Myocardial IschemiaPRINCENCT02427867
Ischaemic PReconditioning In Non Cardiac surgEry
A study testing Remote ischemic preconditioning and no ischemic preconditioning in people with Myocardial Ischemia and Surgery, run by Università Vita-Salute San Raffaele at 26 sites in 9 countries.
Trial summary
Several randomized trials suggested a cardioprotective beneficial effect (eg reduction in cardiac troponin release) of remote ischemic preconditioning in cardiac surgery. Remote ischemic preconditioning by brief episodes of ischemia and reperfusion in a remote organ or vascular territory provides protection from… Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Myocardial Ischemia, Surgery
- What is being tested?
- Remote ischemic preconditioning and no ischemic preconditioning
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,217 participants
- Where
- 26 sitesin 9 countries
- Study dates
- Apr 2015to Dec 2026
- Phase
- Interventional
- 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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- written informed consent
- intermedial and high risk non cardiac surgery
- general anesthesia
- ongoing or recently suspended antiplatelet therapy
Who cannot join
- pregnancy
- planned locoregional anesthesia without general anesthesia
- unstable or ongoing angina
- recent (< 1 month) or ongoing acute myocardial infarction
- inclusion in other randomised controlled studies in the previous 30 days
- peripheral vascular disease affecting the upper limbs
- cardiac surgery
Trial locations and contacts
26 sites in 9 countries.
26 sites in 9 countries
Italy14 sites
Ospedale Cardinal Massaia
Asti, 14100
Valle Olona Po hospital
Busto Arsizio, Varese
Azienda Ospedaliero Universitaria Careggi
Florence, 50139
E.O. Ospedali Galliera
Genova, 16128
IRCCS San Raffaele Scientific Institute
Milan, 20132
Fondazione IRCCS. Istituto Neurologico Carlo Besta
Milan, 20133
Università degli studi della Campania Luigi Vanvitelli
Naples, 80138
Azienda Universitaria Ospedaliero Pisana
Pisa, 56100
A.O.U. Pisana
Pisa
Fondazione Policlinico Universitario Campus Bio-Medico di Roma
Rome, 00128
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Rome, 00136
Humanitas Clinical Institute
Rozzano, Lombardy, 20100
ULSS 4 Veneto Orientale, Ospedale di San Donà di Piave
San Donà di Piave, 30027
Azienda Sanitaria Universitaria Friuli Centrale "Santa Maria della Misericordia"
Udine, 33100
Russia5 sites
Loginov Moscow Clinical Scientific Center
Moscow, 111123
Oncological Center No. 1 of the S. S. Yudin City Clinical Hospital of the Moscow Department of Health
Moscow, 117152
I.M. Sechenov First Moscow State Medical
Moscow
V.Negovsky Reanimatolgy Research Institute
Moscow
Saint-Petersburg State University Hospital
Saint Petersburg
Colombia1 site
Fundación Cardioinfantil-Instituto de Cardiología
Bogotá, 110131
About this study
Several randomized trials suggested a cardioprotective beneficial effect (eg reduction in cardiac troponin release) of remote ischemic preconditioning in cardiac surgery.
Remote ischemic preconditioning by brief episodes of ischemia and reperfusion in a remote organ or vascular territory provides protection from injury by myocardial ischemia and reperfusion. In the translation of remote ischemic preconditioning from bench to bedside, the first proof of principle and small randomized controlled trials have shown a decreased release of myocardial biomarkers after aortic, congenital cardiac, adult valve and coronary artery by-pass graft surgery. This reduction in cardiac biomarkers release translated into better survival in a recent randomized trial performed in cardiac surgery. No clinical trial on remote ischemic preconditioning in non-cardiac surgery setting has been performed so far.
The investigators study wants to test, for the first time, the hypothesis that remote ischaemic preconditioning is effective in reducing cardiac damage in high risk patients undergoing non-cardiac surgery. Remote ischaemic preconditioning will be achieved by inflation of a blood-pressure cuff to 200 mm Hg to the upper arm for 5 minutes, followed by 5 minutes reperfusion while the cuff will be deflated. General anesthesia will be induced and maintained without using propofol in both groups. Cardiac troponin will be used as marker of cardiac damage. If the results of a reduction in postoperative cardiac troponin release and perioperative cardiac ischaemic events will be confirmed in a non-cardiac surgery setting, the investigators could improve a strategy to prevent perioperative cardiac complication easy to apply, safe and low cost.
