Evaluation of Phosphocreatine Sodium Versus Sodium Chloride in Patients Treated by Medical Emergency Teams: A Randomized Clinical Trial

The primary objective of this clinical trial is to evaluate the effect of **phosphocreatine** (PCr) compared to a placebo (saline solution) on the number of days patients are alive and out of the hospital at 30 days (DAOH30). This measure is clinically relevant as it assesses the potential of PCr to improve patient outcomes by reducing hospital stay duration and enhancing survival rates in patients treated by a medical emergency team (MET) in general wards. The secondary objective is to determine the superiority of PCr over placebo in improving cognitive function at 30 days in the same patient population. This is important for understanding the broader impact of PCr on patient recovery and quality of life post-treatment.

The clinical trial involved a total of **50 participants** who were selected based on specific inclusion criteria. The study population comprised both **male and female** subjects, aged 18 years and older, who were admitted to the hospital but not in the intensive care unit (ICU). Participants were required to provide written informed consent, either personally or through a legal representative. The trial focused on individuals with impending or underlying cardiac failure or cardiac arrest, with the Medical Emergency Team (MET) being called upon for conditions such as **tachypnea**, **tachycardia**, and a systolic blood pressure of less than 90 mmHg, among others. The participants were required to have a serum creatinine level of 2 mg/dl or less. The trial population included a vulnerable group, reflecting the serious nature of the medical conditions under investigation. Lifestyle factors such as diet and physical activity were not specified in the trial data provided.

The clinical trial is designed to evaluate the effect of **phosphocreatine sodium** on patients treated by a medical emergency team. This is a randomized, double-blind, controlled trial comparing the experimental group receiving phosphocreatine sodium with a control group receiving a placebo, specifically a saline solution. The primary objective is to assess the number of days alive and out of the hospital at 30 days (DAOH30). The trial is expected to commence recruitment on October 8, 2024, and conclude by May 31, 2027. Participants will be involved in the study for a maximum treatment period of three days, with the possibility of early termination if they no longer meet the inclusion criteria or if adverse events occur.

The trial will include several study visits, beginning with a screening visit to confirm eligibility based on criteria such as age, serum creatinine levels, and specific medical conditions like tachypnea, tachycardia, and threatened airways. Following randomization, participants will receive either the active treatment or placebo via infusion. Follow-up visits will be scheduled to monitor the participants' health status and collect data on the primary endpoint. The end-of-study visit will occur at the conclusion of the treatment period or upon early termination, during which final assessments will be conducted.

Inclusion criteria require participants to be hospitalized outside the ICU, aged 18 years or older, and to provide written informed consent. Exclusion criteria are not specified in the provided data. The trial's primary endpoint is the calculation of DAOH30, which involves assessing whether the patient has died in the hospital or after discharge within the first 30 days post-randomization. Secondary endpoints are not detailed in the available information. The trial is categorized as a confirmatory Phase III clinical trial, indicating its focus on confirming the efficacy and safety of the intervention in a larger patient population.

The clinical trial involves the administration of **phosphocreatine sodium** as the experimental medication. The product, marketed under the name Neoton Phlebo 1 g, is provided in the form of a **solution for infusion**. The active substance, phosphocreatine sodium, is of chemical origin. The maximum daily dose is 8 grams, with a total maximum dose of 16 grams over the treatment period. The medication is administered via infusion, with a maximum treatment period of 3 days. The product is manufactured by ALFASIGMA S.P.A. and is not a pediatric formulation.

The comparator treatment in this study is a **sodium chloride** solution, marketed as Sodio cloruro Fresenius Kabi Italia 0.9%. This solution is also provided as a **solution for infusion** and serves as the placebo in the trial. The active substance, sodium chloride, is of chemical origin. The maximum daily dose is 400 milliliters, with a total maximum dose of 1.2 liters over the treatment period. This solution is administered via infusion, with a maximum treatment period of 3 days. The product is manufactured by FRESENIUS KABI ITALIA S.R.L. and is not a pediatric formulation.

Efficacy in the clinical trial titled "The effect of phosphocreatine on medical emergency team treated patients: a randomized clinical trial protocol – SPHERE" will be assessed by comparing the effect of **phosphocreatine** (PCr) with a placebo (saline solution) on the primary endpoint, which is the number of days alive and out of hospital at 30 days (DAOH30). The primary endpoint will be calculated by determining if the patient has died in the hospital or after discharge within the first 30 days after randomization. If the patient has died, 0 points will be assigned. If the patient is discharged from the hospital on Day 5 after randomization but is subsequently readmitted for 5 days before their second hospital discharge, 20 points will be assigned. Days spent in a post-discharge nursing facility will not be considered as days at home.