Clinical trial NCT06603454: Preoperative Chest CT-imaging in Surgical Aortic Valve Replacement with or Without CABG
Official title: Preoperative Chest CT-imaging in Surgical Aortic Valve Replacement with or Without CABG: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Aortic Valve Stenosis
Lead sponsor: St. Antonius Hospital
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2024-09-19
Enrollment: 380
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Rationale When determining the strategy for aortic valve replacement, echocardiography is still considered the golden standard (1). While pre-procedural MSCT is standard of care in TAVR patients, this is not yet part of routine clinical practice in SAVR patients. The researchers hypothesise that when atherosclerosis of the ascending aorta is identified preoperatively on contrast-enhanced multi-slice computed tomography (MSCT), the subclinical perioperative stroke rate (as detected on diffusion-weighted magnetic resonance imaging (DW-MRI)) can be reduced by modification of the operative strategy if necessary.

Detailed description: When determining the strategy for aortic valve replacement, echocardiography is still considered the golden standard (1). While pre-procedural MSCT is standard of care in TAVR patients, this is not yet part of routine clinical practice in SAVR patients. The investigators hypothesise that when atherosclerosis of the ascending aorta is identified preoperatively on contrast-enhanced multi-slice computed tomography (MSCT), the subclinical perioperative stroke rate (as detected on diffusion-weighted magnetic resonance imaging (DW-MRI)) can be reduced by modification of the operative strategy if necessary.

The primary objective is to assess whether the use of pre-operative MSCT will reduce subclinical stroke rates (i.e., ischemic brain lesions) as identified with the use of DW-MRI after SAVR with or without concomitant CABG surgery.

The secondary objective is to assess whether the use of pre-operative MSCT will improve neurological assessment score, reduce clinical stroke, mortality, change in intervention strategy (pre- or intra-operatively), cannulation strategy and clamping strategy as well as reduce procedural times and improve quality of life (with the application of EQ-5D and KCCQ questionnaires).

This is a prospective, multicenter, parallel, open-label randomized controlled trial (RCT) with a 1:1 randomization including patients aged 18 years and older accepted for SAVR with or without concomitant CABG by the Heart Team at the St. Antonius Hospital Nieuwegein. All patients enrolled in the study will be randomized to additional pre-operative MSCT or no additional pre-operative MSCT. Postoperatively, a DW-MRI will be made in all patients. The trial will end after 30-day follow-up of all enrolled patients.

The main primary endpoint is the incidence of subclinical stroke rate (i.e., presence of new ischemic brain lesions) as identified with the use of DW-MRI made within one week postoperatively or before discharge. Secondary endpoints include the National Institutes of Health Stroke Scale (NIHSS) score within one week postoperatively (targeted at day two postoperatively), clinical ischemic stroke (conform VARC-3),transient ischemic attack diagnosed by a neurologist within one week postoperatively, defined by transient focal neurological signs or symptoms lasting \< 24 h presumed to be due to focal brain, spinal cord or retinal ischemia, but without evidence of acute infarction by neuroimaging or pathology, or with no imaging performed (conform VARC-3), mortality at discharge (normally at three to five days postoperatively) or within one week postoperatively (if discharge is \> 1 week postoperatively) and at three months postoperatively, the change in intervention strategy, the change in cannulation strategy, the change in clamping strategy, procedural times and the quality of life at three months postoperatively (assessed by EQ-5D and KCCQ)

When severe calcification of the ascending aorta is identified preoperatively on multi-slice computed tomography (MSCT), the operative strategy can be modified if necessary. This could possibly prevent stroke or even mortality in the study patients randomized to additional pre-operative MSCT. The MSCT will take 5-10 minutes. Only low-dose contrast-enhanced CT will be used, which results in a very low radiation risk. With application of too high dosages of contrast, there is a slight chance of kidney insufficiency. Furthermore, an allergic reaction to contrast could occur. However, patients with known allergies to contrast and patients with low renal function will be excluded from participation in this trial.

The patients receiving a preoperative CT-scan will have to be informed about all incidental findings found on the CT-scan. A possible disadvantage is found in the additional costs of a CT-scan, but the costs associated with stroke would outweigh the costs of a preoperative CT-scan. All patients will receive a DW-MRI before discharge. Contra-indications for MRI include pacemaker wires or implantable cardioverter defibrillators (ICDs), metallic implants, cochlear/ear implants, Swan-Ganz catheter, claustrophobia and contrast allergy. The presence of an aortic valve prosthesis is not a contra-indication for DW-MRI scanning.

All patients will be asked to fill out a questionnaire at baseline and within 90 days postoperatively. Since this will soon be implemented as part of standard care, the latter is not seen as extra burden for the patients.

Eligibility criteria: Inclusion Criteria:

* Primary symptomatic severe aortic valve stenosis (defined as an aortic valve area of \<1.0cm2 and either a mean valve gradient of at least 40mmHg or a peak velocity of at least 4.0 m/s)
* Accepted for SAVR (either planned to be done by a limited access approach (partial J-shaped sternotomy or right anterior thoracotomy or conventional median sternotomy approach at the preference of the patient and/or the discretion of the surgeon) with or without concomitant CABG by the Heart Team
* Informed consent

Exclusion Criteria:

* Previous aortic valve replacement
* Emergency procedure
* Pregnant women
* Renal failure (eGFR \<30 ml/min.)
* Known contrast allergy
* Patient unwilling to be informed about unrequested findings on the CT scan or DW-MRI scan
* Contra-indication for MRI (e.g. permanent pacemaker or ICD that can not be inactivated per order of the pacemaker or ICD technician, morphine or insulin pump, neurostimulator). All patients will fill out a MRI checklist to additionally check for (new) safety contra-indications for MRI.
* Patient who did not agree to the informed consent and/or refused to participate
* Patient unable to understand the informed consent/study

Primary outcomes:
measure: Subclinical stroke rate
timeFrame: Within 90 days post procedure
Secondary outcomes:
measure: National Institutes of Health Stroke Scale
timeFrame: within one week postoperatively (targeted at day two postoperatively)
measure: Clinical ischemic stroke (conform VARC-3)
timeFrame: Within one week postoperatively
measure: TIA diagnosed by a neurologist
timeFrame: One week postoperatively
measure: Change in intervention strategy
timeFrame: After hospital admission but before the end of surgery
measure: Change in cannulation strategy
timeFrame: During procedure
measure: Change in clamping strategy
timeFrame: During procedure
measure: Procedural times
timeFrame: During procedure
measure: Quality of life at three months postoperatively (assessed by EQ-5D and KCCQ)
timeFrame: At baseline (prior to procedure) and 90 days post procedure
Other outcomes:
Locations:
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital
state: Utrecht
Study officials:
affiliation: St. Antonius Hospital
name: Patrick Klein, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Antonius Hospital
name: Prof. Jurriën C ten Berg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Antonius Hospital
name: Martin C Swaans, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: