Karlshamn, Sweden

Study to Evaluate the Effect of Balcinrenone/Dapagliflozin in Patients With Heart Failure and Impaired Kidney Function

The purpose of this study is to investigate the effect of balcinrenone/dapagliflozin compared with dapagliflozin, on the risk of CV death, HF event with and without hospitalisation, in patients with chronic HF, impaired kidney function, and who have had a recent HF event. Eligible patients will randomly be assigned with a 1:1:1 ratio to receive once daily administration of one capsule and one tablet of one of the following treatments: 1. Balcinrenone/dapagliflozin 15 mg/10 mg capsule and matching placebo for dapagliflozin 10 mg tablet 2. Balcinrenone/dapagliflozin 40 mg/10 mg capsule and matching placebo for dapagliflozin 10 mg tablet 3. Dapagliflozin 10 mg tablet and matching placebo for balcinrenone/dapagliflozin capsule The study is event driven, and the average study duration for a participant is estimated to be 22 months including screening period, 20 months blinded treatment period and a one-month follow-up period on open-label dapagliflozin. The study will be conducted at approximately 700 sites in approximately 40 countries globally.

A Study to Test the Long-term Safety and Tolerability of Brivaracetam in Study Participants With Childhood Absence Epilepsy or Juvenile Absence Epilepsy

Study of Zanzalintinib (XL092) + Pembrolizumab vs Pembrolizumab in Subjects With PD-L1 Positive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Antimicrobial Resistance in Acute Cholangitis

Given the extensive utilization of antibiotics and the worldwide rise of multidrug-resistant organisms, there are ongoing initiatives to ascertain microbiological traits and discern patterns of drug resistance associated with intra-abdominal infections. Microbial cultures from bile and blood samples will be established and characterized using appropriate methodologies. For patients with moderate and severe acute cholangitis (AC), blood cultures will be initiated upon admission, adhering to the Tokyo Guidelines for AC 2018 recommendations. Bile specimens will be obtained after cannulation through the sphincterotome before the therapeutic intervention. Initially, a minimum of 5 mL of the procured bile will be discarded, followed by the collection of an additional 5 mL in a sterile vessel containing a medium conducive to both anaerobic and aerobic bacterial cultures. The samples will undergo a minimum incubation period of seven days at 37 °C until microbial proliferation becomes evident. Antibiotic susceptibility assessments, specifically minimum inhibitory concentration (MIC), will be performed and interpreted according to established guidelines.The analysis of samples will occur within the laboratory of each respective center, with antibiograms conducted in accordance with established protocols.

A Study of Sigvotatug Vedotin Versus Docetaxel in Previously Treated Non-small Cell Lung Cancer

A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults With Severe Eosinophilic Asthma.

This is a multicenter, randomized, double-blind, placebo controlled, parallel group study designed to evaluate the efficacy and safety of dexpramipexole in adults and adolescents with severe, inadequately controlled asthma with eosinophilic phenotype on medium to high-dose inhaled corticosteroids (ICS )and at least one additional asthma controller medication with or without oral corticosteroids (OCS). Approximately 1400 participants will be randomized globally. Participants will receive dexpramipexole, or placebo, administered orally, over a 52-week treatment period. The study also includes a post-treatment follow-up period of 4 weeks.

Study of Bulevirtide in Participants With Chronic Hepatitis D Infection

The study design time perspective is retrospective and prospective for participants who previously participated in MYR-Reg-02 and are currently receiving BLV and prospective for participants who are scheduled to receive BLV.

Rhu-pGSN for Acute Respiratory Distress Syndrome (ARDS)

