Protection by Remote Ischemic Preconditioning During Transcatheter Aortic Valve Implantation

NCT ID: NCT02080299

Last Updated: 2016-11-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-09-30

Study Completion Date

2017-08-31

Brief Summary

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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.

Detailed Description

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* On the assumption of our recent data (Thielmann et al, Lancet 2013, 382(9892):597-604), we performed a power analysis, revealing an estimated enrollment of 189 patients per group. But since no true data exist regarding RIPC and TAVI, interim analysis will be performed after 50 patients per group.
* After induction of conscious sedation or general anaesthesia, RIPC is accomplished by 3 cycles of 5 min inflation/5 min deflation of a blood pressure cuff around the left arm to 200 mm Hg. In the placebo group, the blood pressure cuff remains uninflated for 30 min.
* Blind: study coordinators, outcome assessors, operators and treating physicians except for the attending anaesthetist.
* Drugs used for conscious sedation: midazolam, remifentanil.
* Drugs used for general anaesthesia: sufentanil, etomidate, rocuronium, isoflurane.
* TAVI is performed by standard techniques using the balloon-expandable Sapien XT (Edwards Lifesciences Inc., Irvine, California, USA) and the next-generation Sapien 3 stent-valve bioprosthesis which replaces the Sapien XT prosthesis, when CE-approved.
* Arterial blood samples are obtained prior to and after RIPC-maneuver/Placebo, after aortic valve implantation and after access site closure, for biochemical analyses focussing on ligands that have been previously implicated in conditioning protocols at various organs. A bioassay system, consisting of a Langendorff-perfused isolated heart with ischemia and reperfusion will be used. This bioassay system will be exposed to the obtained arterial plasma of the patients.
* Venous blood samples are drawn before TAVI and at 1, 6, 12, 24, 48 and 72 hours after the procedure.
* Cardiac and cerebral MRI is performed in selected patients at baseline and within the first week after TAVI.
* On-site follow-up at 3±3 months, 12±3 months and yearly thereafter.

Conditions

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Aortic Valve Stenosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Investigators

Study Groups

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Remote ischemic preconditioning (RIPC)

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.

Group Type ACTIVE_COMPARATOR

Remote ischemic preconditioning (RIPC)

Intervention Type 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.

Placebo

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type PROCEDURE

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

Interventions

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Remote ischemic preconditioning (RIPC)

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.

Intervention Type PROCEDURE

Placebo

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

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Koblenz University of Applied Science

OTHER

Sponsor Role collaborator

University Hospital, Essen

OTHER

Sponsor Role lead

Responsible Party

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Philipp Kahlert

MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Philipp Kahlert, MD

Role: PRINCIPAL_INVESTIGATOR

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

Matthias Thielmann, MD

Role: PRINCIPAL_INVESTIGATOR

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

Petra Kleinbongard, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Pathophysiology, University Duisburg-Essen

Eva Kottenberg, MD

Role: PRINCIPAL_INVESTIGATOR

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

Jürgen Peters, MD

Role: PRINCIPAL_INVESTIGATOR

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

Heinz Jakob, MD

Role: PRINCIPAL_INVESTIGATOR

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

Raimund Erbel, MD

Role: PRINCIPAL_INVESTIGATOR

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

Gerd Heusch, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Pathophysiology, University Duisburg-Essen

Locations

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

Essen, , Germany

Site Status

Countries

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Germany

References

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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.

Reference Type BACKGROUND
PMID: 20495811 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22103808 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22116817 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23465551 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23953384 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23440355 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20177005 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27940009 (View on PubMed)

Other Identifiers

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135355-BO

Identifier Type: -

Identifier Source: org_study_id