Vendargues, France

A Phase III Renal Outcomes and Cardiovascular Mortality Study to Investigate the Efficacy and Safety of Baxdrostat in Combination With Dapagliflozin in Participants With Chronic Kidney Disease and High Blood Pressure

The purpose of this study is to investigate the efficacy, safety, and tolerability of baxdrostat in combination with dapagliflozin, compared with placebo and dapagliflozin, in reducing the risk of the composite of > 50% decline in eGFR, kidney failure, or CV death, in individuals with CKD and HTN. This study consists of a 4-week dapagliflozin Run-in Period for participants untreated with SGLT2i at screening, and a double-blinded period where participants will receive either baxdrostat/dapagliflozin or placebo/dapagliflozin. Site visits will take place at 2-, 4-, 8-, 16-, 34, and 52-weeks following randomisation. Thereafter visits will occur approximately every 4 months. The study closure procedures will be initiated when the predetermined number of primary endpoint events is predicted to have occurred ie, the PACD. All randomised participants including any participants who have prematurely discontinued study intervention will be scheduled for a SCV within a few weeks of the PACD. This period can be extended by the Sponsor. In case of premature discontinuation of blinded study intervention, participants will continue in the study and receive dapagliflozin 10 mg, unless the participant meets dapagliflozin specific discontinuation criteria. If study intervention is temporarily or permanently discontinued, the participant should remain in the study, and it is important that the scheduled study visits (including the PTDV for participants with permanent discontinuation of study intervention) and data collection continue according to the study protocol until the SCV.

Blood Purification for the Treatment of Pathogen Associated Shock

Patients meeting the eligibility criteria will be randomized to receive either treatment with the investigational device (Seraph 100) + 'State of the Art' care versus 'State of the Art' care alone. This study is a multi-center, un-blinded, randomized controlled feasibility trial to evaluate the initial safety and efficacy of Seraph 100 in critically ill patients with pathogen associated shock across 15 US sites. This study will not be done in a blinded fashion from either the patient or caregiver perspective given: 1) the need for invasive, central line placement, and 2) to ensure that limited hospital resources (e.g., hemodialysis machines) are available for patients that require therapy. While the study trial will not be conducted in a blinded fashion, the members of the study team that do the data analysis will be blinded. The target population is adults (18 years old and older) admitted to the ICU with all of the following: - Pathogen associated shock AND - The need for vasopressors at any dose to maintain mean arterial pressure (MAP) ≥ 65 mm Hg despite adequate fluid resuscitation. Study Arms: Patients will be randomized to receive either Arm 1: Seraph 100 treatment plus 'State of the Art' or Arm 2: 'State of the Art' care alone. "State of the Art care" will be defined as the treatment algorithms outlined in the Surviving Sepsis Campaign for the treatment of septic shock, available at https://www.sccm.org/SurvivingSepsisCampaign/Home. Study Randomization and stratification: Patients who qualify will be immediately randomized. The study will randomize patients 2:1 to investigational product plus 'State of the Art' care and 'State of the Art' alone, respectively. Upon randomization, patients will be stratified by age (≥65 and <65). While ideally, the research team would stratify by other variables (to include demographics, causative pathogen, GCS, SOFA, associated organ failure, and pre-existing conditions), given the small number of patients in this trial (particularly in the control group) this is not possible. The Seraph 100 Microbind® Affinity Blood Filter (Seraph 100) manufactured by ExThera Medical Corporation in Martinez, CA. Investigational Treatment Duration for Seraph 100: A sufficient blood flow rate and exposure of the patient's blood to the Seraph 100 adsorption media will optimize the treatment success with a target total filtered blood volume of 100L per day. Based on the target total filtered blood volume of 100L, the average treatment duration and blood flow rates are captured below: Average Blood Flow Rate Treatment Duration 350 ml/min 5 hours 300 ml/min 6 hours 250 ml/min 7 hours 200 ml/min 8 hours - At an average blood flow of 350mL/min, this would translate to almost 5 hours of treatment time; an average of 200mL/min would mean a treatment time of 8 hours. - Treatments will occur daily for up to 4 consecutive days or until all of the following criteria are met: - Vasopressor-free for >24h - MAP≥65 - Treatments will be held if subjects are unable to tolerate extra-corporeal therapy (defined as MAP<65 despite fluids and vasopressors) Patients will be assessed daily while hospitalized as part of routine, standard of care in the ICU. All patients enrolled in this study will undergo clinical efficacy, safety, and laboratory assessments. Blood, urine, and respiratory samples will be obtained at baseline, Day 1 (pre/post treatment) through Day 4, Day 7, and Day 28. Demographic and baseline clinical parameters will be recorded at the time of randomization. Pertinent clinical parameters will be recorded hourly for the first 96 hours, once on day 7, and once on day 28. SOFA scores will be recorded daily for the first 7 days. Outcomes data will be recorded on day 28 and at the time of hospital discharge or death. Patient status will be assessed at 30, 60, and 90 days to include vital signs, physical examination, adverse event evaluation, and a targeted medication review. Survival status will be assessed 90 days after enrollment (if the patient is no longer hospitalized). The first 10 patients randomized to interventional therapy, as well as the first 5 patients randomized to the control group, will undergo additional pharmacokinetic (PK) evaluation of antimicrobial removal by the filter treatment. These first 15 total patients enrolled must also meet all requirements for the main portion of the study. As part of the initial PK study, the Data Safety Monitoring Board (DSMB) will also review safety data after the first 5 device patients consented and treated. Safety and PK data will also be reviewed after the first 10 device patients are consented and treated. If there are significant safety concerns after DSMB review, the sponsor will immediately pause the trial and communicate the information with the FDA. The PK results of the first 10 treatment patients will be reported to FDA for review to confirm the proposed dosing prior to commencing enrollment of the remaining subjects for a total of 60 patients.

