Criciuma

Researchers are evaluating AZD0780, an oral PCSK9 inhibitor, in a phase 3, randomized, placebo-controlled study. This trial focuses on patients with established atherosclerotic cardiovascular disease ASCVD or those at high risk for a first ASCVD event. The study aims to assess how AZD0780 compares to placebo in reducing the risk of major adverse cardiovascular events, also known as MACE-PLUS, over the course of the trial. Participants are randomly assigned to receive either oral AZD0780 once daily or a matching placebo once daily. The study continues until a primary analysis censoring date, which may be up to approximately 54 months from randomization. After this, a study closure visit will be conducted as the final visit for each participant. During the study, participants will be regularly monitored for cardiovascular events including heart attacks, strokes, urgent coronary revascularizations, and other related outcomes. Researchers will track the time to first occurrence of these events as the primary outcome. Safety and other secondary outcomes like all-cause mortality will also be assessed. The total participation time can last up to about 54 months, with ongoing evaluations throughout this period.

Researchers are evaluating how well intranasal esketamine works alongside standard care to quickly reduce symptoms of major depressive disorder MDD in adolescents aged 12 to 17 who experience acute suicidal thoughts or behaviors. This Phase 3 study compares esketamine plus standard care with a psychoactive placebo plus standard care to assess symptom improvement in this vulnerable population. Participants receive either intranasal esketamine 84 mg twice weekly for 4 weeks with a possible dose reduction to 56 mg, or oral midazolam plus intranasal placebo with similar dosing schedules. The treatment period includes dosing on Days 1, 4, 8, 11, 15, 18, 22, and 25, with dose flexibility based on investigator judgment. This double-blind, randomized trial involves two groups receiving either the experimental or placebo regimen. During the study, participants are monitored through clinical assessments including the Childrens Depression Rating Scale - Revised CDRS-R at baseline and 24 hours after the first dose, among other measures of depressive symptoms and suicidality throughout the 25-day treatment. Safety is assessed via medical exams, vital signs, and ECG. The primary outcome focuses on depressive symptom changes within 24 hours, with secondary outcomes tracking symptom progression, remission, and suicidality severity during treatment.

Researchers are evaluating the effects of therapeutic-dose heparin compared to usual care pharmacological thromboprophylaxis in patients hospitalized with community-acquired pneumonia CAP. This international, open-label, randomized controlled trial aims to understand if higher doses of heparin can improve outcomes by addressing inflammatory and thrombotic processes that contribute to respiratory, cardiac, and organ complications in CAP. The study builds on findings from COVID-19 patients, where therapeutic-dose heparin showed benefits in non-critically ill patients. Participants are randomly assigned to one of two groups. One group receives a daily therapeutic dose of low molecular-weight heparin LMWH or unfractionated heparin UFH for up to 14 days or until hospital discharge. The other group receives usual care with thromboprophylactic dose anticoagulation following local protocols, with doses not exceeding half the therapeutic level. The investigational arm prefers LMWH but may use UFH, especially in cases of renal compromise, with dosing tailored to patient weight and local standards. During the study, participants will be monitored for survival over 30 days as the primary outcome. Secondary outcomes include bleeding events, heparin-induced thrombocytopenia HIT, thrombotic events, invasive mechanical ventilation, mortality at multiple time points, hospital-free days, and health-related quality of life. The study involves hospital assessments, close monitoring of safety and clinical status, and tracking of various health measures up to 180 days, ensuring comprehensive evaluation of the treatments under study.

