Remote Ischemic Preconditioning for Intracranial Aneurysm Treatment (RIPAT)

June 11, 2014 updated by: Martin Ortler, MD MSc, Medical University Innsbruck

The Role of Remote Ischemic Preconditioning in the Prevention of Ischemic Brain Damage During Intracranial Aneurysm Treatment (RIPAT) - A Prospective Randomized Exploratory Study

The RIPAT study is a prospective, randomized, double-blind study organized by the neurovascular group of the Clinical Department of Neurosurgery of Innsbruck Medical University, Innsbruck, Austria. Patients aged 18+ in whom the treatment of an un-ruptured intracranial aneurysm is indicated are eligible for study participation. Prior to aneurysm treatment, with the patient already under general anesthesia, the blood supply to an arm will be restricted for 3x 5minutes by inflating a standard blood pressure cuff. The study hypothesis is that this "remote ischemic preconditioning" maneuver is able to prevent a stroke during the following treatment of the aneurysm.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Prospective, randomized, double-blind, explorative single center clinical trial in patients subjected to the treatment of an un-ruptured intracranial aneurysm, either by surgical clipping or endovascular coiling. Goal of the study is to determine whether remote ischemic preconditioning (RIPC) prior to aneurysm treatment alters various biomarkers associated with ischemic central neuronal tissue damage. The trial takes place at Innsbruck University Hospital of Innsbruck Medical University, Innsbruck, Austria.

Patients fulfilling inclusion criteria are randomly allocated either to pre-interventional ischemic preconditioning (Group A = intervention group) or sham preconditioning (Group B = control group). RIPC is performed by inflating a blood pressure cuff around one upper extremity three times for five minutes with five minutes interval with the patient under general anesthesia prior to the start of the procedure.

Patients, all staff involved in diagnosis and treatment and all study members are blinded to the patients' group affiliation. The anesthesiologist and two staff members who perform preconditioning are not blinded.

Primary outcome is a difference of ± 2SD in the concentration-time curve of a panel of biochemical parameters indicative of cerebral ischemia (S100B, NSE, GFAP, MMP9, MBP, microparticles) in the first five days after the intervention. Secondary outcome parameters are changes in the post-interventional MRI and neuropsychological and clinical outcome at six and 12 months.

CONSORT and TIDieR guidelines will be followed. The trail will be registered in a public database. The trail protocol will be published in an open-access journal.

Study Type

Interventional

Enrollment (Anticipated)

48

Phase

  • Not Applicable

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

  • Austria
      • Innsbruck, Austria, 6020
        • Recruiting
        • Clinical Department of Neurosurgery, Innsbruck Medical University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Martin Ortler, MD, MSc
        • Sub-Investigator:
          • Claudius Thomé, M.D.
        • Sub-Investigator:
          • Selma Tülü, Cand.med.
        • Sub-Investigator:
          • Miriam Mulino, M.D.
        • Sub-Investigator:
          • Daniel Pinggera, M.D.
        • Sub-Investigator:
          • Claudia Unterhofer, M.D.
        • Sub-Investigator:
          • Erich Schmutzhard, M.D.
        • Sub-Investigator:
          • Bettina Pfausler, M.D.
        • Sub-Investigator:
          • Ronny Beer, M.D.
        • Sub-Investigator:
          • Raimund Helbok, M.D.
        • Sub-Investigator:
          • Peter Lackner, M.D.
        • Sub-Investigator:
          • Thomas Benke, M.D.
        • Sub-Investigator:
          • Thomas Bodner, M.D.
        • Sub-Investigator:
          • Margarethe Delazer, M.D.
        • Sub-Investigator:
          • Raffaella Matteucci-Gothe, Ph.D.
        • Sub-Investigator:
          • Uwe Siewert, Ph.D.
        • Sub-Investigator:
          • Philipp Würtinger, M.D.
        • Sub-Investigator:
          • Andrea Griesmacher, M.D.
        • Sub-Investigator:
          • Markus Luger, M.D.
        • Sub-Investigator:
          • Arnulf Benzer, M.D.
        • Sub-Investigator:
          • Franz Wiedermann, M.D.
        • Sub-Investigator:
          • Astrid Grams, M.D.
        • Sub-Investigator:
          • Elke Gizewski, M.D.

