TransCranial Doppler for REDUCtion of Silent strokE During MitraClip Implantation (TCD-REDUCE)

The primary goal of the TCD-REDUCE study is to demonstrate the effectiveness of continuous transcranial Doppler sonography ("sonolysis") on the reduction of the ischemic stroke volume during MitraClip implantation.

Study Overview

• Status: Recruiting
• Conditions: Mitral Valve Insufficiency
• Intervention / Treatment: Procedure: Sonolysis

Detailed Description

Cardiac procedures are associated with new cerebral ischemic lesions detected on diffusion-weighted MRI (Bendszus et al., 2006).

A previous study suggests that sonolysis (continuous transcranial Doppler sonography using a 2-MHz diagnostic probe) can reduce the risk of new cerebral ischemic lesions during carotid endarterectomy and carotid angioplasty / stenting (Skoloudik et al., 2015).

Currently, it is unknown whether sonolysis can also reduce the risk of new cerebral ischemic lesions during MitraClip implantation - a percutaneous treatment option in patients with moderate / severe mitral regurgitation.

In this study, patients will receive cerebral MRI and clinical neurological / neuropsychological examination before and after MitraClip implantation. During MitraClip implantation, all patients will receive continuous transcranial Doppler sonography using a 2-MHz diagnostic probe with maximal diagnostic energy administered through either the left or the right transtemporal window (computer-generated 1:1 randomization).

The primary endpoint is the median ischemic lesion volume detected on diffusion-weighted MRI after MitraClip implantation in the sonolysis group and in the control group.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tim Bastian Braemswig, MD; Phone Number: +49 30 450560624; Email: tim-bastian.braemswig@charite.de

Study Locations

• Germany
  • Berlin, Germany, 12200
    • Recruiting
    • Charitè-Campus Benjamin Franklin
    • Contact: Tim Bastian Braemswig, MD
    • Principal Investigator: Christian H Nolte, Prof.
    • Sub-Investigator: Tim Bastian Braemswig, MD
    • Sub-Investigator: Markus Reinthaler, MD
    • Sub-Investigator: Alexander Lauten, Prof.
    • Sub-Investigator: Jochen B Fiebach, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patients with mitral regurgitation that are assigned to the MitraClip implantation by an interdisciplinary heart team according to current guidelines.

Exclusion Criteria:

• contraindication to MRI examination (e.g. pace-maker, implanted metal material, claustrophobia)
• pregnancy
• unable to consent
• no transtemporal window

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sonolysis group; Cerebral hemisphere with sonolysis during MitraClip implantation.	Procedure: Sonolysis; Continuous transcranial Doppler sonography (TCD) using a 2-MHz diagnostic probe with maximal diagnostic energy
No Intervention: Control group; Cerebral hemisphere without sonolysis during MitraClip implantation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
stroke volume	median volume (in ml) of new ischemic lesions detected on diffusion-weighted MRI after MitraClip implantation in the sonolysis and in the control group	0-5 days after the MitraClip Implantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
diffusion-weighted MRI lesions	new ischemic lesions (occurrence, number and location) detected on diffusion-weighted MRI after MitraClip implantation	0-5 days after the MitraClip Implantation
intracerebral hemorrhage (ICH) and / or subarachnoid hemorrhage (SAH)	new ICH and / or SAH detected on T2*-weighted MRI after MitraClip implantation	0-5 days after the MitraClip Implantation
cerebral microbleeds (CMB)	new cerebral microbleeds detected on T2*-weighted MRI after MitraClip implantation (occurrence, number and location)	0-5 days after the MitraClip Implantation
clinically overt stroke	new clinically overt stroke (ischemic or hemorrhagic) or transient ischemic attack (TIA) after MitraClip implantation	(1) 0-5 days after the MitraClip Implantation and (2) 3 months after MitraClip implantation
functional outcome	functional outcome will be evaluated using the modified Rankin scale (mRS). The mRS ranges from 0 to 6 with 0 indicating no functional deficit (best score) and 6 indicating deaths (worst score).	(1) 0-5 days after the MitraClip Implantation and (2) 3 months after MitraClip implantation
cognitive outcome during hospital stay	cognitive outcome will be evaluated using the Montreal Cognitive Assessment (MoCA)	0-5 days after the MitraClip Implantation
cognitive outcome at follow-up	cognitive outcome will be evaluated using the Telephone Interview for Cognitive Status (TICS)	3 months after MitraClip implantation
delirium	delirium will be evaluated using the 3-Minute Diagnostic Interview for Confusion Assessment Method (3D-CAM)	0-5 days after the MitraClip Implantation
length of hospital stay (duration of hospitalization for the MitraClip implantation)	days of hospital stay from admission to hospital to discharge from hospital including direction of discharge (home, another hospital)	length of hospital stay (up to 3 months after MitraClip implantation)
mortality	mortality	up to 3 months after MitraClip implantation

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: Berlin Institute of Health
• Investigators: Principal Investigator: Christian H Nolte, Prof., Charite University, Berlin, Germany

Publications and helpful links

General Publications

• Skoloudik D, Kuliha M, Hrbac T, Jonszta T, Herzig R; SONOBUSTER Trial Group. Sonolysis in Prevention of Brain Infarction During Carotid Endarterectomy and Stenting (SONOBUSTER): a randomized, controlled trial. Eur Heart J. 2016 Oct 21;37(40):3096-3102. doi: 10.1093/eurheartj/ehv492. Epub 2015 Sep 28.

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2020
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: April 30, 2020
• First Submitted That Met QC Criteria: May 11, 2020
• First Posted (Actual): May 12, 2020

Study Record Updates

• Last Update Posted (Actual): September 6, 2023
• Last Update Submitted That Met QC Criteria: September 5, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Stroke; MitraClip; Sonolysis
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Mitral Valve Insufficiency
• Other Study ID Numbers: EA4/193/19

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No