Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001604897p
Ethics application status
Not yet submitted
Date submitted
21/07/2021
Date registered
25/11/2021
Date last updated
25/11/2021
Date data sharing statement initially provided
25/11/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Carotid Stenosis Management During the COVID-19 Era
with Best Medical Intervention Alone (CASCOM Study)
Scientific title
Carotid Stenosis Management During the COVID-19 Era with Best Medical Intervention Alone (CASCOM Study): A prospective study of the rate of ipsilateral stroke in five risk-stratified cohorts of patients with at least 50% carotid artery stenosis
Secondary ID [1] 304828 0
Nil known
Universal Trial Number (UTN)
Nil known
Trial acronym
CASCOM Study
Linked study record
CASCOM Pilot Study: Carotid Stenosis Management During COVID-19 Era - Pilot Study (CASCOM-Pilot). Clinical Trials.gov Identifier: NCT04947046

Health condition
Health condition(s) or problem(s) studied:
Stroke prevention (ischaemic and haemorrhagic stroke) 322907 0
Arterial disease complication prevention 322908 0
Carotid stenosis 322909 0
Atherosclerosis 322910 0
Carotid artery stenting 322911 0
Carotid endarterectomy 322912 0
Medical intervention 322913 0
Non-stroke arterial disease complications 323999 0
Condition category
Condition code
Stroke 321505 321505 0 0
Ischaemic
Stroke 321681 321681 0 0
Haemorrhagic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The CASCOM Study intervention is current best practice medical intervention (lifestyle coaching and medication) for the prevention of stroke and other arterial disease complications. The primary aim of the CASCOM Study is to measure the rate of ipsilateral stroke, and other arterial disease complications, in individuals with advanced (50-99%) carotid stenosis who, for any reason, are managed using current best practice medical intervention alone.

5 patient cohorts will be studied:
1. Symptomatic patients with 50-99% (NASCET method) ipsilateral carotid Stenosis who would have been eligible for NASCET/ECST. These patients will be eligible for CASCOM Study primary analyses and hypothesis testing. (n= 367)
2. Patients with 60-99% (NASCET method) asymptomatic carotid stenosis who would have been eligible for ACAS. These patients will be eligible for CASCOM Study primary analyses and hypothesis testing. (n= 576)
3. Patients symptomatic within the last 6 months with 50-99% (NASCET method) ipsilateral carotid stenosis and would NOT have been eligible for NASCET/ECST. These patients will be eligible for CASCOM Study secondary analyses (outcome measure event rate measurements). (n= 200)
4. Patients symptomatic more than 6 months ago with 50-99% (NASCET method) ipsilateral carotid stenosis and would NOT have been eligible for NASCET/ECST. These patients will be Eligible for CASCOM Study Secondary Analyses (outcome measure event rate measurements). (n= 200)
5. Patients with 60-99% (NASCET method) asymptomatic carotid stenosis who would NOT have been eligible for ACAS. These patients will be eligible for CASCOM Study Secondary Analyses (outcome measure event rate measurements). (n= 200)

The medical intervention received by the study participants will be tailored to their arterial disease risk factor profile and based on our multinational expert review regarding how to best diagnose and ameliorate the leading arterial disease risk factors, including hypertension, hyperlipidaemia, atrial fibrillation, tobacco smoking, physical inactivity, excessive weight, hormonal status and diabetes. This review is comprehensive and incorporates key recommendations from guidelines.

The CASCOM Study expert review and summary of current best medical intervention for individuals with carotid stenosis will be published and distributed to all CASCOM Study investigators and participants. It will be used to guide and prompt clinicians and patients. It will be updated as advances are made. CASCOM Study investigators and participants will be informed in writing of advances as soon as possible.

Current best medical intervention will be delivered by CASCOM Study investigators to CASCOM Study participants during routine clinical assessments. Preference will be given to face-to-face assessments. However, telehealth assessments will be permissible if this is the best option at the time. Patient assessments will be performed at baseline, 1 month, 3 months and then every six months for as long as the study is running- which is a minimum of five years. Duration of consultations will reflect the individual patient need and stage of study follow-up.