A Study of SNP-ACTH (1-39) Gel in Patients With Primary Membranous Nephropathy

This head-to-head, open-label, 2-phase superiority trial compares SNP-ACTH (1-39) Gel to rituximab in the treatment of PMN that commences with an adaptive trial design for dose finding. The trial will be divided into 2 parts: Phase 3a and Phase 3b. Dose finding Phase 3a part of the study will enroll a total of 16 patients randomized to 2 different dose levels of SNP-ACTH (1-39) Gel treatment for 12 months. Dose levels will be: - 8 patients at 3mg SNP-ACTH Gel subcutaneous (sc) injection 3 times per week; - 8 patients at 5mg SNP-ACTH Gel sc injection 3 times per week Data from the Phase 3a part of the study will be assessed at regular intervals (at months 2, 3, 4, 5, 6, 9, 12) and will inform the dose selection for the Phase 3b. The optimal dose will be determined based on a risk/benefit assessment from data obtained from the Phase 3a part of the study, with the earliest assessment being conducted after all patients have completed at least 2 months of therapy. The Phase 3b part of the study will enroll 132 patients randomized 1:1 to either 12 months of 1g Rituximab therapy (2 treatment cycles at month 1 and month 6) or 12 months of SNP-ACTH (1-39) Gel treatment at the dose level determined in the Phase 3a.

Combined Dose-Finding and CV Outcomes Study With CSL300 (Clazakizumab) in Adult Subjects With ESKD Undergoing Dialysis

MILD® Percutaneous Image-Guided Lumbar Decompression: A Medicare Claims Study

In this study the treatment group will include all patients receiving MILD, and the control group will include all patients receiving IPD for the treatment of LSS during the enrollment period. Reoperation and harms data will be studied for the MILD and IPD procedures for a 24-month follow-up period after the index procedure using Medicare claims data. This study is exempt from IRB oversight (Department of Health and Human Services regulations 45 CFR 46) and does not require prior enrollment nor patient consent. The inclusion of the study's NCT number on MILD Medicare claims is required and results in enrollment.

MammaPrint, BluePrint, and Full-genome Data Linked With Clinical Data to Evaluate New Gene EXpression Profiles

The FLEX Registry will include all patients with stage I-III breast cancer who have received MammaPrint and BluePrint testing in any clinical setting. Study arm appendices will specify treatment arm, inclusion criteria, and number of patients needed. Approximately 30,000 patients from 125+ US based institutions will be enrolled. Treatment is at the discretion of the physician adhering to NCCN approved regimens of a recognized alternative. Clinical data will be collected and entered online at the time points listed: patient enrollment, time of treatment, 1 year post-treatment, and 3, 5, and 10 years post diagnosis. Objectives: - Create a large scale, population-based registry of full genome expression data and clinical data to investigate new gene associations with prognostic and/or predictive value - Utilize shared registry infrastructure to examine smaller groups of interest - Generate hypotheses for targeted subset analyses and trials based on full genome data FLEX is an observational (phase IV) study.

