Comparing x-ray to artificial intelligence guidance in keyhole aortic aneurysm surgery
| ISRCTN | ISRCTN13832085 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13832085 |
| IRAS number | 280257 |
| Secondary identifying numbers | IRAS 280257, CPMS 51711 |
- Submission date
- 22/11/2021
- Registration date
- 03/12/2021
- Last edited
- 09/07/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Circulatory System
Plain English Summary
Current plain English summary as of 24/01/2022:
An aortic aneurysm is an abnormal swelling of the largest artery of the body, the aorta. As the aneurysm continues to enlarge, there is a risk that it can burst. To prevent this from happening, a device called a stent-graft, which is a metal frame (stent) with a special fabric covering (graft) is introduced within the aorta in a key-hole procedure called endovascular aneurysm repair (EVAR). This is a relatively common procedure with about 5,000 patients undergoing this procedure each year in the UK. The stent-grafts are selected for each patient before the operation using the information from highly detailed three-dimensional (3D) images from a CT scan. However, during the operation, only two-dimensional (2D) X-ray images are used to correctly position the stent-graft, which have less information than the 3D images. Cydar EV is a state-of-the-art software system that uses the 3D images from the CT scan to help select the right sized stent-graft for the patient and joins these images with the 2D X-ray images used during the operation in a process called image fusion. Cydar EV gives the doctor advanced guidance during the operation by using all the benefits of the 3D information. This study will compare operations performed using 2D X-rays (current standard of care) with operations using Cydar EV image guidance. This research will involve 340 patients at ten hospitals across the UK and examine if Cydar EV image guidance makes the operation easier and therefore quicker for the doctors to perform. Patients may benefit from a shorter time under anaesthetic, fewer harmful X-rays and less X-ray dye used during the procedure.
Who can participate?
Patients aged 18 and over who are undergoing endovascular (keyhole) aortic aneurysm repair
What does the study involve?
Participants will be randomly assigned to either one of two groups. One group will undergo the EVAR operation using 2D X-ray imaging alone, this is the standard way this operation is done in the UK. The other group will undergo the operation with their doctor using Cydar EV. During the operation details about the operation will be recorded including radiation dose, time taken and what and how many stents and other equipment is used. Regardless of which group the patients are in, they will have a post-operative CT scan to check the position of the stent as well as an outpatient clinic appointment at 4-12 weeks and 1 year after the stent is inserted. At the time of the operation and at both postoperative clinic appointments they will be given a short questionnaire asking them questions about their quality of life. This questionnaire takes about 5 minutes to complete and is an addition to the normal practice at their centre; it allows the research team to look at if there are any differences seen between the two groups in this study.
What are the possible benefits and risks of participating?
This research has been funded by the National Institute of Health Research (NIHR) as it is thought that it can benefit both patients and the NHS. Cydar EV, the technology behind this research, has already been shown in smaller studies to roughly halve the radiation exposure to patients and significantly reduce the length of the procedure and the amount of anaesthetic received by patients. It is also possible that the technology may help to place stent-graft more accurately. This research will help to answer if this technology is clinically and cost-effective and can therefore benefit patients and the NHS.
In terms of disadvantages, all patients taking part in this study will have slightly longer clinical appointments (by about 5-10 minutes) to allow time to complete the quality-of-life questionnaire (six brief questions). All patients taking part in the study will have two CT scans after their operation. In the UK, patients will have either one or two CT scans after a similar operation, depending on the hospital and type of stent-graft used for the procedure. This means that a patient may have the same number of CT scans, or one extra scan compared to someone not taking part in this study. These CT scans use ionising radiation to form images of the body. Ionising radiation may cause cancer many years or decades after the exposure. We are all at risk of developing cancer during our lifetime. 50% of the population is likely to develop one of the many forms of cancer at some stage during our lifetime. Taking part in this study is assumed to only add a very small chance of this happening.
Where is the study run from?
King's Trial Unit (UK)
When is the study starting and how long is it expected to run for?