- Conditions
- Myocardial Ischemia, Surgery
- Being tested
- Remote ischemic preconditioning, no ischemic preconditioning
- Keywords
- remote ischemic preconditioning, non cardiac surgery, myocardial ischemia
- Medical subject headings
- Myocardial Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remote ischemic preconditioningOther
no ischemic preconditioningOther
| Study group | Role | What they receive |
|---|---|---|
| remote ischemic preconditioning | Experimental | Three cycles of 5 minutes ischemia will be applied to the upper left arm (or right arm or legs if the left arm will not be deemed suitable by the attending physician), achieved by inflation of a blood-pressure cuff to 200 mm Hg, followed by 5 minutes reperfusion while the cuff will be deflated. Receives: Other: Remote ischemic preconditioning |
| no ischemic preconditioning | Placebo comparator | The cuff will be placed around the arm but not inflated. Receives: Other: no ischemic preconditioning |
What is being measured
The primary outcome is the main question the study is designed to answer.
cardiac troponin
elevation of cardiac troponin after non-cardiac surgery
Measured: Hospital - approximately 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2015 (estimated)
- Study startApr 2015
- Primary completionJan 2025
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Myocardial IschemiaStudies 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,217 participants (actual)
Sponsor and investigators
- Lead sponsor
- Università Vita-Salute San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giovanni Landoni, Università Vita-Salute San Raffaele
- Investigators
- Alberto Zangrillo, Prof., Study chair, Vita-Salute University of Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02427867
- Sponsor's protocol ID
- PRINCE/43/OSR
- Acronym
- PRINCE
- Status last verified
- May 2026
- First submitted
- 15 Apr 2015
- Last updated
- 11 May 2026
- Results posted
- No
Publications
Massimiliano Greco, Gaetano Lombardi, Aidos Konkayev, Claudia Brusasco, Chong Lei, Agostino Roasio, Nerlep Rana, Hugo A. Mantilla-gutierrez, Marco Micali, Gordana Gazivoda, Michela Gandini, Lian Kah Ti, Stefano Bosso, Maiya Konkayeva, Francesco Meroi, Lini Wang, Andrea Russo, Sergey Efremov, Giuseppe Fresta, Levan Berikashvili, Francesca Livi, Ivan Šitum, Fabio Guarracino, Elizaveta Leonova, Francesca Cavenago, Maria Shemetova, Edoardo Cristallo, Anastasia Smirnova, Lorenzo Schiavoni, Valerii Subbotin, Nicoletta Boffa, Giuseppe Giardina, Michele Introna, Cristina Nakhnoukh, Remo Daniel Covello, Marina Pieri, Stefano Turi, Valentina Ajello, Fabrizio Monaco, Francesco Corradi, Andrey Yavorovskiy, Valery Likhvantsev, Federico Longhini, Tiziana Bove, Rinaldo Bellomo, Giovanni Landoni, Alberto Zangrillo, Rosalba Lembo. Remote ischemic preconditioning in non-cardiac surgery (PRINCE): a multinational, double blind, sham-controlled, randomized clinical trial. Signa Vitae. 2024. 20(12);1-9. https://www.signavitae.com/articles/10.22514/sv.2024.151
Greco M, Lombardi G, Brusasco C, Pieri M, Roasio A, Monaco F, Berikashvili L, Belletti A, Meroi F, Fresilli S, Kabibulatov A, Giardina G, Russo A, Oliva FM, Efremov S, Lembo R, Wang L, Vietri S, Momesso E, D'Amico F, Kadantseva K, Labanca R, Ryzhkov P, Marmiere M, Subbotin V, Pruna A, Rana N, Livi F, Mantilla-Gutierrez H, Guarracino F, Schiavoni L, Situm I, Micali M, Bosso S, Smirnova A, Fresta G, Cherednichenko A, Beretta L, Monti G, Ti LK, Sansone P, Corradi F, Cecconi M, Yavorovskiy A, Lei C, Konkayev A, Bove T, Likhvantsev V, Zangrillo A, Landoni G, Bellomo R, Covello RD, Turi S; PRINCE Study Group. Effect of Remote Ischemic Preconditioning on Myocardial Injury in Noncardiac Surgery: The PRINCE Randomized Clinical Trial. Circulation. 2025 Oct 28;152(17):1194-1205. doi: 10.1161/CIRCULATIONAHA.125.075254. Epub 2025 Jun 13.