RSSearch Patient Registry-Long Term Study of Use of SRS/SBRT

The Registry is designed to help SRS/SBRT (Stereotactic Radiosurgery/Stereotactic Body Radiation Therapy) users to understand utilization of and key treatment outcomes for these treatment approaches. Some of the objectives include: Allow participants to record information about usage of SRS/SBRT in everyday practice, including patient characteristics and disease information, treatment plans and outcomes Provide participants with ready access to data for publication of their own experience and as a tool for establishing collaborations with other participating sites Facilitate quality improvement efforts for individual treatment providers Understand the effectiveness of different treatment plans for different types of lesions, diseases and treatments The Registry tracks select outcomes for each condition treated by SRS/SBRT (for example, PSA for prostate cancer); the Registry also provides individual participants the ability to add additional outcomes for each and any condition of specific interest to their institutions. The Registry is hosted by Vision Tree, Inc who is an independent vendor of electronic registries; they are responsible for HIPAA compliance, including all security mechanisms. Patients will be enrolled prospectively. Some retrospective patient data is likely to be included in order to capture both short and longer term outcomes data.

Connect® Myeloid Disease Registry

This Disease Registry will collect data on patient characteristics, treatment patterns and clinical outcomes. The objective is to describe how patients with myeloid diseases are treated; and to build a knowledge base regarding the effectiveness and safety of first line and subsequent treatment regimens in both community and academic settings. Enrolled patients will receive treatment and evaluations for their disease according to the standard of care and routine clinical practice at each study site. All treatments that patients receive for their disease will be recorded, including initial treatment and any subsequent therapy. Data on treatment outcomes, including response rates as measured by the treating physician, evidence of progression, survival, and patient-reported outcomes will be collected quarterly on the electronic CRF.

RA-PRO PRAGMATIC TRIAL

Treatment of RA with a non-TNFi biologic (rituximab, abatacept, tocilizumab, or sarilumab) was associated with improved function, quality of life, and productivity. TsDMARDs (tofacitinib, baricitinib, upadacitinib) were similarly effective. No meaningful differences were noted in non-TNFi-biologic vs. tsDMARD, but head-to-head studies of biologics are lacking. HAQ is a sensitive outcome for RA trials. A PCORI systematic review for early RA treatment concluded that "Evidence was insufficient to evaluate any differences between biologics for their impact on either functional capacity or HRQOL", a key knowledge gap our study will fill. The 2021 ACR RA treatment guideline, based on widely acknowledged low to moderate quality evidence, recommends switching to a non-TNFi biologic or a tsDMARD in patients with active RA despite the use of a TNFi-biologic. In practice, most patients receive another TNFi-biologic first, i.e., a second TNFi. This is not based on solid evidence, but on arbitrary algorithms often proposed by health insurance plans, and physician experience (first TNFi launched 22 yrs ago vs. the first tsDMARD 8 yrs ago vs. first non-TNF-biologic launched 17 years ago). This study will fill a critical knowledge gap by generating CER data for important PROs between these treatment options. This will facilitate informed decision-making, since PROs may be more sensitive to different mechanisms of action, and are highly relevant to patients. The proposed study will also provide needed evidence for real-world treatment decisions made by public and private payers. This head-to-head pragmatic trial will be the first to provide CER data for improvement in key PROs with recommended strategies in active RA despite the use of a TNFi-biologic and addresses PCORI and IOM priority areas by comparing the two most commonly used RA treatment strategies for people with active RA despite the use of a TNFi-biologic. This research is patient-centered, as study outcomes were identified by patients and payers. Currently, treatment choices are based on physician experience and insurance payer limitations. Investigators will generate evidence to help patients make decisions for themselves based on outcomes they care most about based on the relative efficacy of outcomes. Investigators will: (1) compare improvements in PROs with RA treatment strategies to each other using a state-of-the-art real-world pragmatic effectiveness study design, which will for the first time include most RA patients with comorbidities;(2) compare their toxicity in a real-world population for TNFi-biologic vs. tsDMARD. To our knowledge, no previous RCT comparing these drugs has examined a PRO as a primary outcome in RA, which our study will pioneer by using HAQ. HAQ is sensitive to change with effective treatments.

Randomized Study in Children and Adolescents With Migraine: Acute Treatment