August 2021 to November 2025
Who is funding the study?
National Institute for Health Research (NIHR) (UK)
Who is the main contact?
Dr Rachel Clough, rachel.clough@kcl.ac.uk
Contact information
Scientific
Department of Biomedical Engineering
The School of Biomedical Engineering & Imaging Sciences
3rd Floor Lambeth Wing, St Thomas' Hospital
King's College London
London
SE1 7EH
United Kingdom
 ORCID ID |
0000-0002-4243-6836 |
|---|---|
| Phone | +44 (0)20 7848 0532 |
| rachel.clough@kcl.ac.uk |
Public
King’s Clinical Trial Unit
Denmark Hill
De Crespigny Park
London
SE5 8AF
United Kingdom
| ORCID ID |
0000-0001-7350-4873 |
|---|---|
| izabela.pilecka@kcl.ac.uk |
Study information
| Study design | Multi-centre open-label two-armed randomized controlled clinical trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | A randomised controlled trial to assess the clinical-, technical- and cost-effectiveness of a cloud-based, ARtificially Intelligent image fusion system in comparison to standard treatment to guide endovascular Aortic aneurysm repair (ARIA) |
| Study acronym | ARIA |
| Study hypothesis | A randomised controlled trial to assess the clinical, technical and cost-effectiveness of a cloud-based, ARtificially Intelligent image fusion system in comparison to standard treatment to guide endovascular Aortic aneurysm repair (ARIA) |
| Ethics approval(s) |
Approved 10/02/2022, London – South East REC (Barlow House, 3rd Floor, 4 Minshull Street, Manchester, M1 3DZ, United Kingdom; +44 (0)207 104 8120; londonsoutheast.rec@hra.nhs.uk), ref: 22/LO/0081 |
| Condition | Abdominal aortic aneurysm |
| Intervention | Current intervention as of 24/01/2022: Participants will be randomised via the KCTU web-based randomisation system. Participants will be randomised to Cydar-EV image fusion for guidance or standard imaging techniques in a ratio of 1:1 post-consent and confirmation of eligibility. The allocation sequence will be generated dynamically using the method of minimisation. Minimisation will be balanced using the following factors: Surgeon: Surgeons from all sites 01, 02, 03, 04 etc. Procedure type: 01. Simple | 02. Complex Procedure urgency: 01. Emergency | 02. Elective Intervention: Patients will undergo endovascular aortic aneurysm repair using AI and computer vision (Cydar EV) for planning and surgical guidance, as per instructions for use. Cydar EV provides tools to: 1. Import and visualise CT data 2. Segment and annotate vascular anatomy from CT data 3. Place and edit virtual guidewires and measure lengths on them 4. Make measurements of anatomical structures on planar sections of the CT data 5. Produce an operative plan from measurements and segmentation of preoperative vessel anatomy 6. Overlay planning information such as preoperative vessel anatomy onto live fluoroscopic images, aligned based on the position of anatomical features present in both 7. Non-rigidly transform the visualisation of anatomy when intra-operative vessel deformation is observed 8. Postoperatively review data relating to procedures where the system was used Comparator: Patients will undergo endovascular aneurysm repair using standard technology and X-ray fluoroscopy imaging intra-operatively as defined under standard treatment above. The CT imaging for the patients randomised to standard treatment will be uploaded to Cydar EV at the time of randomisation, in case of cross-over. Intervention delivery: Procedures will be performed under local, regional or general anaesthesia (likely ratio: 1:1:8). Procedures can be undertaken using either a mobile C-arm in a surgical operating theatre, a dedicated fixed fluoroscopy set, or in a hybrid operating room. Patients may go to the ward, HDU or ITU according to local protocol. Routine pre-operative CT aortic imaging will be used to determine general suitability for endovascular repair, including assessment of landing zones for fixation and sealing, and procedure type and device selection. After randomisation in all patients the pre-randomisation CT images will be uploaded to Cydar EV. In the Cydar limb of the trial, Cydar EV will be used to plan the procedure including making appropriate measurements, map creation, procedural annotations, and device selection/verification. At operation, the Cydar equipment will be set up and switched on in theatre prior to ‘knife-to-skin’. The participant's information will have been pre-loaded to