HypotensionPhase 3SPHERENCT06503016
The Effect of phoSPHocreatine on mEdical Emergency Team (Met) tREated Patients
A Phase 3 study testing Phosphocreatine in people with Hypotension and Consciousness, Level Altered, run by Università Vita-Salute San Raffaele at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypotension, Consciousness, Level Altered, Airway Disease
- What is being tested?
- Phosphocreatine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 400 participants
- Where
- 1 siteItaly
- Study dates
- 8 Oct 2024to Jul 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
IRCCS San Raffaele Scientific Institute
Milan, 20132
Giovanni Landoni, Prof, landoni.giovanni@hsr.it
Silvia Ajello, MD
About this study
Official title: The Effect of phoSPHocreatine on mEdical Emergency Team (Met) tREated Patients: a Randomized Clinical Trial Protocol
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
- Being tested
- Phosphocreatine, Placebo
- Medical subject headings
- Hypotension, Consciousness Disorders, Respiratory Insufficiency, Tachypnea, Hypoventilation, Tachycardia, Bradycardia, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PhosphocreatineDrug
Administration of Phosphocreatine
PlaceboDrug
Saline solution of NaCl 0.9%
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: day 30 or hospital discharge
Secondary outcomes (5)
Cognitive function
Evaluation of cognitive function using the Cognitive Telephone Screening Instrument (COGTEL). The COGTEL is a test that evaluates the cognitive performance of survived patients 30 days after randomization. This scale has a minimum of zero points and a maximum of 100.
Measured: day 30
Rate of arrhythmia needing treatment
Clinically relevant arrhythmias will be recorded and confirmed by an ECG. Rate of major arrhythmias divided into supraventricular arrhythmias, ventricular arrhythmias, bradyarrhythmias, and need for antiarrhythmics will be registered.
Measured: hospital discharge (which usually occurs in the 30days after randomization)
Rate of ICU admissions or criteria for ICU admission
ICU admission
Measured: hospital discharge (which usually occurs in the 30days after randomization)
Death at 30 days
Death
Measured: day 30
Death at 90 days
Death
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2024
- Study start8 Oct 2024
- Primary completionApr 2026 (estimated)
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HypotensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Università Vita-Salute San Raffaele
- Sponsor type
- University, hospital or other
- Collaborators
- Silvia Ajello
- Responsible party
- Principal investigator, Giovanni Landoni, Università Vita-Salute San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06503016
- Sponsor's protocol ID
- GR-2021-12375001
- Acronym
- SPHERE
- Status last verified
- Aug 2025
- First submitted
- 5 Jul 2024
- Last updated
- 6 Aug 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 27318357Mingxing 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.
PubMed 29409711
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of phoSPHocreatine on mEdical Emergency Team (Met) tREated Patients: a Randomized Clinical Trial Protocol
- ClinicalTrials.gov ID
- NCT06503016
- Acronym / sponsor ID
- SPHERE / GR-2021-12375001
- Conditions
- Hypotension, Consciousness, Level Altered, Airway Disease, Respiratory Failure, Tachypnea, Bradypnea
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Università Vita-Salute San RaffaeleUniversity, hospital or other
- Collaborators
- Silvia Ajello
- Study start
- 8 Oct 2024 (actual)
- Primary completion
- Apr 2026 (estimated)
- Study completion
- Jul 2026 (estimated)
- First posted
- 16 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phosphocreatine | Experimental | Drug: PhosphocreatinePatients 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. |
| Placebo | Placebo comparator | Drug: PlaceboPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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:
Key exclusion criteria (13 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PhosphocreatineAdministration of Phosphocreatine | Drug | Phosphocreatine |
| PlaceboSaline solution of NaCl 0.9% | Drug | Placebo |
Primary outcome
days alive and out of hospital at 30 days.
Time frame: day 30 or hospital discharge
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.
5 secondary outcomes
Cognitive function
Time frame: day 30
Rate of arrhythmia needing treatment
Time frame: hospital discharge (which usually occurs in the 30days after randomization)
Rate of ICU admissions or criteria for ICU admission
Time frame: hospital discharge (which usually occurs in the 30days after randomization)
Death at 30 days
Time frame: day 30
Death at 90 days
Time frame: 90 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2025.
- Background: PubMed 27318357Landoni 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.
- Background: PubMed 29409711Mingxing 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Phosphocreatine in people with Hypotension and Consciousness, Level Altered, run by Università Vita-Salute San Raffaele at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Giovanni Landoni, Prof. (+39022643 ext. 6151, landoni.giovanni@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
days alive and out of hospital at 30 days. (time frame: day 30 or hospital discharge). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06503016, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2025.