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Informed written consent of patient
  • Age > 18 years
  • Intracranial aneurysm, single or multiple, intervention as indicated by interdisciplinary vascular board (includes previously treated aneurysms)
  • Normal baseline MRI

Exclusion Criteria:

  • Clinical or radiological signs of subarachnoid hemorrhage
  • Planned vessel sacrifice as the primary modality for aneurysm treatment
  • Dissecting or mycotic aneurysm
  • Previous history of stroke or TIA within the last six months
  • Signs or symptoms of upper and lower extremity peripheral vascular illness
  • Drugs and lifestyle factors that interfere with biomarker Determination
  • Inability to complete neuropsychological testing for language reasons
  • Patients unable to have an MRI scan for any reason
  • Previous serious cerebral disease that would preclude completion of the protocol or preclude MRI analysis of small strokes
  • Pregnancy

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Remote ischemic preconditioning
Inflation of a blood pressure cuff around an arm with the patient under general anesthesia prior to start aneurysm treatment
Procedure: Remote ischemic preconditioning
The blood pressure cuff is inflated to 200 mmHg for 3 x 5 minutes with 5 minutes of reperfusion by complete cuff deflation each.
Sham Comparator: Sham preconditioning
Sham inflation of a blood pressure cuff around an arm with the patient under general anesthesia prior to start aneurysm treatment
Procedure: Sham preconditioning
The blood pressure cuff is inflated to 10 mmHg for 3 x 5 minutes with 5 minutes of complete cuff deflation each.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area-under-Curve for biomarkers in the first 5 days after aneurysm treatment(S100B, NSE, GFAP, NSE, MMP9, Microparticles)
Time Frame: on admission, after preconditioning but prior to intervention, at completion of intervention, at hours 3, 6, 12, 24, 48, 72, 96, 120 after completion of intervention
Serum biomarkers reflect brain tissue ischemic damage with various specificity and sensitivity (see Whiteley 2008, Ahmad 2012) Advantages include (1) to be available early, (2) to be continuous variables (low study n), (3) they were able to demonstrate an effect of ischemic preconditioning in other clinical studies (see Koch 2010, Veighei 2012)
on admission, after preconditioning but prior to intervention, at completion of intervention, at hours 3, 6, 12, 24, 48, 72, 96, 120 after completion of intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number (n) of new lesions in postinterventional MRI (DWI and FLAIR)
Time Frame: preinterventional/on day 1 or 2
Outcome Parameter used in other clinical studies focussing on ischemia after neurointerventional procedures (e.g. ENACT study)
preinterventional/on day 1 or 2
Clinical outcome ( National Institutes of Health Stroke Scale, NIHSS and modified Rankin Scale mRS)
Time Frame: at discharge, at 6 and 12 months
Established outcome parameters for cerebrovascular studies. Dichotomized into favourable (NIHSS ≤1, mRS 0-1) and unfavourable
at discharge, at 6 and 12 months
Volume (mm3) of new lesions in postinterventional MRI (DWI and FLAIR)
Time Frame: preinterventional, postinterventional on day 1 or 2
As above for number of lesions
preinterventional, postinterventional on day 1 or 2

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neuropsychological testing VLMTA (Verbaler Lern- und Merkfähigkeitstest), the WMS-R (Zahlenspanne vorwärts und rückwärts), trail making A and B tests, the Regensburger Wortflüssigkeitstest, the TAP Wechsel verbal, the TAP and the HADS-D)
Time Frame: preinterventional, at 6 and 12 months
Standard tests used in patients with cerebrovascular disorders in our departments. Not applicable to non-german-speaking patients.
preinterventional, at 6 and 12 months
Brain volume changes (MRI, voxel -based morphometry)
Time Frame: Preinterventional/at the 12 months FU
Longterm brain volume changes that correlate with NP deficits (Horstmann 2010, Moskowitz 2011, Vuylsteke 2011) will be analyzed using voxel-based morphometry techniques
Preinterventional/at the 12 months FU

Collaborators and Investigators

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

Sponsor

Medical University Innsbruck

Investigators

  • Principal Investigator: Martin Ortler, M.D., MSc., Clinical Department of Neurosurgery, Innsbruck Medical University

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

November 1, 2013

Primary Completion (Anticipated)

November 1, 2015

Study Completion (Anticipated)

November 1, 2016

Study Registration Dates

First Submitted

June 10, 2014

First Submitted That Met QC Criteria

June 11, 2014

First Posted (Estimate)

June 13, 2014

Study Record Updates

Last Update Posted (Estimate)

June 13, 2014

Last Update Submitted That Met QC Criteria

June 11, 2014

Last Verified

June 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20131101-823

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.

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