Protection by Remote Ischemic Preconditioning During Transcatheter Aortic Valve Implantation

November 1, 2016 updated by: Philipp Kahlert, University Hospital, Essen

Protection of Heart, Brain and Kidney by Remote Ischemic Preconditioning in Patients Undergoing Transcatheter Aortic Valve Implantation - a Randomized, Single-blind Study

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

  • 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Essen, Germany, 45122
        • Department of Cardiology, West-German Heart Center Essen, University Duisburg-Essen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: 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.
Procedure: 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.
Placebo Comparator: 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.
Procedure: Placebo
Prior to TAVI-procedure, the blood pressure cuff remains uninflated for 30 min.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Extent of periinterventional myocardial injury as reflected by the geometric mean of the area under the curve (AUC) for troponin I serum concentrations
Time Frame: 72 hours postinterventionally after TAVI
72 hours postinterventionally after TAVI

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Periprocedural myocardial infarction according to current Valve Academic Research Consortium (VARC-2) criteria
Time Frame: 72 hours postinterventionally after TAVI
72 hours postinterventionally after TAVI
Incidence of new wall abnormalities and deterioration of overall left ventricular function as assessed by postinterventional transthoracic echocardiography
Time Frame: Within the first week after TAVI
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
Time Frame: Within the first week after TAVI
Within the first week after TAVI
Prevalence and volume of delayed gadolinium enhancement
Time Frame: Within the first week after TAVI
Cardiac MRI will be performed in selected patients.
Within the first week after TAVI
Maximum elevation of serum creatinine concentration
Time Frame: Until 72 hours after TAVI
Until 72 hours after TAVI
Maximum decrease of estimated glomerular filtration rate
Time Frame: Until 72 hours after TAVI
Until 72 hours after TAVI
Incidence of VARC-2 defined acute kidney injury
Time Frame: Until 72 hours after TAVI and until discharge
Until 72 hours after TAVI and until discharge
Total and median per patient number as well as total and median per patient volume of new foci of restricted diffusion
Time Frame: Within the first week after TAVI
Cerebral MRI will be performed in selected patients.
Within the first week after TAVI
Cardioprotective factor release into circulating blood
Time Frame: Day of intervention
Blood samples will be collected at 4 time points: prior to and after RIPC-maneuver/Placebo, after aortic valve implantation and after access site closure. Time frame: approximately 2,5 hours.
Day of intervention
All cause mortality and major adverse cardiac and cerebrovascular events (MACCE) at 30 days
Time Frame: Within the first 30 days after TAVI
Within the first 30 days after TAVI
All cause mortality and major adverse cardiac and cerebrovascular events (MACCE) at 1 year
Time Frame: Within the first year after TAVI
Within the first year after TAVI
All cause mortality and major adverse cardiac and cerebrovascular events (MACCE) after 3 months
Time Frame: Until 3 months after TAVI
Until 3 months after TAVI
VARC-2 defined combined early TAVI safety endpoint at 30 days
Time Frame: Until 30 days after TAVI
Until 30 days after TAVI

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Essen

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Koblenz University of Applied Science

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2013

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2017

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 1, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 4, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 6, 2014

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 2, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 1, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 135355-BO

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Aortic Valve Stenosis

Clinical Trials on Remote ischemic preconditioning (RIPC)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings