Ischaemic PReconditioning In Non Cardiac surgEry

NCT ID: NCT02427867

Last Updated: 2025-08-07

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 1217 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2025-12-31

Brief 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 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

remote ischemic preconditioning

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.

Group Type: EXPERIMENTAL

Remote ischemic preconditioning

Intervention Type: OTHER

no ischemic preconditioning

The cuff will be placed around the arm but not inflated.

Group Type: PLACEBO_COMPARATOR

no ischemic preconditioning

Intervention Type: OTHER

Interventions

Remote ischemic preconditioning

Intervention Type: OTHER

no ischemic preconditioning

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• written informed consent
• intermedial and high risk non cardiac surgery
• general anesthesia
• ongoing or recently suspended antiplatelet therapy

Exclusion Criteria

• 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

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Università Vita-Salute San Raffaele

OTHER

Sponsor Role: lead

Responsible Party

Giovanni Landoni

MD, Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alberto Zangrillo, Prof.

Role: STUDY_CHAIR

Vita-Salute University of Milan

Locations

Xijing Hospital

Xi'an, , China

Fundación Cardioinfantil-Instituto de Cardiología

Bogotá, , Colombia

University Hospital Centre Zagreb

Zagreb, , Croatia

Humanitas Clinical Institute

Rozzano, Lombardy, Italy

Valle Olona Po hospital

Busto Arsizio, Varese, Italy

Ospedale Cardinal Massaia

Asti, , Italy

Azienda Ospedaliero Universitaria Careggi

Florence, , Italy

E.O. Ospedali Galliera

Genova, , Italy

IRCCS San Raffaele Scientific Institute

Milan, , Italy

Fondazione IRCCS. Istituto Neurologico Carlo Besta

Milan, , Italy

Università degli studi della Campania Luigi Vanvitelli

Napoli, , Italy

Azienda Universitaria Ospedaliero Pisana

Pisa, , Italy

A.O.U. Pisana

Pisa, , Italy

Fondazione Policlinico Universitario Campus Bio-Medico di Roma

Rome, , Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, , Italy

ULSS 4 Veneto Orientale, Ospedale di San Donà di Piave

San Donà di Piave, , Italy

Azienda Sanitaria Universitaria Friuli Centrale "Santa Maria della Misericordia"

Udine, , Italy

Astana Medical University

Astana, , Kazakhstan

Loginov Moscow Clinical Scientific Center

Moscow, , Russia

Oncological Center No. 1 of the S. S. Yudin City Clinical Hospital of the Moscow Department of Health

Moscow, , Russia

I.M. Sechenov First Moscow State Medical

Moscow, , Russia

V.Negovsky Reanimatolgy Research Institute

Moscow, , Russia

Saint-Petersburg State University Hospital

Saint Petersburg, , Russia

Institute of Cardiovascular Diseases "Dedinje"

Belgrade, , Serbia

National University Hospital

Singapore, , Singapore

Ospedale Regionale di Lugano

Lugano, , Switzerland

Countries

China; Colombia; Croatia; Italy; Kazakhstan; Russia; Serbia; Singapore; Switzerland

References

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

Reference Type: BACKGROUND

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.

Reference Type: DERIVED

PMID: 40511609 (View on PubMed)

Liang 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.

Reference Type: DERIVED

PMID: 36645250 (View on PubMed)

Other Identifiers

PRINCE/43/OSR

Identifier Type: -

Identifier Source: org_study_id