PubMed 40511609Liang F, Liu S, Liu G, Liu H, Wang Q, Song B, Yao L. Remote ischaemic preconditioning versus no remote ischaemic preconditioning for vascular and endovascular surgical procedures. Cochrane Database Syst Rev. 2023 Jan 16;1(1):CD008472. doi: 10.1002/14651858.CD008472.pub3.
PubMed 36645250
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ischaemic PReconditioning In Non Cardiac surgEry
- ClinicalTrials.gov ID
- NCT02427867
- Acronym / sponsor ID
- PRINCE / PRINCE/43/OSR
- Conditions
- Myocardial Ischemia, Surgery
- Keywords
- remote ischemic preconditioning, non cardiac surgery, myocardial ischemia
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 1,217 participants (actual)
- Lead sponsor
- Università Vita-Salute San RaffaeleUniversity, hospital or other
- Study start
- Apr 2015 (actual)
- Primary completion
- Jan 2025 (actual)
- Study completion
- Dec 2026 (estimated)
- First posted
- 28 Apr 2015 (estimated)
- 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.
Several randomized trials suggested a cardioprotective beneficial effect (eg reduction in cardiac troponin release) of remote ischemic preconditioning in cardiac surgery.
Remote ischemic preconditioning by brief episodes of ischemia and reperfusion in a remote organ or vascular territory provides protection from injury by myocardial ischemia and reperfusion. In the translation of remote ischemic preconditioning from bench to bedside, the first proof of principle and small randomized controlled trials have shown a decreased release of myocardial biomarkers after aortic, congenital cardiac, adult valve and coronary artery by-pass graft surgery. This reduction in cardiac biomarkers release translated into better survival in a recent randomized trial performed in cardiac surgery. No clinical trial on remote ischemic preconditioning in non-cardiac surgery setting has been performed so far.
The investigators study wants to test, for the first time, the hypothesis that remote ischaemic preconditioning is effective in reducing cardiac damage in high risk patients undergoing non-cardiac surgery. Remote ischaemic preconditioning will be achieved by inflation of a blood-pressure cuff to 200 mm Hg to the upper arm for 5 minutes, followed by 5 minutes reperfusion while the cuff will be deflated. General anesthesia will be induced and maintained without using propofol in both groups. Cardiac troponin will be used as marker of cardiac damage. If the results of a reduction in postoperative cardiac troponin release and perioperative cardiac ischaemic events will be confirmed in a non-cardiac surgery setting, the investigators could improve a strategy to prevent perioperative cardiac complication easy to apply, safe and low cost.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| remote ischemic preconditioning | Experimental | Other: Remote ischemic preconditioningThree cycles of 5 minutes ischemia will be applied to the upper left arm (or right arm or legs if the left arm will not be deemed suitable by the attending physician), achieved by inflation of a blood-pressure cuff to 200 mm Hg, followed by 5 minutes reperfusion while the cuff will be deflated. |
| no ischemic preconditioning | Placebo comparator | Other: no ischemic preconditioningThe cuff will be placed around the arm but not inflated. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- written informed consent
- intermedial and high risk non cardiac surgery
- general anesthesia
- ongoing or recently suspended antiplatelet therapy
Key exclusion criteria (7 listed)
- pregnancy
- planned locoregional anesthesia without general anesthesia
- unstable or ongoing angina
- recent (< 1 month) or ongoing acute myocardial infarction
- inclusion in other randomised controlled studies in the previous 30 days
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 |
|---|---|---|
| Remote ischemic preconditioning | Other | remote ischemic preconditioning |
| no ischemic preconditioning | Other | no ischemic preconditioning |
Primary outcome
cardiac troponin
Time frame: Hospital - approximately 1 week
elevation of cardiac troponin after non-cardiac surgery
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 11 May 2026.
