Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000696897
Ethics application status
Approved
Date submitted
17/03/2021
Date registered
7/06/2021
Date last updated
13/09/2023
Date data sharing statement initially provided
7/06/2021
Date results information initially provided
13/09/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
To assess if the administration of a clot busting medication (Tenecteplase) administered at the site of the clot in the brain following intravenous administration of the clot busting medication is safe and feasible in patients with acute ischaemic stroke within 4.5 hours of symptom onset.
Scientific title
Safety and Feasibility of Intravenous Tenecteplase thrombolysis plus Intra-arterial (IA) Tenecteplase thrombolysis in ischaemic stroke patients with medium vessel occlusion (distal M2, 3, 4, ACA, PCA).
Secondary ID [1] 303724 0
Nil known
Universal Trial Number (UTN)
Trial acronym
MOSS – Medium vessel Occlusion Stroke Study
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Ischaemic stroke 321150 0
Condition category
Condition code
Stroke 318953 318953 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intravenous thrombolysis: Patients will receive intravenous tenecteplase (TNK) 0.25mg/kg (maximum 25mg) administered as a bolus over 10 seconds within 4.5 hours of stroke onset. The dose of the intravenous treatment is individualised (weight dependent).
This will be followed by a digital substraction angiography (DSA) performed by a certified neurointerventionalist within 6 hours of stroke onset. The DSA itself without intervention has usually takes 20 minutes.
Patients will have arterial puncture of the femoral or the radial artery and sheath inserted and cerebral angiography performed under local anaesthesia. If the target lesion is confirmed on angiography to be more suitable for mechanical thrombectomy (depending on the diameter of the target occluded vessel) then a standard thrombectomy will be performed and the patient will be excluded from the study. A guide catheter will be navigated to the proximal artery either Carotid Artery or vertebral artery. A microcatheter will be navigated to the target vessel. The positioning of the microcatheter will be at the discretion of the operator but will ideally be directly in the target occluded vessel. If a target lesion is confirmed on angiography to be unsuitable for standard mechanical thrombectomy then the patient will progress to intra-arterial (IA) administration of TNK 1-3mg via a microcatheter. The dose of the intra-arterial TNK administration will be dependent on radiological evidence of reperfusion of the vessel. It will be administered in 1mg decrements, but not more than 3mg total dose.
This is a one-time treatment with an average duration of 40-60 minutes.
The decision against standard mechanical thrombectomy and for intra-arterial TNK administration within the study is based on the individual's vessel occlusion demonstrated on angiogram. The decision for standard mechanical thrombectomy is an exclusion from the study and the patient will be withdrawn from the study and will receive standard follow up care. The position of the clot and vascular access are influencing this decision. Usually a clot size of 8mm and more will lead to thrombectomy. The mechanical thrombectomy may require the induction of general anaesthesia. Standard mechanical thrombectomy has an intra-procedural risk of vessel rupture due to mechanical manipulation which increases with smaller size of the target vessel. The average duration of a mechanical thrombectomy is 1.5 hours and will be performed by a certified neurointerventinalist.
We will be auditing the study medication use and every procedure performed in accordance to the protocol.
Intervention code [1] 320332 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 326880 0
Proportion of patients with medium vessel recanalisation on MRI-DWI (diffusion weighted imaging) or CT perfusion without symptomatic intracerebral haemorrhage (sICH) at 24 hrs.
Timepoint [1] 326880 0
24 hours post treatment
Secondary outcome [1] 392949 0
Modified Rankin Scale (mRS) score at 3 months
Timepoint [1] 392949 0
3 months post treatment
Secondary outcome [2] 392951 0
Proportion of patients recanalised at time of angiography (before IA TNK) demonstrated radiologically by open vessel during angiography
Timepoint [2] 392951 0
At the conclusion of angiography
Secondary outcome [3] 394355 0
Proportion of patients reaching NIHSS (National Institutes of Health Stroke Scale) score 0-1 and mRS 0–1 or no change from baseline at 3 months
Timepoint [3] 394355 0
At the conclusion of study at 3 months
Secondary outcome [4] 394356 0
mRS 0–2 or no change from baseline at 3 months
Timepoint [4] 394356 0
3 months post treatment
Secondary outcome [5] 394357 0
Home time (number of days spent at home up to Day 90) as per patient interview
Timepoint [5] 394357 0
3 months post treatment
Secondary outcome [6] 394358 0
Length of stay in hospital as per medical records
Timepoint [6] 394358 0
At discharge
Secondary outcome [7] 394359 0
Death due to any cause
Timepoint [7] 394359 0
3 months post treatment
Secondary outcome [8] 394360 0
Proportion of patients reaching NIHSS 0-1 at Day 3
Timepoint [8] 394360 0
Day 3 post treatment
Secondary outcome [9] 394361 0
Symptomatic intracerebral haemorrhage (sICH) as per radiological scans
Timepoint [9] 394361 0
Day 3 post treatment
Secondary outcome [10] 394362 0
Ischaemic core volume at 24hr as per radiological scans (MRI or CT Perfusion)
Timepoint [10] 394362 0
24 hours post treatment

Eligibility
Key inclusion criteria
1. Patients presenting with acute ischaemic stroke eligible using standard criteria to receive IV thrombolysis within 4.5 hours of stroke onset.
2. Patient’s age is 18 years or over
3. Intra-arterial clot retrieval treatment can commence (arterial puncture) within 6 hours of stroke onset.
4. Willing to provide written (or oral) informed consent.
Imaging inclusion Criteria
5. Arterial occlusion on CT-Angiogram or MR-Angiogram of distal MCA (middle cerebral artery) branches (M2, 3, 4), ACA (anterior cerebral artery) or PCA (posterior cerebral artery) or corresponding CT-perfusion deficit
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Intracranial haemorrhage (ICH) identified by CT or MRI
2. Rapidly improving symptoms at the discretion of the Investigator.
3. Pre-stroke mRS equal to or greater than 4
4. Contraindication to imaging with contrast agents
5. Any terminal illness such that patient would not be expected to survive more than 1 year.
6. Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study.
7. Pregnant women.

