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

Università Vita-Salute San Raffaele

Status and phase: Enrolling; Phase 3

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

Treatments: Drug: Phosphocreatine; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT06503016

GR-2021-12375001

Details and patient eligibility

About

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.

Enrollment: 400 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Admitted in hospital (but outside ICU)

2. Age>=18 years

3. Written informed consent

4. Serum creatinine <=2 mg/dl

5. 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:

   1. Threatened airways;
   2. Respiratory arrest;
   3. Respiratory rate <5 or >36 breaths per min;
   4. Pulse rate <40 or >140 beats per min;
   5. Systolic blood pressure < 90 mm Hg;
   6. Sudden fall in level of consciousness;
   7. Fall in Glasgow coma scale of > 2 points.

Exclusion criteria

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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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400 participants in 2 patient groups, including a placebo group

Phosphocreatine

Experimental group

Description:

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.

Treatment:

Drug: Phosphocreatine

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo