Clinical trial NCT01067703: Remote Ischaemic Preconditioning for Heart Surgery (RIPHeart-Study)
Official title: Remote Ischaemic Preconditioning for Heart Surgery
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Myocardial Injury
Mortality
Keywords: remote ischaemic preconditioning, cardiac surgery
Lead sponsor: University Hospital Schleswig-Holstein
Sponsor class: OTHER
Collaborators: name: German Research Foundation
name: Goethe University
First posted: 2010-02-11
Enrollment: 1400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate the effects of Remote Ischaemic Preconditioning on perioperative ischaemic injury in patients undergoing cardiac surgery compared to control intervention.

Detailed description: Cardiac surgery with cardiopulmonary bypass is associated with a predictable incidence of myocardial, neurological and renal dysfunction. This significant morbidity and mortality is at least partly due to perioperative ischaemia. Remote ischaemic preconditioning (RIPC) is a novel, simple, non-invasive and inexpensive intervention by which ischaemia of non-vital tissue (skeletal muscles) protects remote organs (heart, brain and kidney) from a subsequent sustained episode of ischaemia. The investigators perform a multicenter randomized controlled study to evaluate that RIPC reduces teh severity of perioperative ischaemic injury in patients undergoing cardiac surgery, and results in about 1/3 risk reduction in the occurence of major adverse events.

Eligibility criteria: Inclusion Criteria:

* patients undergoing heart surgery on cardiopulmonary bypass

Exclusion Criteria:

* age \< 18
* Emergency cases
* left ventricular ejection fraction less than 30%
* current atrial fibrillation
* Inability to give informed consent
* preoperative use of inotropics or mechanical assist device
* severe liver, renal and pulmonary disease
* recent myocardial infarction (within 7 days)
* recent systemic infection or sepsis (within 7 days)
* severe stroke (within 2 months)
* peripheral vascular disease affecting upper limbs
* previous serious psychiatric disorders (e.g. schizophrenia, dementia)
* concomitant carotid endarterectomy
* rare surgeries: cardiac transplantation, correction of complicated congenital anomalies, pulmonary thromboembolectomy, off-pump surgery, minimal-invasive operation without sternotomy