- BackgroundMassimiliano Greco, Gaetano Lombardi, Aidos Konkayev, Claudia Brusasco, Chong Lei, Agostino Roasio, Nerlep Rana, Hugo A. Mantilla-gutierrez, Marco Micali, Gordana Gazivoda, Michela Gandini, Lian Kah Ti, Stefano Bosso, Maiya Konkayeva, Francesco Meroi, Lini Wang, Andrea Russo, Sergey Efremov, Giuseppe Fresta, Levan Berikashvili, Francesca Livi, Ivan Šitum, Fabio Guarracino, Elizaveta Leonova, Francesca Cavenago, Maria Shemetova, Edoardo Cristallo, Anastasia Smirnova, Lorenzo Schiavoni, Valerii Subbotin, Nicoletta Boffa, Giuseppe Giardina, Michele Introna, Cristina Nakhnoukh, Remo Daniel Covello, Marina Pieri, Stefano Turi, Valentina Ajello, Fabrizio Monaco, Francesco Corradi, Andrey Yavorovskiy, Valery Likhvantsev, Federico Longhini, Tiziana Bove, Rinaldo Bellomo, Giovanni Landoni, Alberto Zangrillo, Rosalba Lembo. Remote ischemic preconditioning in non-cardiac surgery (PRINCE): a multinational, double blind, sham-controlled, randomized clinical trial. Signa Vitae. 2024. 20(12);1-9. https://www.signavitae.com/articles/10.22514/sv.2024.151
- Derived from this study: PubMed 40511609Greco M, Lombardi G, Brusasco C, Pieri M, Roasio A, Monaco F, Berikashvili L, Belletti A, Meroi F, Fresilli S, Kabibulatov A, Giardina G, Russo A, Oliva FM, Efremov S, Lembo R, Wang L, Vietri S, Momesso E, D'Amico F, Kadantseva K, Labanca R, Ryzhkov P, Marmiere M, Subbotin V, Pruna A, Rana N, Livi F, Mantilla-Gutierrez H, Guarracino F, Schiavoni L, Situm I, Micali M, Bosso S, Smirnova A, Fresta G, Cherednichenko A, Beretta L, Monti G, Ti LK, Sansone P, Corradi F, Cecconi M, Yavorovskiy A, Lei C, Konkayev A, Bove T, Likhvantsev V, Zangrillo A, Landoni G, Bellomo R, Covello RD, Turi S; PRINCE Study Group. Effect of Remote Ischemic Preconditioning on Myocardial Injury in Noncardiac Surgery: The PRINCE Randomized Clinical Trial. Circulation. 2025 Oct 28;152(17):1194-1205. doi: 10.1161/CIRCULATIONAHA.125.075254. Epub 2025 Jun 13.
- Derived from this study: PubMed 36645250Liang F, Liu S, Liu G, Liu H, Wang Q, Song B, Yao L. Remote ischaemic preconditioning versus no remote ischaemic preconditioning for vascular and endovascular surgical procedures. Cochrane Database Syst Rev. 2023 Jan 16;1(1):CD008472. doi: 10.1002/14651858.CD008472.pub3.
Related trials for Myocardial Ischemia
Not yet recruiting
GOT VOICE Feasibility With In-Person Group Singing
Elderly, Coronary Arterial Disease (CAD)
RecruitingObservational study
Real-life Registry in Patients With Coronary Artery Disease Treated With the SELUTION Sirolimus-eluting Balloon. Selution Iberia Registry
Cardiovascular Diseases
Recruiting
Lifewise Preventive Video Education in Primary Care
Prevention Harmful Effects, Health Maintenance
RecruitingPhase 4
Inclisiran Versus Placebo for the Prevention of Major Adverse Cardiovascular and Limb Events in Patients Undergoing Percutaneous Coronary Intervention or Peripheral Endovascular Intervention
Percutaneous Coronary Intervention, Peripheral Endovascular Intervention
Active, not recruiting
Comparison of Vessel-FFR Versus FFR in Intermediate Coronary Stenoses
Coronary Artery Disease, Coronary Artery Stenoses
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. This study is not recruiting at the moment.
Alberto Zangrillo, Prof. study chair
Vita-Salute University of Milan
26 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Remote ischemic preconditioning and no ischemic preconditioning in people with Myocardial Ischemia and Surgery, run by Università Vita-Salute San Raffaele at 26 sites in 9 countries.
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 4 inclusion and 7 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: under way, not looking for participants, as of the sponsor's last update on 11 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in Italy, Russia, China, Colombia, Croatia and 4 more countries. 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.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
cardiac troponin (time frame: Hospital - approximately 1 week). 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 NCT02427867, which also lists 3 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 11 May 2026.