Shock, Cardiogenic

The objective of this Phase 1b/2a trial is to evaluate the safety, tolerability, and exploratory efficacy of invobenitug (also known as procizumab), a monoclonal antibody under development for the treatment of cardiogenic shock (CS). CS is a life-threatening hypoperfusion of vital organs that frequently results in death. In addition to safety and tolerability, pharmacokinetics and pharmacodynamics of invobenitug are evaluated to define the optimum phase 2 dose (P2D) of invobenitug.

This clinical study was a multi-center, open-label, randomized controlled clinical trial. A total of 472 patients with early-stage cardiogenic shock were recruited and randomly divided into the experimental group and the control group, with 236 cases in each group. The HeartMed-HF digital out-of-hospital management was used to manage the patients in the experimental group, while the patients in the control group were managed according to the discharge guidance. The primary endpoints were 1-year all-cause mortality and unplanned readmission after randomization (excluding emergency department visits). Secondary endpoints (at 3 months, 6 months, and 12 months post-randomization) were: all-cause mortality, rehospitalization for HF, recurrent MI, ischemia-driven repeat revascularization, stroke, BARC 3-5 grade major bleeding, unplanned formal rehospitalization, types of GDMT medications or GDMT target dose achievement rate.

The investigators are interested in determining if there is a meaningful benefit from the use of medications purported to increase the pumping function of the heart (i.e. inotropes) among critically ill patients admitted to the Cardiac Intensive Care Unit (CICU). To do this, the investigators will conduct a multi-centre, double blind, randomized control trial with patients who are deemed to require these medications by their treating physician to one of the two most commonly used agents in Canada (Milrinone or Dobutamine) or placebo. Each patient will be closely monitored by their healthcare team. The dose of medication will be adjusted according to each patients' clinical status. After 12 hours, the participants will move to open label treatment and any continued use of inotropes will be at the discretion of their treating physician.

This study evaluates the safety and effectiveness of Ciprofol, a new sedative, in critically ill patients receiving Extracorporeal Membrane Oxygenation (ECMO), a life-support system for heart or lung failure. The investigation aims to: Assess how Ciprofol affects the oxygenator, a critical ECMO component responsible for adding oxygen to blood. Compare the safety of Ciprofol to midazolam, a commonly used sedative. Eligibility Criteria Adults aged 18 years or older. Patients receiving ECMO and mechanical ventilation for over 72 hours. Individuals requiring sedation for medical procedures. Study Protocol Participants will be randomly assigned to one of two groups: Ciprofol Group: Initial sedation dose of 0.1 mg/kg, adjusted as needed. Midazolam Group: Initial sedation dose of 0.05 mg/kg, adjusted as needed. Both groups will receive pain management with remifentanil. Sedation levels will be adjusted daily by the clinical team to ensure patient safety and comfort. Outcome Measures Primary: Oxygenator performance (oxygen and carbon dioxide levels) on Days 3 and 7. Secondary: Changes in blood triglyceride and clotting marker (D-dimer) levels, oxygenator lifespan before replacement, and safety outcomes such as low blood pressure, respiratory issues, or allergic reactions. Significance ECMO patients often require prolonged sedation, but current sedatives like midazolam may contribute to oxygenator damage. Ciprofol's potential for faster recovery and fewer side effects could improve sedation practices and device longevity in this high-risk population.

The present study is an International multicentric prospective observational cohort study. This will be an international research campaign to prospectively collect and analyze clinical data of all VA ECLS patients admitted to participating ICUs with a focus on LV venting modalities. The aims of the study are: * To investigate the meaning of LV overload during veno-arterial (VA) extracorporeal life support; * To extensively describe the left ventricular (LV) unloading strategy during VA extracorporeal life support in a large prospective international cohort. * To compare different strategies to unload the left ventricular in terms of efficacy and outcomes;