Potential subjects hospitalized with pneumonia or other infections are to be screened within 24 hours of diagnosis of ARDS. The Sponsor aims to identify as early as possible patients in the hospital who have developed acute hypoxemic respiratory failure within 7 days of the precipitating infection (often fever, rigors, chills, increased heart rate, increased respiratory rate, pain, cough, etc.) leading to ARDS resulting in mechanical or noninvasive ventilation or high-flow nasal oxygen (HFNO) supplementation with ≥50% O2 at a flow rate of ≥30 L/min. Patients who do not qualify for the study at the initial screening visit because of mild ARDS may subsequently progress to moderate-to-severe ARDS and should be reassessed at least daily for the 7 days following the precipitating infection. Once informed consent is obtained, the following assessments/procedures will be performed: 1. Confirm the potential participant has acute hypoxemic respiratory failure qualifying as moderate-to-severe ARDS for ≤48 hours following a suspected or confirmed infection within the preceding week. Moderate-to-severe ARDS is defined by the calculated or estimated ratio of arterial pressure of O2 to the fraction of inspired O2 [P/F ratio] ≤150. The P/F ratio will be computed from the most recent arterial blood gas obtained no more than 12 hours earlier than randomization. For potential subjects on high-flow nasal oxygen with ≥50% O2 at a flow rate of ≥30 L/min, the P/F ratio will be estimated assuming 50% delivered O2. If eligible and entered in the trial, the following steps should be taken. 2. Record medical history, including concomitant medications and current clinical status. Specify the site and etiology (if known) of infection, indicating if the lung ("direct ARDS") or another organ ("indirect ARDS") is the primary site of infection. 3. Perform pregnancy test (urine or blood) for women of childbearing potential if not already performed during the current hospitalization. 4. Collect pretreatment blood samples for measurement of baseline pGSN and analysis of antibodies against pGSN. 5. Perform physical examination and document results of the chest x-ray (CXR) and/or computed tomography (CT) scan, if CXR is inadequate if not already available as per SOC. 6. Obtain blood and sputum cultures and electrocardiogram (EKG) per SOC (if not already performed). Document the site of infection by collecting specimens as indicated: sputum (bacterial, viral, and mycobacterial, as indicated) and blood cultures, sputum Gram-stains, antigen detection on respiratory and urine specimens, and syndromic nucleic acid amplification tests (NAATs) on respiratory specimens (including a viral and other respiratory pathogen polymerase chain reaction [PCR] panel), where possible. Other specimens from possible sites of infection (e.g., urine, intra-abdominal drainage, skin or soft-tissue abscesses) should be cultured when available. 7. Measure routine lab tests at local (hospital) laboratory per local custom/SOC collect aliquots f- blood for subsequent biomarker assays (including, but not limited to C-reactive protein [CRP], procalcitonin, interleukin [IL]1β, IL6, IL10, and tumor necrosis factor [TNF]) for analysis at the central laboratory. 8. If eligibility criteria are satisfied, the subject will be randomized 1:1 (rhu-pGSN:placebo) by site to a treatment group and treated within 12 hours of randomization and no later than 48 hours after the diagnosis of moderate-to-severe ARDS. Randomized subjects will receive the assigned dose of rhu-pGSN or an equal volume of visibly indistinguishable sterile saline placebo as soon as possible but beginning no later than 48 hours after the diagnosis of moderate-to-severe ARDS. After reconstitution, rhu-pGSN is not to be kept at room temperature for >2 hours prior to beginning study drug administration. A single loading dose of rhu-pGSN at 24 mg/kg followed by 5 daily doses of rhu-pGSN at 12 mg/kg of measured or estimated actual body weight starting 24 hours after the loading dose or an equal volume of indistinguishable saline placebo will be administered. A window of ±2 hours will be allowed around dosing times. Study drug is administered by an IV push through a 0.2 μm filter. The syringe, filter, and extension tubing for administration of study drug are to be connected as close to the subjects as possible. The primary efficacy endpoint of all-cause mortality will be assessed at Day 28. All-cause mortality will also be assessed on Days 7 and 14. Discharged subjects will undergo follow-up evaluation on Days 14 and 28, preferably but not necessarily in person. Survival at Day 60 will be confirmed by telephonic contact or after 3 failed attempts, review of hospital and public records that document survival or death. Screening laboratory and other tests may be used as baseline values and do not need to be repeated if performed within 24 hours prior to randomization unless otherwise dictated by SOC. However, the blood sample for analysis of pGSN levels is to be repeated if not collected within 15 minutes before initiating the first dose of study drug. Repeat CXRs and/or CT scans and labs/cultures are to be obtained during the hospitalization if/when indicated by SOC. On Days 1 (predose) and 28, blood samples for analysis of antibodies against pGSN are to be collected, if possible. Repeat blood and other cultures should be obtained per SOC. An independent Data and Safety Monitoring Board (DSMB) consisting of at least 2 physicians and 1 statistician with appropriate scientific and medical expertise will be formed, and its roles and responsibilities will be described in the DSMB charter. The DSMB will perform 5 periodic reviews of safety data emphasizing deaths and SAEs and will monitor stopping rules to pause enrollment. There will be no pause on enrollment during the planned unblinded periodic reviews. These reviews will be performed after the first 50, 100, 200, 300, and 400 subjects in the Safety Analysis Set have either completed 28 days of follow-up, have died, or have discontinued from the study prior to completing 28 days of follow-up. DSMB members will be provided with unblinded data. Based on the results of each of the planned periodic reviews, the study will be paused only if there is a relative increase of 25 percentage points in the incidence of death or SAEs in the rhu-pGSN treatment group compared to the placebo group. A futility analysis will be performed at the 300-subject review. The Sponsor will take appropriate action based on the recommendation of the DSMB. The DSMB will also review expedited reports of any SAEs throughout the study and may request additional looks at safety data at their discretion. Enrollment will continue during all safety analyses unless otherwise recommended by the DSMB chair.

CovidDB: The Covid-19 Inpatient Database

The exponentially increasing number of SARS-CoV-2 infected people, despite the influence of the currently existing non-medical measures, is generating a rapidly increasing number of inpatients, some of whom need artificial ventilation. The average focus is on the extent to which the hospitals' capacities will be sufficient to adequately treat all patients. Regardless of this, it can be expected that even if the non-medical measures are successful, the number of inpatients treated will remain high in the course of the pandemic. With regard to the distribution of infection, it can be expected that clinics with a wide range of expertise will have to treat a large number of Covid-19 patients. So far, however, there is little to no experience in treating patients. In addition to epidemiological data, only case descriptions and some Chinese studies mostly from Wuhan based on fewer patients are available. In view of the rapidly spreading pandemic, preprints are increasingly being used. What has been missing so far is a uniform, structured recording of the courses of Covid-19 inpatients handled by many clinics, which goes beyond the epidemiological events in terms of depth of detail. With this documentation of real processes, the basis for a large number of studies and the associated better understanding of the disease process could be created. The current dynamics make it imperative that the clinics, even those who have not received the most up-to-date scientific knowledge, cannot wait for the results of studies, but rather need concrete help in the treatment of patients. Efficient assistance within the framework of a close exchange between the treatment units is only possible with a multicentre, uniform documentation environment. The aim of the project is to better understand the Covid-19 inpatient course of the disease and to quickly identify the positive experiences in the treatment in order to update guidelines for the treatment and use of medication.

Apremilast Pediatric Study in Children With Active Juvenile Psoriatic Arthritis