Electrophysiology

The purpose of this study is to establish the safety and effectiveness of pulsed field ablation as a first-line ablation treatment for subjects with persistent atrial fibrillation as compared to subjects who received an initial treatment with anti-arrhythmic drugs.

A clinical trial of exercise-similar heart rate acceleration delivered via cardiac pacing vs. sham intervention in subjects at rest will be performed. The study population comprises subjects with guideline-directed medically managed severe left ventricular dysfunction due to ischemic or non-ischemic cardiomyopathy and an existing implantable cardioverter defibrillator or biventricular implantable cardioverter defibrillator. The purpose of the study is to understand how the heart rate pattern of exercise contributes to the considerable cardiac conditioning effects of exercise and estimate whether the pacing approach may have translational clinical applicability. Fifty-two subjects will be randomized, single-blinded, to either the pacing intervention or a sham intervention which they will receive once daily, 3 days/week for 6 weeks. Baseline symptoms and clinical test results will be compared to the same measures at 2 weeks, 4 weeks and 6 weeks of intervention/sham and at 3 months and one-year post-intervention. The primary endpoint will be the change in left ventricular ejection fraction from baseline in intervention vs. sham groups (mixed effects linear regression with time and treatment arm as fixed effects and pre-specified covariates of sex and cardiomyopathy type as random effects). Secondary endpoints will include changes in quality of life, 6-minute walk distance, cardiopulmonary exercise test (CPET) measures, daily activity and major adverse cardiac events (MACE) at 3 and 12 months between pacing and sham groups. A "dose-response" analysis of outcomes at 2, 4, and 6 weeks of the intervention vs. sham compared with baseline will be performed.

ASP2074 is a potential new treatment for people with certain solid tumors. Before ASP2074 is available as a treatment, the researchers need to understand how it is processed by and acts upon the body. This information will help find a suitable dose and check for potential medical problems from the treatment. People in this study will be adults with metastatic or locally advanced solid tumors. Metastatic means the cancer has spread to other parts of the body. They will have been previously treated with all available standard therapies and they may no longer be benefitting from further treatment. There are 2 main aims of this study. The first is to learn if people with certain solid tumors have any medical problems after receiving different doses of ASP2074. The second is to find a suitable dose of ASP2074 to use in future studies. This study will be in 2 parts. In Part 1, different small groups of people will receive lower or higher doses of ASP2074. Any medical problems will be recorded at each dose. This is done to find suitable doses of ASP2074 to use in Part 2 of the study. The first group will receive the lowest dose of ASP2074. A medical expert panel will check the results from this group and decide if the next group can receive a higher dose of ASP2074. The panel will do this for each group until all groups have taken ASP2074 or until suitable doses have been selected for Part 2. In Part 2, other different small groups of people will receive ASP2074 with the most suitable doses worked out from Part 1. This will help find a more accurate dose of ASP2074 to use in future studies. ASP2074 will be given as an infusion on the first day of each treatment cycle. The people in this study will have treatment cycles until: they have medical problems from the treatment; their cancer gets worse; they start other cancer treatment; they ask to stop treatment; or they do not come back for treatment. People will visit the clinic on certain days during their treatment, with extra visits during the first 2 cycles of treatment. During these visits, the study doctors will check for any medical problems from ASP2074. At some visits, other checks will include a medical examination, laboratory tests and vital signs. Vital signs include temperature, pulse, and blood pressure. Also, blood and urine samples will be taken. Electrocardiograms will be done to check the heart rhythm during the study. Tumor samples will be taken during certain visits before treatment begins, during treatment, and when treatment has finished. People will visit the clinic within 7 days after stopping treatment. The study doctors will check for any medical problems from ASP2074. Other checks will include a medical examination, laboratory tests and vital signs. Then, people may visit the clinic at 30 days after stopping treatment. Thirty and 90 days after the last dose, the study doctors will check for any medical problems from ASP2074. People will have their vital signs checked and have some laboratory tests. After this, people will continue to visit the clinic every 6 weeks. This is to check the condition of their cancer. They will do this until their cancer is worse, they start other cancer treatment, they ask to leave the study, or they do not come back for treatment. Then, the study doctors will call every 12 weeks for up to 1 year or until that person asks to leave the study, the study is stopped, or the person cannot be reached.

This phase II/III trial tests the safety, side effects, and best dose of the drug cabozantinib in combination with standard chemotherapy, and to compare the effect of adding cabozantinib to standard chemotherapy alone in treating patients with newly diagnosed osteosarcoma. Cabozantinib is in a class of medications called kinase inhibitors which block protein signals affecting new blood vessel formation and the ability to activate growth signaling pathways. This may help slow the growth of tumor cells. The drugs used in standard chemotherapy for this trial are methotrexate, doxorubicin, and cisplatin (MAP). Methotrexate stops cells from making DNA and may kill tumor cells. It is a type of antimetabolite. Doxorubicin is in a class of medications called anthracyclines. It works by slowing or stopping the growth of tumor cells in the body. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Adding cabozantinib to standard chemotherapy may work better in treating newly diagnosed osteosarcoma.

This phase 2 trial will evaluate the effects of EP547 in subjects with cholestatic pruritus due to Primary Biliary Cholangitis (PBC) or Primary Sclerosing Cholangitis (PSC)

This study will evaluate the safety and efficacy of pembrolizumab (MK-3475) versus placebo as adjuvant therapy in participants with hepatocellular carcinoma (HCC) and complete radiological response after surgical resection or local ablation. The primary hypotheses of this study are that adjuvant pembrolizumab is superior to placebo with respect to: 1) recurrence-free survival (RFS) as assessed by blinded independent central review (BICR); and 2) overall survival (OS).

Primary Aim: To determine if apixaban is superior to aspirin for prevention of the composite outcome of any stroke (hemorrhagic or ischemic) or death from any cause in patients with recent ICH and atrial fibrillation (AF). Secondary Aim: To determine if apixaban, compared with aspirin, results in better functional outcomes as measured by the modified Rankin Scale.

To obtain data for the Rhythmia™ Mapping System in conjunction with Boston Scientific Open-Irrigated (OI) Catheters for ablation of Paroxysmal Atrial Fibrillation (PAF) according to current international and local guidelines. Primary objective: To assess acute and long-term outcomes for the Rhythmia Mapping System in conjunction with Boston Scientific Open-Irrigated Ablation Catheters to treat de novo Paroxysmal Atrial Fibrillation. De Novo PAF is defined as subjects undergoing first ablation procedure for PAF with no prior left atrial ablation (RF, Cryo, Surgical).