Medications, route of administration and dosage and lifestyle interventions (such as advice in diet exercise and smoking cessation) will depend on an individual patient's risk factor profile and current best evidence as summarised in our multi-expert review on the subject. Patient adherence to taking medication as prescribed will be assessed using a simple two question multi-choice questionnaire at each CASCOM Study assessment.
Intervention code [1] 321205 0
Prevention
Intervention code [2] 321206 0
Treatment: Drugs
Intervention code [3] 321207 0
Lifestyle
Comparator / control treatment
The rate of ipsilateral stroke of symptomatic CASCOM Study participants will be compared with that reported in the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial (ECST). The rate of ipsilateral stroke of CASCOM Study participants with asymptomatic carotid stenosis will be compared with that reported in the Asymptomatic Carotid Atherosclerosis Study (ACAS). We will used publish aggregated data from the randomised trials for comparison purposes. Arterial disease risk factors are defined differently these days. It is highly unlikely that meaningful comparisons using individual patient data will be possible. What is most important, and possible, is to study the outcomes of the types of patients recruited into those randomised trials when given current best practice medical intervention alone.
Control group
Historical

Outcomes
Primary outcome [1] 328311 0
First ipsilateral stroke (with respect to the study artery).

Stroke is defined as rapidly developed clinical symptoms and/or signs of cerebral or retinal dysfunction lasting >24 hours or leading to death, with no apparent cause other than focal neurovascular origin. Strokes will be classified as fatal if thought to be the primary or main cause of death or lead to a complication (such a pneumonia or pulmonary embolus) that causes death.

All strokes will be assessed based on the clinical information captured by the CASCOM Study investigator-clinician and adherence to the stroke definition given above. Strokes will be subdivided into type by the brain imaging results. The outcome measure of all strokes in the CASCOM Study will be validated by at least two CASCOM Study investigators who are not from the CASCOM Study site where the patient (CASCOM Study participant) with stroke was being followed-up.
Timepoint [1] 328311 0
Within 5 years of CASCOM Study recruitment
Secondary outcome [1] 398561 0
Ipsilateral transient ischaemic attack (TIA) with respect to the CASCOM Study artery.

TIA is defined as rapidly developed clinical symptoms and/or signs of cerebral or retinal dysfunction lasting <24 hours with no apparent cause other than of focal neurovascular origin where resolution is swift and leaves no detectable permanent neurologic deficit.

All TIAs will be assessed based on the clinical information captured by the CASCOM Study investigator-clinician and adherence to the TIA definition given above.
Timepoint [1] 398561 0
Within 5 years of CASCOM Study recruitment.
Secondary outcome [2] 398562 0
Contralateral stroke (with respect to the CASCOM Study artery)

Stroke is defined as rapidly developed clinical symptoms and/or signs of cerebral or retinal dysfunction lasting >24 hours or leading to death, with no apparent cause other than focal neurovascular origin. Strokes will be classified as fatal if thought to be the primary or main cause of death or lead to a complication (such a pneumonia or pulmonary embolus) that causes death.

All strokes will be assessed based on the clinical information captured by the CASCOM Study investigator-clinician and adherence to the stroke definition given above. Strokes will be subdivided into type by the brain imaging results.
Timepoint [2] 398562 0
Within 5 years of CASCOM Study recruitment
Secondary outcome [3] 398563 0
Contralateral TIA with respect to the CASCOM Study artery

TIA is defined as rapidly developed clinical symptoms and/or signs of cerebral or retinal dysfunction lasting <24 hours with no apparent cause other than of focal neurovascular origin where resolution is swift and leaves no detectable permanent neurologic deficit.

All TIAs will be assessed based on the clinical information captured by the CASCOM Study investigator-clinician and adherence to the TIA definition given above.
Timepoint [3] 398563 0
Within 5 years of CASCOM Study recruitment
Secondary outcome [4] 398566 0
Myocardial infarction.

Myocardial infarction is defined as the detection of a rise or fall of cardiac biomarker values (preferably cardiac troponin) with at least one value above the 99th percentile upper reference limit and with at least one of the following:
- Symptoms of ischaemia (chest pain and/or shortness of breath and/or syncope due to cardiac arrest)
- New or presumed new significant ST segment–T wave changes or new left bundle branch block on the electrocardiograph (ECG)
- Development of pathological Q waves in the ECG
- Imaging evidence of new loss of viable myocardial tissue or new regional wall motion abnormality
- Identification of an intracoronary thrombus by angiography or autopsy

All myocardial infarctions will be assessed based on the clinical information captured by the CASCOM Study investigator-clinician and adherence to the myocardial infarction definition given above.
Timepoint [4] 398566 0
Within 5 years of CASCOM Study recruitment
Secondary outcome [5] 398567 0
Limb amputation due to arterial disease

All limb amputations will be assessed based on the clinical information captured by the CASCOM Study investigator-clinician and adherence to the concept of amputation and arterial disease.
Timepoint [5] 398567 0
Within 5 years of CASCOM Study recruitment
Secondary outcome [6] 398568 0
Death from any cause apart from stroke involving the brain or eye ipsilateral to the study carotid artery