Primary outcomes:
measure: Composite of all-cause mortality, non-fatal myocardial infarction, any new stroke, and/or acute renal failure
timeFrame: In-hospital
Secondary outcomes:
measure: Occurence of any component of the composite outcome
timeFrame: Postoperative hospital discharge, 3 months, 12 months
measure: length of stay on the intensive care unit
timeFrame: Postoperative during hospital stay
measure: total hospital stay
timeFrame: hospital discharge
measure: new onset of atrial fibrillation
timeFrame: In-hospital
measure: Delirium
timeFrame: Postoperative 24, 48, 72, 96 hrs
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: University Hospital Aachen (RWTH)
city: Berlin
country: Germany
facility: University Hospital Charite
city: Bonn
country: Germany
facility: University Hospital Bonn
city: Frankfurt/M
country: Germany
facility: University Hospital Frankfurt/M
city: Goettingen
country: Germany
facility: University Hospital Goettingen
city: Kiel
country: Germany
facility: University Hospital Schleswig-Holstein
city: Luebeck
country: Germany
facility: University Hospital of Schleswig-Holstein
city: Magdeburg
country: Germany
facility: University Hospital Magdeburg
city: Rostock
country: Germany
facility: University Hospital Rostock
city: Wuerzburg
country: Germany
facility: University Hospital Wuerzburg
Study officials:
affiliation: University Hospital Frankfurt/ University Hospital Schleswig-Holstein
name: Patrick Meybohm, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Schleswig-Holstein
name: Berthold Bein, MD, DESA
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Schleswig-Holstein
name: Jochen Cremer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Frankfurt am Main
name: Kai Zacharowski, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Meybohm P, Bein B, Brosteanu O, Cremer J, Gruenewald M, Stoppe C, Coburn M, Schaelte G, Boning A, Niemann B, Roesner J, Kletzin F, Strouhal U, Reyher C, Laufenberg-Feldmann R, Ferner M, Brandes IF, Bauer M, Stehr SN, Kortgen A, Wittmann M, Baumgarten G, Meyer-Treschan T, Kienbaum P, Heringlake M, Schon J, Sander M, Treskatsch S, Smul T, Wolwender E, Schilling T, Fuernau G, Hasenclever D, Zacharowski K; RIPHeart Study Collaborators. A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery. N Engl J Med. 2015 Oct 8;373(15):1397-407. doi: 10.1056/NEJMoa1413579. Epub 2015 Oct 5.
citation: Meybohm P, Zacharowski K, Cremer J, Roesner J, Kletzin F, Schaelte G, Felzen M, Strouhal U, Reyher C, Heringlake M, Schon J, Brandes I, Bauer M, Knuefermann P, Wittmann M, Hachenberg T, Schilling T, Smul T, Maisch S, Sander M, Moormann T, Boening A, Weigand MA, Laufenberg R, Werner C, Winterhalter M, Treschan T, Stehr SN, Reinhart K, Hasenclever D, Brosteanu O, Bein B; RIP Heart-Study Investigator Group. Remote ischaemic preconditioning for heart surgery. The study design for a multi-center randomized double-blinded controlled clinical trial--the RIPHeart-Study. Eur Heart J. 2012 Jun;33(12):1423-6.
citation: Westphal S, Stoppe C, Gruenewald M, Bein B, Renner J, Cremer J, Coburn M, Schaelte G, Boening A, Niemann B, Kletzin F, Roesner J, Strouhal U, Reyher C, Laufenberg-Feldmann R, Ferner M, Brandes IF, Bauer M, Kortgen A, Stehr SN, Wittmann M, Baumgarten G, Struck R, Meyer-Treschan T, Kienbaum P, Heringlake M, Schoen J, Sander M, Treskatsch S, Smul T, Wolwender E, Schilling T, Degenhardt F, Franke A, Mucha S, Tittmann L, Kohlhaas M, Fuernau G, Brosteanu O, Hasenclever D, Zacharowski K, Meybohm P; RIPHeart-Study Collaborators. Genome-wide association study of myocardial infarction, atrial fibrillation, acute stroke, acute kidney injury and delirium after cardiac surgery - a sub-analysis of the RIPHeart-Study. BMC Cardiovasc Disord. 2019 Jan 24;19(1):26. doi: 10.1186/s12872-019-1002-x.
citation: Meybohm P, Kohlhaas M, Stoppe C, Gruenewald M, Renner J, Bein B, Albrecht M, Cremer J, Coburn M, Schaelte G, Boening A, Niemann B, Sander M, Roesner J, Kletzin F, Mutlak H, Westphal S, Laufenberg-Feldmann R, Ferner M, Brandes IF, Bauer M, Stehr SN, Kortgen A, Wittmann M, Baumgarten G, Meyer-Treschan T, Kienbaum P, Heringlake M, Schoen J, Treskatsch S, Smul T, Wolwender E, Schilling T, Fuernau G, Bogatsch H, Brosteanu O, Hasenclever D, Zacharowski K; RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study Collaborators. RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study: Myocardial Dysfunction, Postoperative Neurocognitive Dysfunction, and 1 Year Follow-Up. J Am Heart Assoc. 2018 Mar 26;7(7):e008077. doi: 10.1161/JAHA.117.008077.
citation: Candilio L, Malik A, Ariti C, Barnard M, Di Salvo C, Lawrence D, Hayward M, Yap J, Roberts N, Sheikh A, Kolvekar S, Hausenloy DJ, Yellon DM. Effect of remote ischaemic preconditioning on clinical outcomes in patients undergoing cardiac bypass surgery: a randomised controlled clinical trial. Heart. 2015 Feb;101(3):185-92. doi: 10.1136/heartjnl-2014-306178. Epub 2014 Sep 24.