Haag In Oberbayern, Germany

Recombinant Factor VIIa (rFVIIa) for Hemorrhagic Stroke Trial

The investigators will perform a global, Phase III, randomized, double-blind controlled trial of rFVIIa plus best standard therapy vs. placebo and best standard therapy alone. The investigators will include participants with a volume of ICH ≥ 2 and < 60 cc, no more than a small volume of intraventricular hemorrhage (IVH) (IVH score ≤ 7), age ≥ 18 and ≤ 80, Glasgow Coma Scale of ≥ 8, and treated within 120 minutes from stroke onset. To minimize time-to-treatment, the study will use emergency research informed consent procedures (including exception from informed consent (EFIC) in the United States) and mobile stroke units (MSUs), with a goal of ½ of participants treated within 90 minutes, as accomplished in the NINDS t-PA trials. The FASTEST Trial will include approximately 100 hospital sites and at least 15 MSUs in the NINDS-funded StrokeNet and key global institutions with large volumes of ICH patients and the ability to treat them within 120 minutes of stroke onset. Recruitment of 860 participants over 3½ years is planned. Countries participating in the trial include the United States, Canada, Japan, Germany, Spain, and the United Kingdom. Involving other countries may be possible in the future depending upon recruitment needs. Participants will be randomized in a double-blinded fashion to rFVIIa 80 µg/kg dose (maximum 10 mg dose) or placebo. Participants in both arms will receive best standard therapy as per published AHA Guidelines for ICH, including a target systolic blood pressure of 140 mm Hg. The primary outcome (ordinal mRS with the following categories: 0-2, 3, and 4-6) will be determined at 180 days, but participants will be followed by remote assessment at 30 days and 90 days. To measure growth of ICH, all participants will have a standard of care baseline non-contrast CT of the head and a repeat scan at 24 hours. Centralized volumetric measurements of ICH, IVH, and edema will be performed for both time points. Novo Nordisk A/S will manufacture and supply rFVIIa as a research medication for use in the FASTEST Trial. Novo Nordisk A/S will also manufacture and supply matching placebo that is identical to rFVIIa in appearance and administration.

A Study of Baricitinib in Participants From 1 Year to Less Than 18 Years Old With Juvenile Idiopathic Arthritis

A Study Evaluating the Efficacy and Safety of Adjuvant Giredestrant Compared With Physician's Choice of Adjuvant Endocrine Monotherapy in Participants With Estrogen Receptor-Positive, HER2-Negative Early Breast Cancer (lidERA Breast Cancer)

A Study Evaluating the Efficacy and Safety of Multiple Therapies in Cohorts of Participants With Locally Advanced, Unresectable, Stage III Non-Small Cell Lung Cancer (NSCLC)

Interfant-21 Treatment Protocol for Infants Under 1 Year with KMT2A-rearranged ALL or Mixed Phenotype Acute Leukemia

All infants that are eligible for this study and for whom the parents/legal representatives give informed consent will be enrolled in this study. All patients will receive one cycle of blinatumomab on top of the standard treatment backbone after induction therapy. Medium risk patients, that respond well to the 1st cycle will be treated with a 2nd cycle of blinatumomab replacing one chemo course after consolidation therapy. If they do not respond well enough they will be treated according to the current treatment standard. Minimal residual disease will be used to determine the response to blinatumomab. High risk patients will be eligible for allogeneic stem cell transplantation after the first blinatumomab cycle if they are Minimal Residual Disease (MRD) negative (defined as < 0.01%). Also medium risk patients with insufficient MRD response after induction or after the 1st cycle of blinatumomab will be allocated to high risk treatment and will be eligible for allogeneic stem cell transplantation.

Pivotal 2 Study of RGX-314 Gene Therapy in Participants With nAMD

This randomized, partially masked, controlled, Phase 3 clinical study will evaluate the efficacy and safety of ABBV-RGX-314 gene therapy in participants with nAMD. The study will evaluate 2 dose levels of RGX-314 gene therapy relative to an active comparator. The primary endpoint of this study is mean change in best-corrected visual acuity (BCVA) of ABBV-RGX-314 relative to aflibercept. Approximately 660 participants who meet the inclusion/exclusion criteria, will be enrolled into one of 3 arms.

A Study of Guselkumab in Participants With Fistulizing, Perianal Crohn's Disease

Immediate Necrosectomy vs. Step-up Approach for Walled-off Necrosis

Pancreatic fluid collection is a late complication of severe acute pancreatitis. According to the revised Atlanta classification, walled-off necrosis (WON) is defined as an encapsulated collection of necrotic tissue that is observed after four weeks of the onset of acute pancreatitis. Infected WON is associated with high morbidity and mortality; therefore, an appropriate treatment, including antibiotics and drainage, is mandatory. With the development of endoscopic equipment, endoscopic ultrasonography (EUS)-guided drainage has become a first-line treatment modality for infected WON. For patients who are refractory to EUS-guided drainage, endoscopic necrosectomy (EN) is a treatment option to facilitate direct removal of infected necrotic tissue within the WON. However, due to potentially lethal adverse events of EN, such as bleeding, perforation, and peritonitis, EN is usually withheld for several days after EUS-guided drainage. This strategy is known as "the step-up approach." Recently, with the accumulated evidence supporting the safety of EN, especially with the use of a dedicated lumen-apposing metal stent, it has been reported that EN immediately after EUS-guided drainage can shorten the treatment duration without increasing adverse events. Given these lines of evidence, the investigators hypothesized that immediate EN following EUS-guided drainage of WON might shorten time to clinical success compared to the step-up approach. To examine this hypothesis, the investigators planned to conduct a multicenter randomized controlled trial comparing treatment duration between EN immediately after EUS-guided drainage versus the step-up approach in patients with symptomatic WON.