the system (according to ‘Cydar EV: Instructions for Use’) and will be available for selection. The machine must be positioned according to surgeon preference. Machine use will be recorded on the Cydar intervention record form. The patient’s information will be loaded on the system anytime up until the day of surgery prior to induction of the anaesthetic. Previous intervention: Participants will be randomised via the KCTU web-based randomisation system. Participants will be randomised to Cydar-EV image fusion for guidance or standard imaging techniques in a ratio of 1:1 post-consent and confirmation of eligibility. The allocation sequence will be generated dynamically using the method of minimisation. Minimisation will be balanced using the following factors: Surgeon: Surgeons from all sites 01, 02, 03, 04 etc. Disease extent: 01. AAA | 02. TAAA Procedure type: 01. Emergency | 02. Elective Intervention: Patients will undergo endovascular aortic aneurysm repair using AI and computer vision (Cydar EV) for planning and surgical guidance, as per instructions for use. Cydar EV provides tools to: 1. Import and visualise CT data 2. Segment and annotate vascular anatomy from CT data 3. Place and edit virtual guidewires and measure lengths on them 4. Make measurements of anatomical structures on planar sections of the CT data 5. Produce an operative plan from measurements and segmentation of preoperative vessel anatomy 6. Overlay planning information such as preoperative vessel anatomy onto live fluoroscopic images, aligned based on the position of anatomical features present in both 7. Non-rigidly transform the visualisation of anatomy when intra-operative vessel deformation is observed 8. Postoperatively review data relating to procedures where the system was used Comparator: Patients will undergo endovascular aneurysm repair using standard technology and X-ray fluoroscopy imaging intra-operatively as defined under standard treatment above. The CT imaging for the patients randomised to standard treatment will be uploaded to Cydar EV at the time of randomisation, in case of cross-over. Intervention delivery: Procedures will be performed under local, regional or general anaesthesia (likely ratio: 1:1:8). Procedures can be undertaken using either a mobile C-arm in a surgical operating theatre, a dedicated fixed fluoroscopy set, or in a hybrid operating room. Patients may go to the ward, HDU or ITU according to local protocol. Routine pre-operative CT aortic imaging will be used to determine general suitability for endovascular repair, including assessment of landing zones for fixation and sealing, and procedure type and device selection. After randomisation in all patients the pre-randomisation CT images will be uploaded to Cydar EV. In the Cydar limb of the trial, Cydar EV will be used to plan the procedure including making appropriate measurements, map creation, procedural annotations, and device selection/verification. At operation, the Cydar equipment will be set up and switched on in theatre prior to ‘knife-to-skin’. The participant's information will have been pre-loaded to the system (according to ‘Cydar EV: Instructions for Use’) and will be available for selection. The machine must be positioned according to surgeon preference. Machine use will be recorded on the Cydar intervention record form. The patient’s information will be loaded on the system anytime up until the day of surgery prior to induction of the anaesthetic. |
| Intervention type | Device |
| Pharmaceutical study type(s) | Not Applicable |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Cydar EV |
| Primary outcome measure | Procedure time, measured as the time between insertion of the first wire (after percutaneous access achieved, if applicable) at the beginning of the endovascular procedure to the last frame of the completion angiogram. This will be recorded (in minutes) at the time of the procedure by the local research team. |