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



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis
Simon's two-stage design will be used. In the first stage, 5 patients will be accrued. If there are no or one response in these 5 patients, the study will be stopped. Otherwise, 13 additional patients will be accrued for a total of 18. The null hypothesis will be rejected if 7 or more responses are observed in 18 patients.
Dichotomous outcomes will be presented as proportions and 95% confidence limits. Continuous outcomes will be presented as mean (standard deviation) or median (range) as appropriate. Analysis of variance will be used to assess gender-related difference in 3-month mRS. R software will be used for analysis.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
21/06/2021
Actual
3/08/2021
Date of last participant enrolment
Anticipated
2/06/2023
Actual
13/07/2022
Date of last data collection
Anticipated
30/09/2024
Actual
8/09/2022
Sample size
Target
18
Accrual to date
Final
3
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 18937 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 33444 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 308132 0
Hospital
Name [1] 308132 0
Royal North Shore Hospital
Country [1] 308132 0
Australia
Primary sponsor type
Government body
Name
Northern Sydney Local Health District
Address
Royal North Shore Hospital
Reserve Road
St Leonards NSW 2065
Country
Australia
Secondary sponsor category [1] 308893 0
None
Name [1] 308893 0
Address [1] 308893 0
Country [1] 308893 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308119 0
Northern Sydney Health District Human Research Ethics Committee
Ethics committee address [1] 308119 0
Kolling Building, Royal North Shore Hospital
Reserve Road
St Leonards NSW 2065
Ethics committee country [1] 308119 0
Australia
Date submitted for ethics approval [1] 308119 0
23/11/2020
Approval date [1] 308119 0
01/02/2021
Ethics approval number [1] 308119 0
2020/ETH02394

Summary
Brief summary
This study aims to assess if the administration of a clot busting medication (tenecteplase) administered at the site of the clot in the brain following intravenous administration of the clot busting medication is safe and feasible in patients with acute ischaemic stroke within 4.5 hours of symptom onset.

The approach in our study is to carefully select the patients with disabling strokes within hours of their symptoms commencing. If the clot can be dissolved at this point the damage to the brain can be prevented.

Patients will receive the treatment with a clot busting medication (tenecteplase) shown in multiple trials to be likely more effective and at least as safe in opening up brain vessels compared to the standard medication used. This is followed by an angiography and if the clot is still present and visualised in a medium sized vessel, which is deemed too small to be treated with mechanical removal, a small dose of the same clot busting medication will be administered directly into the clot. (These patients are still at risk of having disabling stroke deficits if the vessel cannot be reopened.)
The administration of a clot busting medication directly at the site of the clot in the brain has been safely tested in multiple trials, but not targeting the specific patient group as in our study.

The participants will be monitored for their immediate stroke symptom outcomes and followed up until three months after their stroke for any disabling effects. We will assess if the participants are able to return to their pre-stroke function and lifestyle.

This is a pilot study including 18 patients with the expectation that it will be followed by a larger trial involving multiple centres comparing this intervention with a group receiving the current standard treatment.

We hypothesise that the administration of a clot busting medication directly into the clot is safe will lead to better outcomes in stroke patients who are not suitable for the standard therapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 109602 0
Dr Miriam Priglinger
Address 109602 0
Royal North Shore Hospital
Department of Neurology
Reserve Road
St Leonards NSW 2065
Country 109602 0
Australia
Phone 109602 0
+61 405808879
Fax 109602 0
+61 2 946 31071
Email 109602 0
miriam.priglinger@health.nsw.gov.au
Contact person for public queries
Name 109603 0
Ms Susan Day
Address 109603 0
Royal North Shore Hospital
Department of Neurology
Reserve Road
St Leonards NSW 2065
Country 109603 0
Australia
Phone 109603 0
+61 2 946 31732
Fax 109603 0
+61 2 946 31071
Email 109603 0
susan.day@health.nsw.gov.au
Contact person for scientific queries
Name 109604 0
Dr Miriam Priglinger
Address 109604 0
Royal North Shore Hospital
Department of Neurology
Reserve Road
St Leonards NSW 2065
Country 109604 0
Australia
Phone 109604 0
+61 2 946 31733
Fax 109604 0
+61 2 946 31071
Email 109604 0
miriam.priglinger@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified epidemiological data, imaging findings and intervention results
When will data be available (start and end dates)?
After publication of our study up until one year after publication
Available to whom?
On discretion of the principal investigators to researchers who provide a methodically sound proposal
Available for what types of analyses?
For meta-analyses
How or where can data be obtained?
By contact to the principal investigator (miriam.priglinger@health.nsw.gov.au)


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Basic resultsNo 381636-(Uploaded-15-08-2023-16-04-26)-Basic results summary.docx
Plain language summaryNo All three participants received intra-arterial clo... [More Details]

Documents added automatically
No additional documents have been identified.