ASIA Down Syndrome Acute Lymphoblastic Leukemia 2016

CFAE/Spatiotemporal Dispersion Guided Ablation Versus PVI Guided Ablation in Persistent AF

Design: A prospective, multicenter, randomized unblinded clinical study. Objective: The purpose of this study is to compare the efficacy and safety of ablation of AF drivers marked by spatiotemporal dispersions and CFAEs guided ablation to PVI guided ablation in patients with persistent AF. Hypothesis: CFAE/spatiotemporal dispersion guided ablation will increase AF free survival compared to a PVI guided ablation. Enrollment: 180 patients will be enrolled in this study. Clinical Sites: International (including non EU-countries), multicenter study. Patient population: Patients with persistent AF (defined as atrial fibrillation which is sustained beyond 7 days but no more than one year, or lasting less than 7 days but necessitating pharmacologic or electrical cardioversion, but lasting longer than 48 hours) should be documented either on 12-lead ECG, transtelephonic monitoring (TTM), ambulatory holter monitoring (HM) or telemetry strip and a physician's note showing continuous AF. Furthermore patients who have failed at least one Anti Arrhythmic Drug (AAD) (Class I or III) as evidenced by recurrent symptomatic AF or intolerable side effects of the AAD. Eligible patients who sign the study informed consent form will be randomized based on a 2:1 ratio into one of two study arms: - CFAE/spatiotemporal guided ablation: CFAE/spatiotemporal dispersion mapping and ablation during AF aimed at restoring sinus rhythm during ablation. Pulmonal vein isolation will be checked before and after ablation using a mapping catheter - PVI guided ablation: wide antral pulmonary vein isolation during mapping catheter control of pulmonary vein signals Primary Endpoint: Freedom from recorded AF or atrial flutter or atrial tachycardia recurrences (>30 seconds) without the use of AADs through 18 months follow-up, post-blanking, on either a 12 lead ECG on visits or on 24 hour holter monitoring or on symptom driven event monitoring. CFAE/spatiotemporal dispersions procedural details: To increase the accuracy of CFAE mapping, the Pentaray mapping catheter will be used to define spatiotemporal dispersion areas of CFAEs as specific targets of ablation as described by Seitz (see also citation) as follows. Dispersion areas are defined as clusters of electrograms, either fractionated or non-fractionated, that display interelectrode time and space dispersion at a minimum of 3 adjacent bipoles such that activation spread over all the AFCL. At each bipole in a dispersion area, one or more of the following fractionated or nonfractionated electrogram morphologies can be found: 1. continuous, low-voltage fractionated electrograms ("continuously fractionated signal"); 2. bursts of fractionated electrograms ("trains of fractionation"); 3. fast nonfractionated electrograms (AFCL <120 ms; "rapid fires"); and 4. slow nonfractionated electrograms (AFCL >120 ms). Multipolar electrogram dispersion and non-dispersion regions, illustrate that fractionated electrograms are found in both dispersion and non-dispersion regions. CFAE software can be used, but CFAE ablation is not guided by the software, but based on visual judgement. Preferably a CFAE map will be made before ablation to judge the sites of most extensive CFAE sites. Baseline mapping in both atria will be performed during AF with the PentaRay multispline catheter sequentially positioned in various regions of the RA and LA. At each location, the catheter will be maintained in a stable position for a minimum of 2.5 s. The operator will look for dispersion areas (electrograms exhibiting both time and spatial dispersion). Where dispersion are found and/or the catheter is not stable for 2.5 s, acquisitions will be repeated. Additional risks: No additional risks are anticipated for patients enrolled in this study compared to patients undergoing ablation of symptomatic AF outside of the study, because the same catheter is used as in patients outside the study, and both methods (PVI and CFAE) are part of daily practice. Although none reported in the literature so far, CFAE ablation may cause more extensive lesions than other ablation for persistent atrial fibrillation, especially in the posterior wall. This in turn may cause pericardial effusion, myocardial rupture and atrio-esophageal fistula. All of these are potentially life threatening. However, energy settings are changed according to myocardial wall size and pressure recordings, in order to prevent these complications. Furthermore, also in the group of wide antral ablation, the posterior wall is targeted, possibly resulting in the same events. For prevention of posterior wall injury, temperature monitoring in the oesofagus may be used. Thrombus formation is a complication that can occur with any ablation technique. Thrombi may dislodge and embolize, causing a stroke, myocardial infarction or other ischemic event. Therefore, it is required that activated clotting time (ACT) is kept above 300 seconds. This should be monitored every 30 minutes, and heparin should be administered depending on the outcome. The operator is responsible for maintaining an adequate ACT. Radiation exposure during the fluoroscopic imaging of the catheters may result in an increase in the lifetime risk of developing a fatal malignancy (0.1%) or a genetic defect in offspring (0.002%). Potential Benefit: The direct benefit for patients undergoing ablation is the potential elimination of AF episodes. It is furthermore expected that quality of life will improve and less frequent hospitalization will be needed. Whether further morbidity as cerebral vascular events are prevented is subject to discussion. The information gained from the conduct of this study may benefit patients with AF by improving future treatment modalities.