All deaths will be assessed based on the clinical information captured by the CASCOM Study investigator-clinician and adherence to the concept of stroke (as defined above) and death.
Timepoint [6] 398568 0
Within 5 years of CASCOM Study recruitment

Eligibility
Key inclusion criteria
i. Stroke or TIA patient with 50-99% carotid stenosis ipsilateral to the implicated brain region/eye or patient with 60-99% asymptomatic carotid stenosis (using 'NASCET' or 'NASCET' equivalent criteria to measure stenosis severity).
ii. Age at least 18 years.
iii. Willing and able to consent and be followed up for at least 24 months.
iv. Life expectancy at least 24 months (therefore, a 9-Point Clinical Frailty Scale Score of 1-6).
v. Absence of stroke resulting in severe deficit (mRS >3 and/or no useful function on either side of the body).
vi. Absence of neurological, psychological or cognitive condition likely to impede recognition of cerebral or retinal stroke or TIA, including moderate or severe dementia, neurodegenerative disease with significant neurological impairment present or expected in the next 3 years).
vii. Stenosis of study carotid artery attributable to atherosclerotic disease.
viii. No previous ipsilateral carotid endarterectomy, carotid angioplasty or stenting, trans-carotid arterial revascularisation or other carotid artery procedure.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
None

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Not applicable
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
This is a prospective, nonrandomised, observational study of five risk-stratified cohorts of patients with advanced (50-99%) carotid stenosis.
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
We will separate CASCOM Study patients into those who would, and would not, have been eligible for past randomised trials of carotid endarterectomy (surgery) versus medical intervention alone.

We plan to study at least 367 symptomatic patients and at least 576 asymptomatic patients in the former randomised trial ’eligible’ category and use them for hypothesis testing. We expect at least a 50% lowering of stroke rates with medical intervention alone in the CASCOM Study compared to that seen in past randomised trials.

In addition, we plan to study 600 patients in the latter randomised trial ’ineligible’ category and report their ipsilateral stroke rate over 5 years of follow-up. Outcomes for such patients given medical intervention alone have never been properly measured and yet they often recommended to have a carotid artery procedure.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/07/2022
Actual
Date of last participant enrolment
Anticipated
30/06/2025
Actual
Date of last data collection
Anticipated
1/07/2030
Actual
Sample size
Target
1543
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA,VIC
Recruitment outside Australia
Country [1] 23978 0
Denmark
State/province [1] 23978 0
Country [2] 23979 0
United Kingdom
State/province [2] 23979 0
Country [3] 23980 0
United States of America
State/province [3] 23980 0
Country [4] 23981 0
Ireland
State/province [4] 23981 0
Country [5] 23982 0
Italy
State/province [5] 23982 0
Country [6] 23983 0
Greece
State/province [6] 23983 0
Country [7] 23984 0
Poland
State/province [7] 23984 0
Country [8] 23986 0
Croatia
State/province [8] 23986 0
Country [9] 23987 0
France
State/province [9] 23987 0
Country [10] 23988 0
Canada
State/province [10] 23988 0
Country [11] 23989 0
Russian Federation
State/province [11] 23989 0
Country [12] 23990 0
Czech Republic
State/province [12] 23990 0
Country [13] 23991 0
Nigeria
State/province [13] 23991 0
Country [14] 24293 0
Cyprus
State/province [14] 24293 0
Country [15] 24294 0
Saudi Arabia
State/province [15] 24294 0

Funding & Sponsors
Funding source category [1] 309201 0
Self funded/Unfunded
Name [1] 309201 0
Country [1] 309201 0
Primary sponsor type
University
Name
Monash University
Address
Wellington Rd, Clayton, VIC, 3800
Country
Australia
Secondary sponsor category [1] 310160 0
Charities/Societies/Foundations
Name [1] 310160 0
International Union of Angiology
Address [1] 310160 0
The registered office of the IUA is located at:
Collège Français de Pathologie Vasculaire,
Maison de l'Angiologie
18 rue de l'Université, 75007
Paris, France
Country [1] 310160 0
France

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 309054 0
Monash University
Ethics committee address [1] 309054 0
26 Sports Walk, Clayton, VIC, 3168
Ethics committee country [1] 309054 0
Australia
Date submitted for ethics approval [1] 309054 0
01/02/2022
Approval date [1] 309054 0
Ethics approval number [1] 309054 0

Summary
Brief summary
Background

Carotid endarterectomy (CEA) and carotid stenting (CAS) are often performed for subgroups of patients for whom procedural benefit has not been established in randomised trials and despite evidence of serious procedural risk. Furthermore, there is no current evidence of procedural benefit compared to optimal medical intervention alone (lifestyle coaching and medication) for any individuals. In some places, the COVID-19 pandemic has made it difficult or impossible to perform CEA and CAS.

