Protection by Remote Ischemic Preconditioning During Transcatheter Aortic Valve Implantation

NCT02080299 | Unknown Phase 2 DMC

• 1 other identifier: 135355-BO
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Transcatheter aortic valve implantation (TAVI) has rapidly been adopted into clinical practice, but concerns have been raised regarding periprocedural complications like e.g. myocardial injury, stroke or acute kidney injury. Remote ischemic preconditioning (RIPC) with upper limb ischemia/reperfusion provides perioperative myocardial protection in patients undergoing elective coronary artery bypass surgery. The present study assesses protection of heart, brain and kidney by RIPC in patients undergoing TAVI. The study also addresses safety and clinical outcome.

Conditions

Aortic Valve Stenosis

Outcome Measures

Primary Outcomes (1)

• Extent of periinterventional myocardial injury as reflected by the geometric mean of the area under the curve (AUC) for troponin I serum concentrations

  72 hours postinterventionally after TAVI

Secondary Outcomes (13)

• Periprocedural myocardial infarction according to current Valve Academic Research Consortium (VARC-2) criteria

  72 hours postinterventionally after TAVI

• Incidence of new wall abnormalities and deterioration of overall left ventricular function as assessed by postinterventional transthoracic echocardiography

  Within the first week after TAVI

• Incidence of new-onset cardiac arrhythmias including the necessity of defibrillation or transient/permanent pacemaker implantation as assessed by continuous ECG-monitoring

  Within the first week after TAVI

• Prevalence and volume of delayed gadolinium enhancement

  Within the first week after TAVI

• Maximum elevation of serum creatinine concentration

  Until 72 hours after TAVI

Study Arms (2)

Remote ischemic preconditioning (RIPC)

ACTIVE COMPARATOR

RIPC-protocol before TAVI: after induction of conscious sedation/anesthesia, but prior to TAVI procedure, remote ischemic preconditioning (RIPC) protocol is performed, consisting of 3 cycles of 5 minutes left upper arm ischemia by inflation of a blood pressure cuff to 200 mmHg and 5 minutes of reperfusion, followed by a time interval between the end of the last deflation and local groin anaesthesia with subsequent skin puncture of 30 min.

Procedure: Remote ischemic preconditioning (RIPC)

Placebo

PLACEBO COMPARATOR

Placebo protocol before TAVI: After induction of conscious sedation/anesthesia and before TAVI, the cuff is left uninflated for 30 min, followed by a further time interval of 30 min until local groin anaesthesia with subsequent skin puncture.

Procedure: Placebo

Interventions

Remote ischemic preconditioning (RIPC) PROCEDURE

3 circles of 5 min left upper arm ischemia by inflation of a blood pressure cuff to 200 mmHg and 5 min reperfusion, preceding TAVI procedure.

Remote ischemic preconditioning (RIPC)

Placebo PROCEDURE

Prior to TAVI-procedure, the blood pressure cuff remains uninflated for 30 min.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients with severe symptomatic native aortic valve stenosis scheduled for elective TAVI due to a prohibitive or high risk for surgical aortic valve replacement as judged by the institutional heart team based on risk scores and comorbidity assessment
• Written informed consent

You may not qualify if:

• Life expectancy \< 1 year
• Patients who are unlikely to gain improvement in their quality of life by TAVI procedure
• Unfavorable anatomy for TAVI (e.g. inadequate annulus size)
• Left-ventricular thrombus
• Active endocarditis
• Active infection
• Acute ST-segment elevation myocardial infarction
• Hemodynamic instability
• Preoperative troponin I concentration above the upper normal limit of 0.1 ng/ml
• Stroke within the last 6 weeks
• Acute or chronic hemodialysis

Sponsors & Collaborators

• University Hospital, Essen: lead
• Koblenz University of Applied Science: collaborator

Study Sites (1)

Department of Cardiology, West-German Heart Center Essen, University Duisburg-Essen

Essen, 45122, Germany

Location

Related Publications (8)

• Thielmann M, Kottenberg E, Boengler K, Raffelsieper C, Neuhaeuser M, Peters J, Jakob H, Heusch G. Remote ischemic preconditioning reduces myocardial injury after coronary artery bypass surgery with crystalloid cardioplegic arrest. Basic Res Cardiol. 2010 Sep;105(5):657-64. doi: 10.1007/s00395-010-0104-5. Epub 2010 May 21.

  PMID: 20495811 BACKGROUND

• Kottenberg E, Thielmann M, Bergmann L, Heine T, Jakob H, Heusch G, Peters J. Protection by remote ischemic preconditioning during coronary artery bypass graft surgery with isoflurane but not propofol - a clinical trial. Acta Anaesthesiol Scand. 2012 Jan;56(1):30-8. doi: 10.1111/j.1399-6576.2011.02585.x. Epub 2011 Nov 21.

