Remote Ischemic Preconditioning in Patients Undergoing Isolated Aortic Valve Replacement Surgery

Remote Ischemic Preconditioning in Patients Undergoing Isolated Aortic Valve Replacement Surgery With a Biological Prosthesis: A Single Center Randomized Prospective Study

The goal is to investigate the efficacy, safety and possible neuro- and cardioprotective effects of remote ischemic preconditioning (RIPC) in adult cardiac patients undergoing isolated aortic valve replacement surgery with a biological prosthesis. Neuropsychological evaluation preoperatively and at 30d after surgery will establish if there are any differences in neuropsychological performance between groups. A large array of biochemical markers will be analyzed from plasma samples taken at different time points. Additionally skin biopsies from the lower limb will be taken before and after performing RIPC on said limb. During the venous cannulation phase a atrial biopsy will be taken. The biochemical markers from plasma and tissue samples will be used to asses brain tissue damage, inflammation and cardiac tissue damage between groups.

This will be a single center prospective randomized study with two groups. A intervention group (RIPC) and a control group. Study size is: 40 patients in total, 20 patients per group.

Study Overview

• Status: Terminated
• Conditions: Myocardial Ischemia; Aortic Valve Disease
• Intervention / Treatment: Procedure: Remote ischemic preconditioning

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Finland
  • Oulu, Finland, 900220
    • Oulu University Hospital, Department of Cardiothoracic surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 58 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Non-emergency aortic valve replacement with a biological prosthesis with perfusion and cardiac arrest

Exclusion Criteria:

• Recent myocardial infarction
• Carotid stenosis requiring intervention
• Any other concomitant surgical procedure
• Increased troponin baseline before surgery
• Critical ischemia of lower limbs
• Peripheral arterial disease (ASO, media sclerosis)
• Morbid obesity (Incompatible cuff-to-thigh diameter)
• Severe heart insufficiency
• Moderate to severe venous insufficiency lower limbs
• Recent acute stroke <90d
• Difference in cardioplegic protocol
• Diseased aorta in epiaortic ultrasound

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remote ischemic preconditioning; Patient will undergo normal isolated aortic valve replacement surgery with a biological prosthesis and a preoperative lower leg remote ischemic preconditioning(RIPC) phase.	Procedure: Remote ischemic preconditioning; A blood pressure cuff is placed around the right leg on the level of the thigh. Randomization is performed after this, using sealed envelopes with covariate balancing for age and sex. Regardless of the outcome of the randomization the cuff is left in place so as not to give any indication of which group the patient belongs to. If the patient is randomized into the remote ischemic preconditioning group (RIPC) then four (4) cycles of five (5) minute inflation are given after induction. Each cycle is followed by a five (5) minute interval of reperfusion. Cuff pressure should be 200mgHg at least (RRsyt + 100mmgHg) during the inflation periods.
No Intervention: Control group; Patient will undergo normal isolated aortic valve replacement surgery with a biological prosthesis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropsychological assesment	Investigators will use a neuropsychological test battery to test our subject pre- and post-operatively. A qualified psychologist will administer the test battery. The test battery will be relatively simple but still have several different tests. These tests will include but are not limited to: - Trail Making test A & B (TMT)	1 month postoperatively
Neuropsychological assesment	Digit Span test	1 month postoperatively
Neuropsychological assesment	Rey Auditory Verbal Learning Test (RAVLT)	1 month postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammation markers analysed from plasma and tissue samples	A bioplex/multiplex assay of systemic inflammatory response markers and other cytokines including but not limited to: Tumor Necrosis Factor-a, Interleukin-1b, -2, -4, -5, -6. C-Reactive Protein, Hypoxia inducible Factor -1.	A day before surgery, during surgery, 24hour and 48hour postoperatively
Tissue specific markers analysed from plasma	A bioplex/multiplex assay of neuronal and cardiac tissue specific biomarkers including but not limited to: S-100b, Glial Fibrillary acidic protein, Neuron Specific enolase, Troponin-I, Brain Natriuretic Peptide, Creatinine Kinase - MB	A day before surgery, during surgery, 24hour and 48hour postoperatively

Collaborators and Investigators

• Sponsor: Oulu University Hospital
• Investigators: Study Director: Fredrik Yannopoulos, MD Ph.D, Oulu University Hospital; Study Chair: Vesa Anttila, MD Ph.D., Oulu University Hospital; Principal Investigator: Tuomas Ahvenvaara, MD, Oulu University Hospital; Principal Investigator: Tuomas Mäkelä, MD.Ph.D., Oulu University Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: February 18, 2016
• First Submitted That Met QC Criteria: February 26, 2016
• First Posted (Estimate): February 29, 2016

Study Record Updates

• Last Update Posted (Actual): April 4, 2018
• Last Update Submitted That Met QC Criteria: April 3, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Neuroprotection; Remote ischemic preconditioning
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Heart Valve Diseases; Myocardial Ischemia; Ischemia; Aortic Valve Disease
• Other Study ID Numbers: RIPC00AVR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Study Data/Documents

1. Study Protocol
   Information comments: English protocol description file
2. Informed Consent Form
   Information comments: Finnish language consent form
3. Patient information in Finnish
   Information comments: Patient information in Finnish