| Secondary outcome measures | Current secondary outcome measures as of 24/01/2022: 1. Procedural efficiency: 1.1. Anaesthetic duration – the time between the beginning of induction and the end of emergence. This will be documented at the time of the procedure by the local research team in minutes. 1.2. X-ray dose per procedure – fluoroscopy time (FT) (seconds), dose area product (DAP) (Gy.cm2) and cumulative air kerma (CAK) (mGy) should be recorded and documented at the time of the procedure by the local research team. The imaging system used should also be recorded. 1.3. Contrast dose per procedure – the volume (ml) and concentration (mgI/ml) of the iodinated contrast material used should be recorded by the local research team at the time of the procedure in minutes. 1.4. Consumable use in the operating theatre for endovascular aortic aneurysm repair – the name of device, unit and quantity used, blood products used; details to be completed by nurse in the operating theatre or research nurse at the time of the procedure using a Source Data Worksheet. 2. Technical success: 2.1. Proximal and distal seal zone at least 10 mm and no evidence of endoleak. This will be documented by the imaging CoreLab team on review of the CT images acquired postoperatively and at 4-12 weeks and at 52 weeks. 3. Patient outcomes: 3.1. Length of ITU/HDU admission – date and time from admission to date and time of discharge from ITU/HDU; documented by the local research team during the time of admission; ITU and HDU admissions should be documented separately 3.2. Postoperative length of hospital stay – date of procedure to date of discharge from hospital (nights); documented by the local research team during the time of admission. 3.3. 30-day mortality – death of the participant within 30 days of the primary procedure; documented by the local research team; to include date of death (dd/mm/yy) and cause. 3.4. Re-intervention – any procedure open surgical or endovascular undertaken within 1 year of the primary endovascular aortic aneurysm repair procedure (binary outcome). The type, timing and number of procedures should also be recorded by the local research team. 3.5. Adverse events – hospitalisation for any reason within 1 year of the primary endovascular aortic aneurysm repair; the type of event should be documented and classified as one of the following: musculoskeletal, urological, neurological, ophthalmological, cardiovascular, gastro-intestinal, hepato-pancreato-biliary, dermatological or other by the local research team, with information captured to understand if linked to re-intervention (section ‘i’ above). For each hospitalisation the following should also be captured: 3.5.1. Day case, Elective, Non-elective 3.5.2. Length of hospital stay - date of admission to date of discharge (nights) 3.5.3. Length of ITU/HDU admission (if applicable) - date and time from admission to date and time of discharge from ITU/HDU; ITU and HDU admissions should be documented separately 3.6. Quality of life – differences in quality of life between intervention and the comparator group, and changes in quality of life post-surgery will be measured using data from the patient-completed EQ5D-3L instrument. EQ-5D-3L is a validated measure of health-related quality of life, consisting of a five-dimension health status classification system and a separate visual analogue scale. EQ-5D-3L data will be obtained through face-to-face or telephone interview with the participant at baseline, pre-discharge, 4-12 weeks and at 12-months follow up. Patients will complete the questionnaires with the support of the local research team 4. Cost-effectiveness, as assessed by: 4.1. Total resource use and costs assessed over the time horizon of the trial (12-months) 4.2. Quality-Adjusted Life Years (QALYs) - Quality of life will be measured by the EQ-5D-3L instrument as described above at baseline, pre-discharge, 4-12 weeks and at 12-months follow up. In order to be used in the calculation of quality‐adjusted life-years (QALYs), the EQ-5D-3L dimension scores will be converted to utilities using the relevant value set for England. Quality-adjusted life-years (QALYs) gained in both groups, over the time horizon of the trial, will be calculated using the area under the curve method. 4.3. Incremental cost per QALY between baseline and 12 month follow-up Previous secondary outcome measures: 1. Procedural efficiency: 1.1. Anaesthetic duration – the time between the beginning of induction and the end of emergence. This will be documented at the time of the procedure by the local research team in minutes. 1.2. X-ray dose per procedure – fluoroscopy time (FT) (seconds), dose area product (DAP) (Gy.cm2) and cumulative air kerma (CAK) (mGy) should be recorded and documented at the time of the procedure by the local research team. The imaging system used should also be recorded. 