardiovascular and limb events after the procedures, providing important information on the long-term impact of inclisiran in this patient group.

Researchers are investigating whether observation is as effective as continuing pembrolizumab treatment in patients with early-stage triple-negative breast cancer who achieved a complete response after preoperative chemotherapy combined with pembrolizumab. This phase III trial aims to evaluate recurrence-free survival and quality of life, as well as the value of reducing immunotherapy treatment after surgery in these patients. The study also examines differences in adverse events, overall survival, and financial impacts between treatment approaches. Participants are randomly assigned to one of two groups after completing neoadjuvant chemotherapy with pembrolizumab and surgery. One group receives pembrolizumab intravenously as adjuvant therapy, while the other group undergoes observation without further treatment. Both groups have tumor biopsies and blood samples collected on study and during follow-up. Additional assessments include questionnaires and quality-of-life evaluations. During the study, researchers monitor participants for up to 10 years to measure recurrence-free survival. They assess quality of life using validated tools, track adverse events, and evaluate financial toxicity and work productivity. The study includes tumor tissue analysis, blood sample collection, and patient-reported outcomes to understand the long-term effects and value of treatment de-escalation in breast cancer care.

Researchers are evaluating the long-term reliability and performance of Medtronic cardiac rhythm products, including leads and devices used for pacing, sensing, or defibrillation. The study aims to analyze product survival probabilities to better understand their durability and performance over time. This research includes all Medtronic market-released leads and implantable devices for conditions such as arrhythmia, bradycardia, heart failure, and sinus tachycardia. Participants include those who have been implanted with at least one Medtronic market-released product or those who participated in qualifying Medtronic studies with complete implant and follow-up data. The study monitors these devices from the time of implant, tracking lead-related complications and device performance. If a patient exits the study, passes away, or the device is deactivated, the implant is no longer followed. During the study, researchers collect health information and monitor the devices to assess ongoing performance and complications. Follow-up is essential to confirm device status and ensure accurate data collection. The main outcome measured is lead-related complications for each lead model, with continuous observation from implant until termination due to patient or device status. Participation requires informed consent and authorization for access to health information as per institutional requirements.