Evaluation of Norepinephrine Versus Dobutamine Plus Norepinephrine in Cardiogenic Shock: A Randomized Controlled Trial

The primary objective of this study is to evaluate the difference in **lactate** variation associated with two therapeutic schemes in patients with **cardiogenic shock**: norepinephrine versus dobutamine plus norepinephrine. This is clinically relevant as lactate levels are a critical marker of tissue perfusion and metabolic status in patients experiencing cardiogenic shock, and optimizing treatment strategies can potentially improve patient outcomes.

Secondary objectives include evaluating the incidence of death, extracorporeal membrane oxygenation (ECMO) implantation, or left ventricular assist device (LVAD) implantation at 72 hours and at discharge. These outcomes are significant as they provide insight into the short-term and discharge-related impacts of the treatment strategies on patient survival and the need for advanced cardiac support interventions.

The clinical trial involves participants diagnosed with **cardiogenic shock**, a condition characterized by inadequate circulation of blood due to the heart's inability to pump effectively. The study population includes both male and female subjects, with an age range of 18 years and older. Participants are required to have a systolic systemic arterial pressure (SBP) of less than 90 mmHg or a mean arterial pressure (MAP) of less than 60 mmHg for at least 30 consecutive minutes, necessitating pharmacological support to maintain adequate blood pressure levels. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants were selected based on specific criteria, including the need for enrollment within 3 hours of the acute event and a Sequential Organ Failure Assessment (SOFA) score of less than 2. Written informed consent was also a prerequisite for inclusion in the study. Lifestyle factors such as diet, physical activity, and habits were not specified in the available data.

The clinical trial is designed to evaluate the difference in lactate variation associated with two therapeutic schemes in patients with **cardiogenic shock**. This is a randomized, double-blind, controlled trial comparing the effects of **noradrenaline tartrate** and **dobutamine** plus **noradrenaline**. The trial is categorized as a low-intervention clinical trial, as the investigational medicinal products are used in accordance with their marketing authorization, and the procedures pose minimal risks. The trial is expected to run from February 2022 to June 2026, with a maximum treatment period of 3 days for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age over 18 years, presence of cardiogenic shock, and a SOFA score of less than 2. Following randomization, participants will receive the assigned treatment via infusion. The primary endpoint is the change in blood lactate concentration from baseline to 72 hours post-randomization. Secondary endpoints include mortality or the need for ECMO/LVAD at 72 hours and discharge, changes in SOFA score, and lactate AUC over 72 hours.

Study visits will include follow-up assessments at 72 hours and at discharge, with the end-of-study visit marking the conclusion of the participant's involvement. The expected length of participant involvement is up to 7 days, depending on the clinical course. Conditions that may lead to early termination from the study include withdrawal of consent or adverse events that compromise participant safety. The trial aims to provide valuable insights into the management of cardiogenic shock, with a focus on optimizing therapeutic strategies.

The clinical trial involves the administration of **NORADRENALINE TARTRATE**, a **solution for infusion**. This experimental medication is classified under the pharmacotherapeutic group of adrenergic and dopaminergic agents, with an ATC code of C01CA03. The active substance, noradrenaline tartrate, is of chemical origin. The medication is administered via **infusion** at a maximum daily dose of 0.5 µg/Kg microgram(s)/kilogram, with a total maximum dose of 0.5 µg/Kg microgram(s)/kilogram. The treatment period is limited to a maximum of 3 days. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

Additionally, the trial includes the use of **DOBUTAMINE**, which is provided as a **concentrate for solution for infusion**. This medication belongs to the pharmacotherapeutic group of sympathomimetics, with an ATC code of C01CA04. The active substance, dobutamine, is also of chemical origin. Dobutamine is administered via **infusion** with a maximum daily dose of 10 µg/Kg microgram(s)/kilogram and a total maximum dose of 10 µg/Kg microgram(s)/kilogram. Similar to noradrenaline tartrate, the treatment period for dobutamine is capped at 3 days. Compliance with the dosing regimen is closely monitored to ensure the integrity of the trial data.

Both medications are utilized in the study to evaluate the difference in lactate variation associated with the therapeutic schemes of norepinephrine versus dobutamine plus norepinephrine in patients with cardiogenic shock. The trial does not involve any pediatric formulations, and neither medication is classified as an orphan drug. No non-experimental treatments, such as standard-of-care therapy or placebo, are specified in the trial protocol.

The efficacy of the clinical trial titled "Comparison between norepinephrine and dobutamine in patients with cardiogenic shock" will be assessed through both primary and secondary endpoints. The primary endpoint focuses on the **change in blood lactate concentration**. This will be measured as the difference between the maximum lactate value at baseline (0-1 hours after randomization) and 72 hours after randomization in the two treatment arms. In cases where a participant experiences death, the change will be calculated using the last available lactate value from randomization.

Secondary endpoints include several parameters: the occurrence of death or the need for ECMO/LVAD at 72 hours and at discharge, the change in SOFA score between baseline (0-1 hour from randomization) and 72 hours, as well as between baseline and 7 days from randomization. Additionally, the lactate area under the curve (AUC) from 0 to 72 hours and the need for additional extra-trial inotropes at 72 hours will be evaluated. These endpoints will be measured and collected at specified time points to ensure comprehensive analysis of the treatment efficacy.