Capillary Refill Time-Targeted Resuscitation in Early Septic Shock Using Sodium Chloride and Lactated Ringer's Solution: A Hemodynamic Phenotype-Based Study

The primary objective of the study titled "Hemodynamic Phenotype-Based, Capillary Refill Time-Targeted Resuscitation In Early **Septic Shock**: ANDROMEDA-SHOCK-2" is to evaluate whether a capillary refill time (CRT)-targeted resuscitation strategy, based on clinical hemodynamic phenotyping, can improve a hierarchical clinical outcome in patients with septic shock. This outcome includes mortality, time to cessation of vital support, and length of hospital stay, all assessed within a 28-day period, compared to usual care. The clinical relevance of this objective lies in its potential to enhance patient outcomes by optimizing resuscitation strategies in septic shock, a condition associated with high mortality and morbidity.

The clinical trial focuses on adult patients aged 18 years and older diagnosed with **septic shock** as per the Sepsis-3 consensus conference criteria. The study population includes both male and female participants, with no specific vulnerable populations being targeted. The sponsor has not provided information regarding the total number of participants. Participants were selected based on the presence of septic shock, characterized by suspected or confirmed infection, hyperlactatemia, and norepinephrine requirements due to persistent hypotension following a fluid load of at least 1000 mL within one hour. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The selection criteria ensure that the study population is representative of the general adult population affected by septic shock, without additional restrictions based on lifestyle or health status beyond the primary condition. The trial aims to evaluate the effectiveness of CRT-targeted resuscitation in improving clinical outcomes compared to usual care within a 28-day period.

The clinical trial is designed to evaluate the efficacy of a **capillary refill time**-targeted resuscitation strategy in patients with **septic shock**. This study employs a randomized, double-blind, controlled trial design to ensure the reliability and validity of the results. The trial is expected to commence on December 19, 2024, and conclude by December 19, 2025, with a total duration of approximately one year. Participants will be involved in the study for a maximum treatment period of one day, with the primary endpoint being a hierarchical composite of all-cause mortality, time to cessation of vital support, and length of hospital stay, all assessed within 28 days.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is determined based on the Sepsis-3 consensus criteria for septic shock. This includes suspected or confirmed infection, hyperlactatemia, and norepinephrine requirements due to persistent hypotension after a fluid load of at least 1000 mL in one hour. Follow-up visits will be conducted to monitor the participants' response to the intervention and to collect data on the primary and secondary endpoints. The end-of-study visit will occur at the conclusion of the 28-day follow-up period, where final assessments will be made.

Participant involvement is expected to last for the duration of the treatment period and the subsequent 28-day follow-up. Conditions that may lead to early termination from the study include withdrawal of consent, adverse events that contraindicate continued participation, or any other medical condition that, in the opinion of the investigator, warrants discontinuation. The trial will utilize two solutions for infusion: Suero Fisiológico Vitulia 0.9% and Lactato Ringer Braun, both administered via intravenous infusion, with a maximum daily dose of 3000 mL. The study aims to provide insights into the potential benefits of a hemodynamic phenotype-based resuscitation strategy compared to standard care in improving outcomes for patients with septic shock.

The clinical trial involves the administration of **Suero Fisiológico Vitulia 0.9%**, a **sodium chloride** solution for infusion. This experimental medication is provided in the form of a solution specifically designed for intravenous infusion. The maximum daily dose is set at 3000 ml, with the same amount being the maximum total dose allowed during the treatment period. The administration is conducted via intravenous infusion, ensuring the solution is delivered directly into the bloodstream. The treatment period is limited to a maximum of one day. The solution is manufactured by Laboratorios ERN, S.A., and is classified under the ATC code B05BB, which pertains to solutions affecting the electrolyte balance.

Another experimental treatment used in the trial is **Lactato Ringer Braun**, a solution for infusion containing a combination of **potassium chloride, sodium chloride, calcium chloride dihydrate, and sodium lactate**. This solution is also administered intravenously, with a maximum daily and total dose of 3000 ml, similar to the sodium chloride solution. The treatment period is restricted to one day. The solution is produced by B. Braun Medical Lda. and falls under the ATC code B05BB01, which is categorized as electrolytes. Both solutions are not formulated for pediatric use and are not classified as orphan drugs.

Efficacy in the clinical trial titled "Hemodynamic Phenotype-Based, Capillary Refill Time-Targeted Resuscitation In Early Septic Shock: ANDROMEDA-SHOCK-2" will be assessed using a hierarchical composite primary endpoint. This endpoint includes all-cause mortality within 28 days, time to cessation of vital support (truncated at 28 days), and length of hospital stay (truncated at 28 days). The primary objective is to determine if a capillary refill time (CRT)-targeted resuscitation strategy, based on clinical hemodynamic phenotyping, can improve these outcomes in patients with **septic shock** compared to usual care.

The secondary endpoint focuses on all-cause mortality within 28 days. The trial will involve consecutive adult patients (≥ 18 years) diagnosed with septic shock according to the Sepsis-3 consensus, characterized by suspected or confirmed infection, hyperlactatemia, and norepinephrine requirements due to persistent hypotension after a fluid load of at least 1000 mL in 1 hour. The efficacy parameters will be measured and collected at specified time points, with the primary and secondary endpoints evaluated at the 28-day mark. The trial is designed to assess whether the CRT-targeted resuscitation approach can lead to better clinical outcomes compared to standard care practices.