Remote Ischemic Conditioning With Local Ischemic Postconditioning in High-Risk ST-elevation Myocardial Infarction (RIP-HIGH)

Randomized Comparison of Combined Remote Ischemic Conditioning and Local Postconditioning Compared to Standard Treatment in High-risk ST-elevation Myocardial Infarction Patients

The RIP-HIGH trial is a two-arm randomized controlled trial aiming to compare the impact of combined remote ischemic conditioning (RIP) and local ischemic postconditioning (PostC) vs. standard of care on clinical outcome in high-risk ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention.

Study Overview

• Status: Recruiting
• Conditions: ST Elevation Myocardial Infarction
• Intervention / Treatment: Procedure: RIC + PostC + Standard PCI; Procedure: Standard PCI

Detailed Description

Coronary reperfusion by percutaneous coronary intervention is mandatory to salvage ischemic myocardium and to reduce definite infarct size. However, reperfusion itself also causes irreversible myocardial damage - a phenomenon described as reperfusion injury. Reduction of ischemic and reperfusion injury by ischemic conditioning has been identified as a potential target to reduce myocardial damage.

Remote ischemic conditioning and local ischemic postconditioning might be in particular of clinical benefit in higher risk STEMI patients with Killip class ≥2, where mortality rates are high.

The Remote Ischemic Conditioning with Local Ischemic Postconditioning in High-Risk ST-elevation myocardial infarction patients (RIP-HIGH) trial is a two-arm randomized controlled trial aiming to compare the impact of combined remote ischemic conditioning and local ischemic postconditioning vs. standard of care on clinical outcome in high-risk ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention.

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Holger Thiele, Prof. Dr.; Phone Number: +49 341 865 1428; Email: holger.thiele@medizin.uni-leipzig.de
• Study Contact Backup: Name: Hans-Josef Feistritzer, Dr. med.; Phone Number: +49 341 865 1428; Email: hans-josef.feistritzer@medizin.uni-leipzig.de

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Recruiting
    • Medizinische Universität Innsbruck
    • Contact: Sebastian Reinstadler, MD
• Germany
  • Bremen, Germany
    • Recruiting
    • Klinikum Links der Weser
    • Contact: Harm Wienbergen, Prof.
    • Contact: Andreas Fach, Dr.
  • Dresden, Germany, 01307
    • Recruiting
    • Herzzentrum Dresden
    • Contact: Axel HP Linke, Prof. Dr. med
    • Contact: Felix Woitek, Dr. med.
  • Düsseldorf, Germany, 40225
    • Recruiting
    • Universitätsklinikum Düsseldorf
    • Contact: Malte Kelm, Prof. Dr. med.
    • Contact: Ralf Erkens, Dr. med.
  • Essen, Germany
    • Recruiting
    • University Hospital Essen
    • Contact: Tienush Rassaf, Prof.
    • Contact: Amir Abbas Mahabadi, Prof.
  • Hamburg, Germany, 20246
    • Recruiting
    • University Clinic Hamburg-Eppendorf
    • Contact: Peter Clemmensen, Prof.
  • Leipzig, Germany, 04289
    • Recruiting
    • Heart Center Leipzig at University of Leipzig, Department of Internal Medicine/Cardiology
    • Contact: Holger Thiele, Prof. Dr.; Phone Number: +49 341 865 1428; Email: holger.thiele@medizin.uni-leipzig.de
    • Contact: Hans-Josef Feistritzer, Dr. med.; Phone Number: +49 341 865 1428; Email: hans-josef.feistritzer@medizin.uni-leipzig.de
  • Ludwigshafen, Germany, 67063
    • Recruiting
    • Klinikum Ludwigshafen
    • Contact: Uwe Zeymer, Prof.
  • Lübeck, Germany, 23538
    • Recruiting
    • University Heart Center Lübeck - University of Schleswig-Holstein
    • Contact: Ingo Eitel, Prof.
  • Rostock, Germany
    • Recruiting
    • Universitätsmedizin Rostock
    • Contact: Alper Öner, Prof.
    • Contact: Hüseyin Ince, Prof.
  • Tübingen, Germany, 72076
    • Recruiting
    • University Hospital Tübingen
    • Contact: Tobias Geisler, Prof. Dr. med.
    • Contact: Michal Droppa, PD Dr. med.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Acute chest pain lasting <12 h
• ST-elevation at the J-point in two contiguous leads of ≥2 mm in men ≥40 years, ≥2.5 mm in men <40 years and ≥1.5 mm in women (regardless of age) in V2-V3 and/or ≥1 mm in all other leads (52).
• New or presumed new left bundle branch block or right bundle branch block.
• Killip class ≥II on hospital admission or requirement of diuretics because of clinical congestion.
• Written informed consent.

Exclusion Criteria:

• Killip class I on hospital admission.
• Prior fibrinolysis.
• Conditions precluding use of RIC (i.e. paresis of the upper limb, presence of an arteriovenous shunt).
• Pregnancy.
• Age <18 years.
• Severe co-morbidity with a life expectancy <6 months.
• Participation in another trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard treatment	Procedure: Standard PCI; Standard PCI
Experimental: RIC + PostC in addition to standard treatment; RIC by arm ischemia initiated on hospital admission plus local PostC by re-inflating the angioplasty balloon after re-opening the infarct-related artery in addition to standard treatment.	Procedure: RIC + PostC + Standard PCI; RIC by arm ischemia initiated on hospital admission plus local PostC by re-inflating the angioplasty balloon after re-opening the infarct-related artery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite of all-cause mortality or hospitalization for heart failure (HF) within 12 months after randomization.	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
All-cause mortality at 12 months	12 months
Hospitalization for heart failure at 12 months	12 months
Composite of all-cause mortality, HF hospitalization and survived out-of-hospital cardiac arrest at 12 months	12 months
Cardiovascular mortality at 12 months.	12 months
Enzymatic infarct size defined as high-sensitivity cardiac troponin T (hs-TnT) levels 72 h after randomization	day 3
Change in N-terminal pro B-type natriuretic peptide (NT-proBNP) levels during admission and 72 h after randomization	day 0, day 3
Thrombolysis in myocardial infarction (TIMI)-flow grade of the culprit vessel post PCI	day 0
Proportion of patients showing complete (≥70%) resolution of ST-segment elevation 60 minutes after reperfusion	day 0
CMR-derived infarct size.	day 2-5
CMR-derived myocardial salvage index	day 2-5
Extent of CMR-derived late microvascular obstruction on day 2-5 after randomization	day 2-5
all-cause mortality, HF hospitalization and survived out-of-hospital cardiac arrest assessed at 5 years via telephone contact.	5 years

Collaborators and Investigators

• Sponsor: Helios Health Institute GmbH
• Collaborators: Heart Center Leipzig - University Hospital
• Investigators: Study Chair: Holger Thiele, Prof. Dr., Heart Center Leipzig at University of Leipzig, Department of Internal Medicine/Cardiology

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2021
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: March 31, 2021
• First Submitted That Met QC Criteria: April 12, 2021
• First Posted (Actual): April 14, 2021

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: percutaneous coronary intervention; remote ischemic conditioning; local ischemic postconditioning
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Ischemia
• Other Study ID Numbers: 2021-0089

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No