Researchers are evaluating the effectiveness and safety of paltusotine compared to a placebo in adults with carcinoid syndrome caused by well-differentiated neuroendocrine tumors. This Phase 3 study aims to continue assessing the safety, efficacy, and how the body processes paltusotine. Carcinoid syndrome symptoms include flushing and frequent bowel movements, and the study focuses on these symptoms in affected adults. Participants are randomly assigned to receive either paltusotine at a dose of 80 mg daily or a placebo. The study includes several phases a screening period of up to 11 weeks to determine eligibility, a 16-week double-blinded treatment period where neither participants nor researchers know who receives the drug or placebo, followed by a 104-week open-label extension where all participants can receive paltusotine. After treatment, there is a 4-week follow-up period. During the study, participants will record daily flushing episodes and bowel movements using a diary to help measure the treatment effects. Researchers will monitor safety and treatment response throughout all phases. The total participation time can last over two years, including the screening, treatment, extension, and follow-up periods. This long-term approach helps assess both immediate and extended effects of paltusotine.

Researchers are evaluating the efficacy and safety of tozorakimab delivered under the skin in adults with uncontrolled asthma who are already using medium-to-high doses of inhaled corticosteroids. This phase IIb, double-blind, placebo-controlled study aims to find the optimal dosing range of tozorakimab in this population. The study is sponsored by AstraZeneca and uses a randomized, parallel design to compare different doses and placebo. Participants will receive subcutaneous injections of either tozorakimab at one of two dose levels or a placebo. The study arms include dosing with tozorakimab Dose 1, tozorakimab Dose 2, or placebo, administered under the skin. The treatment period lasts from 26 to 52 weeks, during which participants will be monitored for their asthma symptoms and lung function. Throughout the study, participants will undergo assessments including lung function tests such as forced expiratory volume in 1 second FEV1, asthma control questionnaires ACQ-6, quality of life questionnaires AQLQ12, and measurements of asthma exacerbations. Blood samples will be collected to measure drug levels and immune response. Safety and adherence will be closely monitored, and the primary outcome is the annualized rate of severe asthma exacerbations over the treatment period.

Septic shock is a serious condition marked by low blood pressure, reduced resistance in blood vessels, and poor response to drugs that tighten blood vessels. This condition involves nitric oxide affecting organ function, and researchers believe that changes in certain heart and blood vessel receptors, along with increased GRK2 enzyme activity, contribute to these problems. The study explores whether blocking GRK2 activity with paroxetine might improve heart and blood vessel function in patients with septic shock. Participants will be randomly assigned to receive either paroxetine or a placebo. Paroxetine is given as a 40 mg dose once daily by mouth or through an enteric tube for up to five days or until the shock resolves. The study is designed as a randomized, placebo-controlled trial with quadruple masking to evaluate the effects of paroxetine on cardiovascular function during septic shock. During the study, researchers will monitor how long it takes for patients to stop needing vasopressor drugs over 28 days. They will also track the total doses of vasopressors used in the first two and five days, changes in organ failure scores related to the heart and circulation, length of stay in the intensive care unit, and mortality during ICU stay. Patients will be closely assessed for these outcomes to understand paroxetines impact on septic shock recovery.

Researchers are evaluating the effect of seltorexant as an add-on treatment to antidepressants in adults and elderly people with major depressive disorder who also have insomnia symptoms and have not responded well to their current antidepressant therapy with SSRIs or SNRIs. This Phase 3 study aims to understand how well seltorexant works, its safety, and its ability to maintain improvement compared with a placebo. Participants in part 1 of the study will receive either seltorexant or a matching placebo once daily for 6 weeks, alongside their usual SSRI or SNRI antidepressant. Those who complete part 1 and meet criteria for part 2, plus new participants entering directly into part 2, will receive seltorexant during an open-label induction and stabilization phase. Participants who respond well will then enter a double-blind maintenance phase, receiving either seltorexant or placebo daily, continuing their baseline antidepressant throughout. During the study, participants will be monitored through rating scales measuring depression severity, sleep disturbance, and patient health questionnaires at baseline and specified days up to two years and ten months. Researchers will assess changes in depression symptoms and time to relapse, along with safety and tolerability. Participants will be followed through treatment phases and post-treatment periods to evaluate the maintenance of effects and overall safety.