Evaluation of Reduced Noradrenaline Tartrate Use in Cardiogenic Shock Post-Acute Myocardial Infarction: Impact on Mortality and Renal Failure

The primary objective of this study is to evaluate whether a treatment strategy involving reduced use of **noradrenaline** in patients with cardiogenic shock, secondary to acute myocardial infarction, is superior to standard care in terms of combined all-cause mortality and renal failure at 30 days. This is clinically relevant as it aims to improve survival rates and renal outcomes in a critical patient population.

Secondary objectives include assessing whether the reduced use of noradrenaline leads to: - Lower all-cause mortality at 30 days. - Reduced cardiovascular death at 30 days. - An increase in the number of days patients are alive and out of the hospital at 30 days.

The clinical trial involves a total of **40 participants** diagnosed with **acute myocardial infarction** complicated by cardiogenic shock. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on specific inclusion criteria, such as having experienced an acute myocardial infarction, either STEMI or NSTEMI, and having undergone early revascularization by PCI. The trial also targets individuals exhibiting cardiogenic shock, characterized by low systolic blood pressure, impaired organ perfusion, and clinical signs of pulmonary congestion. The trial population includes a vulnerable group, indicating that special considerations are in place to ensure their safety and ethical treatment. Lifestyle factors such as diet, physical activity, and habits are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of a treatment strategy involving reduced use of **noradrenaline** in patients experiencing cardiogenic shock due to acute myocardial infarction. This study is a **randomized**, controlled trial with an estimated duration from January 2024 to October 2025. The primary objective is to determine if this strategy is superior to standard care in reducing all-cause mortality and severe renal failure within 30 days post-randomization. Participants will be randomly assigned to either the intervention group receiving reduced noradrenaline or the control group receiving standard care. The trial is categorized as a low-intervention study, as it involves minimal additional risk and uses an already authorized medicinal product in accordance with its marketing authorization.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as having an acute myocardial infarction, undergoing early revascularization by PCI, and exhibiting clinical signs of cardiogenic shock. Follow-up visits will be scheduled to monitor the participants' health status and treatment outcomes, with the primary endpoint being assessed at 30 days. The end-of-study visit will occur at the conclusion of the trial period, where final assessments will be conducted. The expected length of participant involvement is approximately 30 days, with conditions for early termination including withdrawal of consent or adverse events that compromise participant safety.

The primary endpoint is a composite of all-cause mortality and severe renal failure requiring renal replacement therapy within 30 days. Secondary endpoints include all-cause mortality at 30 days and the number of days participants are alive and out of the hospital within the same period. The trial's low-intervention nature means that no additional labeling of the product is required, and the study does not involve blinding. This approach ensures that the trial remains aligned with the definitions set forth in the EU Clinical Trial Regulation 536/2014, maintaining a focus on standard treatment while minimizing risk to participants.

The clinical trial involves the use of **noradrenaline tartrate** as the experimental medication. Noradrenaline tartrate, also known by synonyms such as norepinephrine bitartrate and levarterenol acid tartrate, is a chemical substance classified under the ATC code C01CA03. The pharmaceutical form of noradrenaline tartrate is designated as PHF00230MIG. The medication is administered via **intravenous infusion**. The dosing regimen allows for a maximum daily dose of 18 mg, with a total maximum dose of 200 mg over the course of the treatment. The maximum treatment period is set at 10 days. The primary objective of the trial is to evaluate the efficacy of a reduced use of noradrenaline in patients with cardiogenic shock resulting from acute myocardial infarction, comparing it to standard care in terms of combined all-cause mortality and renal failure at 30 days.

In addition to the experimental treatment, the study may involve the use of standard-of-care therapy as a comparator. The standard-of-care therapy is not explicitly detailed in the provided data, but it typically includes treatments that are widely accepted and used in clinical practice for managing cardiogenic shock. The trial does not involve the use of a placebo. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment protocol. The trial does not include a pediatric formulation, and noradrenaline tartrate is not classified as an orphan drug for this study.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the composite of all-cause mortality and severe renal failure requiring renal replacement therapy within 30 days after randomization. Secondary endpoints include all-cause mortality at 30 days and the number of days alive and out of the hospital within the same period. These endpoints will provide a comprehensive measure of the treatment's impact on patients with **cardiogenic shock** resulting from acute myocardial infarction.

The trial will employ a treatment strategy involving reduced use of noradrenaline, comparing its efficacy against standard care. The primary objective is to determine if this strategy is superior in terms of the combined outcomes of mortality and renal failure. The study is designed as a low-intervention clinical trial, in accordance with EU Clinical Trial Regulation 536/2014, and will not involve blinding or additional product labeling, as noradrenaline is used within its authorized indications.