Evaluation of Early Noradrenaline Hydrochloride Versus Standard Fluid Therapy in Non-Bleeding Hypotensive Patients: A Multi-Center Randomized Controlled Trial

The primary objective of this study is to evaluate the efficacy of **early initiated vasopressor therapy**, specifically using **noradrenaline**, compared to standard fluid therapy alone in non-bleeding hypotensive patients presenting in the emergency department (ED). The study aims to determine if this approach can improve the time to achieve shock control and subsequently reduce the necessity for intensive care unit (ICU) admission. This is clinically relevant as it may offer a more effective treatment strategy for managing hypotension and shock in emergency settings, potentially improving patient outcomes and resource utilization.

The clinical trial involves a study population comprising both **male** and **female** participants, aged 18 years and older, who present with signs or suspicion of **hypotension** or **shock**. The trial does not specify the total number of participants, as the sponsor has not provided this information. Participants were selected based on specific inclusion criteria, including having a systolic blood pressure (SBP) of less than 100 mmHg or a mean arterial pressure (MAP) of less than 65 mmHg, combined with a lactate level greater than 2.0 mmol/L. Additionally, participants must have received at least 500 ml of intravenous fluid prior to study inclusion. The study population includes individuals who are considered vulnerable, and the Clinical Frailty Score (CFS) is utilized to assess eligibility, with a score of 4 or less being a general requirement. However, if the CFS is 5 or higher, the treating physician's assessment of suitability for intensive care unit (ICU) admittance is considered, with consultation from an ICU consultant if necessary. The trial aims to evaluate the efficacy of early initiated vasopressor therapy compared to fluid therapy alone in improving time to shock control and reducing the need for ICU admittance in non-bleeding hypotensive patients.

The clinical trial is designed as a **randomized controlled trial** to evaluate the efficacy of early initiated vasopressor therapy using **noradrenaline hydrochloride** compared to standard fluid therapy in patients with **hypotension** or **shock** in the emergency department. The trial is multi-center and pragmatic, aiming to improve time to shock control and reduce the need for intensive care unit (ICU) admittance. The study will enroll adult participants, aged 18 years or older, who exhibit signs or suspicion of hypotension or shock, defined by specific blood pressure and lactate criteria. Participants must have received at least 500 ml of intravenous fluid prior to inclusion. The trial will exclude individuals based on criteria not specified in the source data.

The trial will commence with a screening visit to confirm eligibility based on the inclusion criteria. Following randomization, participants will receive either the investigational treatment or standard care. The primary endpoint is the proportion of patients achieving a target blood pressure within 90 minutes post-inclusion. Secondary endpoints include the number of ICU-free days alive within 30 days, time without shock within 24 hours, and both 30-day and in-hospital all-cause mortality rates.

Participants will be involved in the study for a maximum treatment period of one day, with follow-up visits scheduled to assess the primary and secondary outcomes. The trial is expected to conclude by August 31, 2026. Conditions that may lead to early termination from the study include withdrawal of consent or any adverse events that compromise participant safety. The trial is categorized as low-intervention due to the use of an authorized medication with a well-established safety profile. The study is conducted in accordance with ethical guidelines and regulatory requirements to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **noradrenaline hydrochloride**, also known as **norepinephrine hydrochloride**, as the experimental medication. This compound is a chemically synthesized vasoactive agent, classified under the ATC code C01CA03. The pharmaceutical form of the medication is designated as PHF00231MIG. The administration route is via **IV infusion**, with a maximum daily dose of 216 µg/Kg microgram(s)/kilogram. The total maximum dose is also 216 µg/Kg microgram(s)/kilogram, and the treatment period is limited to one day. The medication is not a pediatric formulation and is not classified as an orphan drug. The primary role of this medication in the trial is to serve as the test product in evaluating the efficacy of early initiated vasopressor therapy in hypotensive patients.

In addition to the experimental treatment, the study includes a comparator treatment, which is the standard-of-care therapy involving primarily fluid therapy. This non-experimental treatment serves as the control arm in the trial, allowing for a comparison of outcomes between early vasopressor therapy and conventional fluid therapy in non-bleeding hypotensive patients. The trial aims to assess whether the early use of noradrenaline can improve the time to shock control and reduce the need for intensive care unit admission compared to fluid therapy alone.

Efficacy in this clinical trial will be assessed by evaluating both primary and secondary endpoints. The primary endpoint is the proportion of patients achieving either a systolic blood pressure (SBP) greater than 100 mmHg or a mean arterial pressure (MAP) greater than 65 mmHg, or a target blood pressure set by the treating physician, measured at 90 (±15) minutes after inclusion. This will determine the immediate effectiveness of early initiated vasopressor therapy using **noradrenaline hydrochloride** compared to standard fluid therapy in non-bleeding hypotensive patients.

Secondary endpoints include the number of intensive care unit (ICU) free days alive within 30 days, time without shock within 24 hours, 30-day all-cause mortality, and in-hospital all-cause mortality. These endpoints will provide additional insights into the longer-term benefits and potential survival advantages of the treatment. The efficacy parameters will be collected and analyzed at specified time points to ensure comprehensive assessment of the treatment's impact on patient outcomes.