1.3. Contrast dose per procedure – the volume (ml) and concentration (mgI/ml) of the iodinated contrast material used should be recorded by the local research team at the time of the procedure in minutes. 1.4. Consumable use in the operating theatre for endovascular aortic aneurysm repair – the name of device, unit and quantity used, blood products used; details to be completed by nurse in the operating theatre or research nurse at the time of the procedure using a Source Data Worksheet. 2. Technical success: 2.1. Proximal and distal seal zone at least 10 mm and no evidence of endoleak. This will be documented by the imaging CoreLab team on review of the CT images acquired postoperatively and at 6-12 weeks and at 52 weeks. 3. Patient outcomes: 3.1. Length of ITU/HDU admission – date and time from admission to date and time of discharge from ITU/HDU; documented by the local research team during the time of admission; ITU and HDU admissions should be documented separately 3.2. Postoperative length of hospital stay – date of procedure to date of discharge from hospital (nights); documented by the local research team during the time of admission. 3.3. 30-day mortality – death of the participant within 30 days of the primary procedure; documented by the local research team; to include date of death (dd/mm/yy) and cause. 3.4. Re-intervention – any procedure open surgical or endovascular undertaken within 1 year of the primary endovascular aortic aneurysm repair procedure (binary outcome). The type, timing and number of procedures should also be recorded by the local research team. 3.5. Adverse events – hospitalisation for any reason within 1 year of the primary endovascular aortic aneurysm repair; the type of event should be documented and classified as one of the following: musculoskeletal, urological, neurological, ophthalmological, cardiovascular, gastro-intestinal, hepato-pancreato-biliary, dermatological or other by the local research team, with information captured to understand if linked to re-intervention (section ‘i’ above). For each hospitalisation the following should also be captured: 3.5.1. Day case, Elective, Non-elective 3.5.2. Length of hospital stay - date of admission to date of discharge (nights) 3.5.3. Length of ITU/HDU admission (if applicable) - date and time from admission to date and time of discharge from ITU/HDU; ITU and HDU admissions should be documented separately 3.6. Quality of life – differences in quality of life between intervention and the comparator group, and changes in quality of life post-surgery will be measured using data from the patient-completed EQ5D-3L instrument. EQ-5D-3L is a validated measure of health-related quality of life, consisting of a five-dimension health status classification system and a separate visual analogue scale. EQ-5D-3L data will be obtained through face-to-face or telephone interview with the participant at baseline, pre-discharge, 6-12 weeks and at 12-months follow up. Patients will complete the questionnaires with the support of the local research team 4. Cost-effectiveness, as assessed by: 4.1. Total resource use and costs assessed over the time horizon of the trial (12-months) 4.2. Quality-Adjusted Life Years (QALYs) - Quality of life will be measured by the EQ-5D-3L instrument as described above at baseline, pre-discharge, 6-12 weeks and at 12-months follow up. In order to be used in the calculation of quality‐adjusted life-years (QALYs), the EQ-5D-3L dimension scores will be converted to utilities using the relevant value set for England. Quality-adjusted life-years (QALYs) gained in both groups, over the time horizon of the trial, will be calculated using the area under the curve method. 4.3. Incremental cost per QALY between baseline and 12 month follow-up |
| Overall study start date | 01/08/2021 |
| Overall study end date | 15/11/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 340 |
| Total final enrolment | 364 |
