NCT02427867

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.

Trial Health

62
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
1,217

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Apr 2015

Longer than P75 for not_applicable

Geographic Reach
9 countries

26 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2015

Completed
14 days until next milestone

First Submitted

Initial submission to the registry

April 15, 2015

Completed
13 days until next milestone

First Posted

Study publicly available on registry

April 28, 2015

Completed
9.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2025

Completed
11 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2025

Completed
Last Updated

August 7, 2025

Status Verified

August 1, 2025

Enrollment Period

9.8 years

First QC Date

April 15, 2015

Last Update Submit

August 5, 2025

Conditions

Myocardial IschemiaSurgery

Keywords

remote ischemic preconditioningnon cardiac surgerymyocardial ischemia

Outcome Measures

Primary Outcomes (1)

  • cardiac troponin

    elevation of cardiac troponin after non-cardiac surgery

    Hospital - approximately 1 week

Study Arms (2)

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.

Other: Remote ischemic preconditioning

no ischemic preconditioning

PLACEBO COMPARATOR

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

Other: no ischemic preconditioning

Interventions

Remote ischemic preconditioningOTHER
remote ischemic preconditioning
no ischemic preconditioningOTHER
no ischemic preconditioning

Eligibility Criteria

Age50 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • pregnancy
  • planned locoregional anesthesia without general anesthesia
  • unstable or ongoing angina
  • recent (\< 1 month) or ongoing acute myocardial infarction
  • peripheral vascular disease affecting the upper limbs
  • cardiac surgery

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (26)

Xijing Hospital

Xi'an, 710032, China

Location

Fundación Cardioinfantil-Instituto de Cardiología

Bogotá, 110131, Colombia

Location

University Hospital Centre Zagreb

Zagreb, 10000, Croatia

Location

Humanitas Clinical Institute

Rozzano, Lombardy, 20100, Italy

Location

Valle Olona Po hospital

Busto Arsizio, Varese, Italy

Location

Ospedale Cardinal Massaia

Asti, 14100, Italy

Location

Azienda Ospedaliero Universitaria Careggi

Florence, 50139, Italy

Location

E.O. Ospedali Galliera

Genova, 16128, Italy

Location

IRCCS San Raffaele Scientific Institute

Milan, 20132, Italy

Location

Fondazione IRCCS. Istituto Neurologico Carlo Besta

Milan, 20133, Italy

Location

Università degli studi della Campania Luigi Vanvitelli

Napoli, 80138, Italy

Location

Azienda Universitaria Ospedaliero Pisana

Pisa, 56100, Italy

Location

A.O.U. Pisana

Pisa, Italy

Location

Fondazione Policlinico Universitario Campus Bio-Medico di Roma

Rome, 00128, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, 00136, Italy

Location

ULSS 4 Veneto Orientale, Ospedale di San Donà di Piave

San Donà di Piave, 30027, Italy

Location

Azienda Sanitaria Universitaria Friuli Centrale "Santa Maria della Misericordia"

Udine, 33100, Italy

Location

Astana Medical University

Astana, 010000, Kazakhstan

Location

Loginov Moscow Clinical Scientific Center

Moscow, 111123, Russia

Location

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

Moscow, 117152, Russia

Location

I.M. Sechenov First Moscow State Medical

Moscow, Russia

Location

V.Negovsky Reanimatolgy Research Institute

Moscow, Russia

Location

Saint-Petersburg State University Hospital

Saint Petersburg, Russia

Location

Institute of Cardiovascular Diseases "Dedinje"

Belgrade, Serbia

Location

National University Hospital

Singapore, 119074, Singapore

Location

Ospedale Regionale di Lugano

Lugano, Switzerland

Location

Related Publications (3)

  • 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

    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.

    PMID: 40511609DERIVED

  • 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.

    PMID: 36645250DERIVED

MeSH Terms

Conditions

Myocardial Ischemia

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular DiseasesVascular Diseases

Study Officials

  • Alberto Zangrillo, Prof.

    Vita-Salute University of Milan

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, Associate Professor

Study Record Dates

First Submitted

April 15, 2015

First Posted

April 28, 2015

Study Start

April 1, 2015

Primary Completion

January 1, 2025

Study Completion

December 1, 2025

Last Updated

August 7, 2025

Record last verified: 2025-08

Locations

CO(1)CH(1)SG(1)SE(1)CR(1)KA(1)RU(5)IT(14)CN(1)