Remote Ischaemic Preconditioning for Heart Surgery (RIPHeart-Study)

Remote Ischaemic Preconditioning for Heart Surgery

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.

Study Overview

• Status: Terminated
• Conditions: Myocardial Injury; Mortality
• Intervention / Treatment: Procedure: Remote Ischemic Preconditioning; Procedure: Control/sham procedure (blood pressure cuff)

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.

• Study Type: Interventional
• Enrollment (Actual): 1400
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany
    • University Hospital Aachen (RWTH)
  • Berlin, Germany
    • University Hospital Charité
  • Bonn, Germany
    • University Hospital Bonn
  • Frankfurt/M, Germany
    • University Hospital Frankfurt/M
  • Goettingen, Germany
    • University Hospital Goettingen
  • Kiel, Germany
    • University Hospital Schleswig-Holstein
  • Luebeck, Germany
    • University Hospital of Schleswig-Holstein
  • Magdeburg, Germany
    • University Hospital Magdeburg
  • Rostock, Germany
    • University Hospital Rostock
  • Wuerzburg, Germany
    • University Hospital Wuerzburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: RIPC	Procedure: Remote Ischemic Preconditioning; RIPC will be induced during anesthesia by four 5-min cycles of upper limb ischemia and 5-min reperfusion using a blood-pressure cuff inflated to a pressure 200 mm Hg, whereas the pressure has to be at least 20 mm Hg greater than the systolic arterial pressure measured via the arterial line.
Sham Comparator: CONTROL	Procedure: Control/sham procedure (blood pressure cuff); Sham placement of the blood pressure cuff around a dummy arm inflated to a pressure of 200 mm Hg with four cycles of 5 min inflation and 5 min deflation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of all-cause mortality, non-fatal myocardial infarction, any new stroke, and/or acute renal failure	Time frame until hospital discharge	In-hospital

Secondary Outcome Measures

Outcome Measure	Time Frame
Occurence of any component of the composite outcome	Postoperative hospital discharge, 3 months, 12 months
length of stay on the intensive care unit	Postoperative during hospital stay
total hospital stay	hospital discharge
new onset of atrial fibrillation	In-hospital
Delirium	Postoperative 24, 48, 72, 96 hrs

Collaborators and Investigators

• Sponsor: University Hospital Schleswig-Holstein
• Collaborators: German Research Foundation; University Hospital Frankfurt
• Investigators: Principal Investigator: Patrick Meybohm, MD, University Hospital Frankfurt/ University Hospital Schleswig-Holstein; Principal Investigator: Berthold Bein, MD, DESA, University Hospital Schleswig-Holstein; Principal Investigator: Jochen Cremer, MD, University Hospital Schleswig-Holstein; Principal Investigator: Kai Zacharowski, MD, PhD, University Hospital Frankfurt am Main

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: February 10, 2010
• First Submitted That Met QC Criteria: February 10, 2010
• First Posted (Estimate): February 11, 2010

Study Record Updates

• Last Update Posted (Estimate): December 3, 2015
• Last Update Submitted That Met QC Criteria: December 1, 2015
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: remote ischaemic preconditioning, cardiac surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Ischemia
• Other Study ID Numbers: ME 3559/1-1