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.

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).

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12621000696897

Acronym

MOSS – Medium vessel Occlusion Stroke Study

Enrollment

Registered

2021-06-07

Start date

2021-08-03

Completion date

2022-07-13

Last updated

2023-09-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

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.

Interventions

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.

Study design

Allocation

Non-randomised trial

Intervention model

Single group

Primary purpose

Treatment

Masking

Open (masking not used)

Eligibility

Sex/Gender

All

Age

18 Years to No maximum

Healthy volunteers

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

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.

Outcome results