  PMID: 22103808 BACKGROUND

• Heusch G, Musiolik J, Kottenberg E, Peters J, Jakob H, Thielmann M. STAT5 activation and cardioprotection by remote ischemic preconditioning in humans: short communication. Circ Res. 2012 Jan 6;110(1):111-5. doi: 10.1161/CIRCRESAHA.111.259556. Epub 2011 Nov 23.

  PMID: 22116817 BACKGROUND

• Kottenberg E, Musiolik J, Thielmann M, Jakob H, Peters J, Heusch G. Interference of propofol with signal transducer and activator of transcription 5 activation and cardioprotection by remote ischemic preconditioning during coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2014 Jan;147(1):376-82. doi: 10.1016/j.jtcvs.2013.01.005. Epub 2013 Mar 1.

  PMID: 23465551 BACKGROUND

• Thielmann M, Kottenberg E, Kleinbongard P, Wendt D, Gedik N, Pasa S, Price V, Tsagakis K, Neuhauser M, Peters J, Jakob H, Heusch G. Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial. Lancet. 2013 Aug 17;382(9892):597-604. doi: 10.1016/S0140-6736(13)61450-6.

  PMID: 23953384 BACKGROUND

• Kleinbongard P, Thielmann M, Jakob H, Peters J, Heusch G, Kottenberg E. Nitroglycerin does not interfere with protection by remote ischemic preconditioning in patients with surgical coronary revascularization under isoflurane anesthesia. Cardiovasc Drugs Ther. 2013 Aug;27(4):359-61. doi: 10.1007/s10557-013-6451-3. No abstract available.

  PMID: 23440355 BACKGROUND

• Kahlert P, Knipp SC, Schlamann M, Thielmann M, Al-Rashid F, Weber M, Johansson U, Wendt D, Jakob HG, Forsting M, Sack S, Erbel R, Eggebrecht H. Silent and apparent cerebral ischemia after percutaneous transfemoral aortic valve implantation: a diffusion-weighted magnetic resonance imaging study. Circulation. 2010 Feb 23;121(7):870-8. doi: 10.1161/CIRCULATIONAHA.109.855866.

  PMID: 20177005 BACKGROUND

• Kahlert P, Hildebrandt HA, Patsalis PC, Al-Rashid F, Janosi RA, Nensa F, Schlosser TW, Schlamann M, Wendt D, Thielmann M, Kottenberg E, Frey U, Neuhauser M, Forsting M, Jakob HG, Rassaf T, Peters J, Heusch G, Kleinbongard P. No protection of heart, kidneys and brain by remote ischemic preconditioning before transfemoral transcatheter aortic valve implantation: Interim-analysis of a randomized single-blinded, placebo-controlled, single-center trial. Int J Cardiol. 2017 Mar 15;231:248-254. doi: 10.1016/j.ijcard.2016.12.005. Epub 2016 Dec 6.

  PMID: 27940009 DERIVED

MeSH Terms

Conditions

Aortic Valve Stenosis

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Study Officials

• Philipp Kahlert, MD

  Department of Cardiology, West-German Heart Center Essen, University Duisburg-Essen

  PRINCIPAL INVESTIGATOR

• Matthias Thielmann, MD

  Department of Thoracic and Cardiovascular Surgery, West-German Heart Center Essen, University Duisburg-Essen

  PRINCIPAL INVESTIGATOR

• Petra Kleinbongard, PhD

  Institute of Pathophysiology, University Duisburg-Essen

  PRINCIPAL INVESTIGATOR

• Eva Kottenberg, MD

  Clinic for Anesthesiology and Intensive Care Medicine, University Duisburg-Essen

  PRINCIPAL INVESTIGATOR

• Jürgen Peters, MD

  Clinic for Anesthesiology and Intensive Care Medicine, University Duisburg-Essen

  PRINCIPAL INVESTIGATOR

• Heinz Jakob, MD

  Department of Thoracic and Cardiovascular Surgery, West-German Heart Center Essen, University Duisburg-Essen

  PRINCIPAL INVESTIGATOR

• Raimund Erbel, MD

  Department of Cardiology, West-German Heart Center Essen, University Duisburg-Essen

  PRINCIPAL INVESTIGATOR

• Gerd Heusch, MD, PhD

  Institute of Pathophysiology, University Duisburg-Essen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: March 1, 2014
• First Posted: March 6, 2014
• Study Start: September 1, 2013
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: November 2, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)