The Effect of phoSPHocreatine on mEdical Emergency Team (Met) tREated Patients

NCT06503016 | Recruiting Phase 3

• 1 other identifier: GR-2021-12375001
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

Unexpected deaths and unplanned intensive care unit (ICU) admissions are common during hospital stay and are often preceded by warning abnormalities in patients' vital signs. These abnormalities trigger Medical Emergency Team (MET) activation and up to 15% of patients visited by the MET is admitted to the ICU with an overall hospital stay after the MET intervention of approximately 2 weeks. Phosphocreatine (PCr) is a natural energy-buffering molecule associated with signals of mortality reduction in patients with acute cardiac conditions (according to meta-analytic finding from our group) and with encouraging beneficial effects on other acute organ failures (e.g. brain). The investigators designed a multi-center, randomized, placebo-controlled trial to confirm the promising beneficial effects of PCr in hospitalized patients. The investigators expects a reduction in hospital stay (measured as an increase in days alive and out of hospital at 30 days) when PCr is added to standard treatment in patients requiring MET intervention.

Conditions

Hypotension; Consciousness, Level Altered; Airway Disease; Respiratory Failure; Tachypnea; Bradypnea; Tachycardia; Bradycardia; Cardiac Failure; Cardiac Arrest

Outcome Measures

Primary Outcomes (1)

• days alive and out of hospital at 30 days.

  To compare the effect of phosphocreatine (PCr) (experimental group), versus placebo (saline solution-control group) on the number of days alive and out of hospital at 30 days.

  day 30 or hospital discharge

Secondary Outcomes (5)

• Cognitive function

  day 30

• Rate of arrhythmia needing treatment

  hospital discharge (which usually occurs in the 30days after randomization)

• Rate of ICU admissions or criteria for ICU admission

  hospital discharge (which usually occurs in the 30days after randomization)

• Death at 30 days

  day 30

• Death at 90 days

  90 days

Study Arms (2)

Phosphocreatine

EXPERIMENTAL

Patients randomized to the phosphocreatine group will receive the drug for a maximum of 3 days. * Patients without renal failure: At the time of randomization (day 0), 4 grams of phosphocreatine will be administered, followed by an additional 4 grams on the same day, with a minimum interval of 20 minutes and a maximum of 4 hours. On day 1 and day 2, after 8 AM, 2 grams of phosphocreatine will be administered twice a day, with a 6-hour interval between doses. * Patients with history of renal failure: On day 0, patients will receive a single dose of 4 grams of phosphocreatine. On day 1 and day 2, after 8 AM, 2 grams of phosphocreatine will be administered twice a day, with a 6-hour interval between doses. * Patients with acute kidney injury, without chronic kidney disease: Single dose of 4 grams of phosphocreatine on day 0. No further doses of the drug are planned.

Drug: Phosphocreatine

Placebo

PLACEBO COMPARATOR

Patients randomized to the placebo group will receive saline solution for a maximum of 3 days. * Patients without renal failure: 200 ml of saline solution twice a day from day 0 to day 2. On day 0, the second bolus should be administered between 20 minutes and 4 hours after the first bolus; on day 1 and day 2, the saline solution should be administered after 8 AM, with the second bolus given 6 hours later. * Patients with history of renal failure: On day 0, a single infusion of 200 mL of saline solution will be administered. On day 1 and day 2, 200 mL of saline solution will be administered twice a day, after 8 AM, with a 6-hour interval between doses. * Patients with acute kidney injury, without chronic kidney disease: A single infusion of 200 mL of saline solution on day 0. No further administrations are planned.

Drug: Placebo

Interventions

Phosphocreatine DRUG

Administration of Phosphocreatine

Phosphocreatine

Placebo DRUG

Saline solution of NaCl 0.9%

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Admitted in hospital (but outside ICU)
• Age\>=18 years
• Written informed consent
• Serum creatinine \<=2 mg/dl
• Patient with impending or underlying cardiac failure or cardiac arrest, irrespectively of the primitive organ failure, and the Medical Emergency Team (MET) is called upon at least one of the following:
• Threatened airways;
• Respiratory arrest;
• Respiratory rate \<5 or \>36 breaths per min;
• Pulse rate \<40 or \>140 beats per min;
• Systolic blood pressure \< 90 mm Hg;
• Sudden fall in level of consciousness;
• Fall in Glasgow coma scale of \> 2 points.

You may not qualify if:

• Age \< 18 years;
• Ongoing cardiac massage;
• Current hospital admission from a care nursing facility;
• Planned discharge to a care nursing facility;
• Reasons for withdrawal of life-sustaining therapy;
• History of kidney transplantation;
• Solitary kidney (by any reason);
• Serum Creatinine \> 2 mg/dl;
• Immediate need for ICU admission;
• Known allergy to PCr;
• Pregnancy;
• Previous enrollment and randomization into this trial;
• Administration of PCr in the previous 30 day.

Sponsors & Collaborators

• Università Vita-Salute San Raffaele: lead
• Silvia Ajello: collaborator

Study Sites (1)

IRCCS San Raffaele Scientific Institute

Milan, 20132, Italy

RECRUITING

Related Publications (2)

• Landoni G, Zangrillo A, Lomivorotov VV, Likhvantsev V, Ma J, De Simone F, Fominskiy E. Cardiac protection with phosphocreatine: a meta-analysis. Interact Cardiovasc Thorac Surg. 2016 Oct;23(4):637-46. doi: 10.1093/icvts/ivw171. Epub 2016 Jun 17.

  PMID: 27318357 BACKGROUND

• Mingxing F, Landoni G, Zangrillo A, Monaco F, Lomivorotov VV, Hui C, Novikov M, Nepomniashchikh V, Fominskiy E. Phosphocreatine in Cardiac Surgery Patients: A Meta-Analysis of Randomized Controlled Trials. J Cardiothorac Vasc Anesth. 2018 Apr;32(2):762-770. doi: 10.1053/j.jvca.2017.07.024. Epub 2017 Jul 24.

  PMID: 29409711 BACKGROUND

MeSH Terms

Conditions

Hypotension; Consciousness Disorders; Respiratory Insufficiency; Tachypnea; Hypoventilation; Tachycardia; Bradycardia; Heart Failure; Heart Arrest

Interventions

Phosphocreatine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Arrhythmias, Cardiac; Heart Diseases; Cardiac Conduction System Disease; Pathologic Processes

Intervention Hierarchy (Ancestors)

Creatine; Amino Acids; Amino Acids, Peptides, and Proteins; Phosphoamino Acids

Central Study Contacts

Giovanni Landoni, Prof.

CONTACT

+39022643; landoni.giovanni@hsr.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Full Professor

Study Record Dates

• First Submitted: July 5, 2024
• First Posted: July 16, 2024
• Study Start: October 8, 2024
• Primary Completion: April 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: August 6, 2025

Record last verified: 2025-08

Locations

IT (1)