Aim/Objectives

1. To measure the rate of ipsilateral (same-sided) stroke, and other arterial disease complications, in patients with advanced (50-99%) carotid stenosis who, for any reason, are managed using current best medical intervention alone. Reasons for a nonprocedural approach may include insufficient resources caused by the coronavirus pandemic, unproven procedural benefit, anticipated procedural futility and/or net harm, or patient refusal. We will study patients for whom carotid procedures are not possible or considered unethical and, therefore, where a randomised trial approach involving carotid procedures is inappropriate.

2. To compare the CASCOM Study rate of ipsilateral stroke for symptomatic patients with that reported in the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial (ECST), and the CASCOM Study rate of ipsilateral stroke associated with asymptomatic carotid stenosis with that reported in the Asymptomatic Carotid Atherosclerosis Study (ACAS).

Methods

CASCOM is a prospective cohort study of current best medical intervention alone for stroke prevention in people who become patients by way of their referral for carotid imaging by a medical practitioner. It is also a multi-national, multi-specialty, collaborative, quality assurance and evaluation project. We will separate patients into those who would, and would not, have been eligible for past randomised CEA trials. We plan to study >367 symptomatic patients and >576 asymptomatic patients in the former, ‘eligible’, category and use them for hypothesis testing. We expect at least a 50% lowering of stroke rates with medical intervention alone in the CASCOM Study compared to that seen in past randomised trials. In addition, we plan to study 600 patients in the latter randomised trial ‘ineligible’ category and report their ipsilateral stroke rate over 5 years of follow-up. We will use ‘REDCap’ (Research Electronic Data Capture) for case reporting.

Findings and Significance

In CASCOM we expect at least 50% lowering of the ipsilateral stroke rate compared to that seen with medical intervention alone in past randomised trials. If correct, CASCOM will provide new evidence that past randomised trials of CEA and CAS are outdated and elucidate new, improved standards for preventing stroke and other arterial disease complications.
Trial website
https://factcats.org/op1.php
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 112806 0
A/Prof Anne L. Abbott
Address 112806 0
Department of Neuroscience
Central Clinical School
Monash University
99 Commercial Rd
Melbourne
VIC 3004
Country 112806 0
Australia
Phone 112806 0
+61 3 9903 0304
Fax 112806 0
Email 112806 0
anne.abbott@monash.edu
Contact person for public queries
Name 112807 0
A/Prof Anne L. Abbott
Address 112807 0
Department of Neuroscience
Central Clinical School
Monash University
99 Commercial Rd
Melbourne
VIC 3004
Country 112807 0
Australia
Phone 112807 0
+61 3 9903 0304
Fax 112807 0
Email 112807 0
anne.abbott@monash.edu
Contact person for scientific queries
Name 112808 0
A/Prof Anne L. Abbott
Address 112808 0
Department of Neuroscience
Central Clinical School
Monash University
99 Commercial Rd
Melbourne
VIC 3004
Country 112808 0
Australia
Phone 112808 0
+61 3 9903 0304
Fax 112808 0
Email 112808 0
anne.abbott@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
The CASCOM Study REDCap database dictionary and de-identified individual CASCOM participant data.
When will data be available (start and end dates)?
The CASCOM Study REDCap database dictionary will be made public and freely available once the study is established. The de-identified CASCOM Study participant information will be available beginning six months and ending at least 5 years following publication of all data relevant to the CASCOM Study hypotheses.
Available to whom?
Sharing of de-identified CASCOM participant information carries responsibilities and will be arranged on request at the discretion of CASCOM Study investigators.
Available for what types of analyses?
De-identified individual CASCOM participant data will be available to other approved researchers who provide a methodologically sound research proposal.
How or where can data be obtained?
Via contacting CIA, A/Prof Anne Abbott: Anne.L.Abbott@gmail.com


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
12612Other    The CASCOM Study protocol is expected to be publis... [More Details]


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseExtra-Cranial Carotid Artery Stenosis: An Objective Analysis of the Available Evidence.2022https://dx.doi.org/10.3389/fneur.2022.739999
N.B. These documents automatically identified may not have been verified by the study sponsor.