Remote Ischaemic Preconditioning for Heart Surgery (RIPHeart-Study)

• ClinicalTrials.gov Identifier: NCT01067703
• Recruitment Status: Terminated
• First Posted: February 11, 2010
• Last Update Posted: December 3, 2015
• Sponsor: University Hospital Schleswig-Holstein
• Collaborators: German Research Foundation; University Hospital, Frankfurt
• Information provided by (Responsible Party): Patrick Meybohm, University Hospital Schleswig-Holstein

Tracking Information

• First Submitted Date: February 10, 2010
• First Posted Date: February 11, 2010
• Last Update Posted Date: December 3, 2015
• Study Start Date: December 2010
• Actual Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 28, 2013)

Composite of all-cause mortality, non-fatal myocardial infarction, any new stroke, and/or acute renal failure [ Time Frame: In-hospital ]

Time frame until hospital discharge

• Original Primary Outcome Measures (submitted: February 10, 2010): Composite of all-cause mortality, non-fatal myocardial infarction, any new stroke, and/or acute renal failure [ Time Frame: Postoperative 30 days ]

Current Secondary Outcome Measures (submitted: November 30, 2011)

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

Original Secondary Outcome Measures (submitted: February 10, 2010)

• Occurence of any componet of the composite [ Time Frame: Postoperative hospital discharge, 3 months, 12 months ]
• length of stay on the intensive care unit [ Time Frame: Postoperative during hospital stay ]
• total hospital stay [ Time Frame: hospital discharge ]
• new onset of atrial fibrillation [ Time Frame: Postoperative 30 days ]
• Delirium [ Time Frame: Postoperative 24, 48, 72, 96 hrs ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Remote Ischaemic Preconditioning for Heart Surgery (RIPHeart-Study)
• Official Title: Remote Ischaemic Preconditioning for Heart Surgery
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention

Condition

• Myocardial Injury
• Mortality

Intervention

• 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.
• 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.

Study Arms

• Active Comparator: RIPC
  Intervention: Procedure: Remote Ischemic Preconditioning
• Sham Comparator: CONTROL
  Intervention: Procedure: Control/sham procedure (blood pressure cuff)

Publications *

• Meybohm P, Bein B, Brosteanu O, Cremer J, Gruenewald M, Stoppe C, Coburn M, Schaelte G, Böning 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, Schön 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.
• Meybohm P, Zacharowski K, Cremer J, Roesner J, Kletzin F, Schaelte G, Felzen M, Strouhal U, Reyher C, Heringlake M, Schön 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). pii: e008077. doi: 10.1161/JAHA.117.008077.
• 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: September 1, 2014): 1400
• Original Estimated Enrollment (submitted: February 10, 2010): 2070
• Actual Study Completion Date: May 2015
• Actual Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT01067703
• Other Study ID Numbers: ME 3559/1-1
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Patrick Meybohm, University Hospital Schleswig-Holstein
• Study 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

• PRS Account: University Hospital Schleswig-Holstein
• Verification Date: September 2014