| Participant inclusion criteria | Current participant inclusion criteria as of 24/01/2022: 1. Clinical diagnosis of abdominal aortic aneurysm (AAA) or thoracoabdominal aortic aneurysm (TAAA) suitable for endovascular treatment, as determined by CT imaging and multidisciplinary review by treating team 2. Fit for endovascular repair as determined by the operating team 3. CT imaging must be in accordance with ‘Cydar EV: Instructions for Use’ i.e. scans should have the same slice thickness and intervals as the original scan acquisition, must not have any missing slices or discontinuities, must include the pelvis and whole vertebrae including the spinous processes and must not use gantry tilt (this will be done post-consent) 4. Written informed consent (patients lacking capacity or unable to speak English will not be enrolled) 5. Age 18 years and above at the time of consent Previous participant inclusion criteria: 1. Clinical diagnosis of abdominal aortic aneurysm (AAA) or thoracoabdominal aortic aneurysm (TAAA) suitable for endovascular treatment, as determined by CT imaging and multidisciplinary review by treating team 2. Fit for endovascular repair as determined by the operating team 3. CT imaging must be in accordance with ‘Cydar EV: Instructions for Use’ i.e. scans should have the same slice thickness and intervals as the original scan acquisition, must not have any missing slices or discontinuities, must include the pelvis and whole vertebrae including the spinous processes and must not use gantry tilt (this will be done post-consent) 4. Written informed consent (patients lacking capacity will not be enrolled) 5. Age 18 years and above at the time of consent |
| Participant exclusion criteria | Current participant exclusion criteria as of 24/01/2022: Patients unable to provide written informed consent _____ Previous participant exclusion criteria: Patients with known connective tissue disease |
| Recruitment start date | 01/02/2022 |
| Recruitment end date | 30/01/2024 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Leeds
LS1 3EX
United Kingdom
South Wharf Road
London
W2 1BL
United Kingdom
Liverpool
L7 8XP
United Kingdom
Brighton, East Sussex
BN2 5BE
United Kingdom
Southampton
SO16 6YD
United Kingdom
Derby
DE22 3NE
United Kingdom
Manchester
M13 9WL
United Kingdom
Bristol
BS10 5NB
United Kingdom
Frimley
Camberley
GU16 7UJ
United Kingdom
London
SE1 7EH
United Kingdom
Taunton
TA1 5DA
United Kingdom
Sponsor information
University/education
Strand
London
WC2R 2ND
England
United Kingdom
| Phone | +44 (0)2078483224 |
|---|---|
| reza.razavi@kcl.ac.uk | |
| Website | http://www.kcl.ac.uk/index.aspx |
"ROR" |
https://ror.org/0220mzb33 |
Industry
Bulbeck Mill
Barrington
CB22 7QY
England
United Kingdom
| Phone | +44 (0)1223 778020 |
|---|---|
| cedarpreservationltd@outlook.com |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 15/11/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | It is intended that the results of the study will be reported and disseminated at international conferences and in peer-reviewed scientific journals. Recruiting sites will be informed of the results and will be asked to disseminate the findings to participants. Patient groups will be informed of the results for dissemination among their members. The researchers will publish the protocol in due course. |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 1.2 | 10/10/2022 | 18/04/2023 | No | No |
| Statistical Analysis Plan | version 1.0 | 30/06/2022 | 18/04/2023 | No | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol article | 25/03/2024 | 26/03/2024 | Yes | No |
Additional files
Editorial Notes
09/07/2024: The following changes were made to the trial record:
1. The overall end date was changed from 30/07/2024 to 15/11/2025.
2. The total final enrolment was added.
3. The intention to publish date was changed from 30/06/2025 to 15/11/2025.
26/03/2024: Publication reference added.
11/01/2024: The intention to publish date was changed from 30/06/2024 to 30/06/2025.
25/07/2023: The following changes have been made:
1. The recruitment end date was changed from 30/07/2023 to 30/01/2024.
2. Musgrove Park Hospital was added to the study participating centres.
18/04/2023: The following changes have been made:
1. Protocol file uploaded.
2. SAP file uploaded.
3. The ethics approval has been added.
24/01/2022: The following changes have been made:
1. The intervention has been updated.
2. The secondary outcome measures have been updated.
3. The participant inclusion criteria have been updated.
4. The participant exclusion criteria have been updated.
5. The plain English summary has been updated.
11/01/2022: The recruitment start date was changed from 01/01/2022 to 01/02/2022.
11/01/2022: The CPMS number was added to the protocol/serial no. field.
01/12/2021: Trial's existence confirmed by the NIHR.
