Extending the time window for Tenecteplase by Effective RecanalizatioN of bAsilar artery occLusion in patients with POSTerior circulation stroke

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Regional Universitaire De Tours

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2024-11-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

PHRC national

External identifiers

EU CT number

2024-513444-28-00

ClinicalTrials.gov

NCT05105633

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective of the study is to test the hypothesis that the thrombolytic tenecteplase (TNK, 0.25mg/kg) administered within 24 hours after symptom onset ± thrombectomy, is superior to current best practice (alteplase, rtPA, 0.9mg/kg within 4.5 hours of stroke onset or standard care/no lysis ± thrombectomy) in achieving excellent functional outcome (mRS 0-1) or return to the premorbid modified Rankin Scale at 90 days in patients with acute ischaemic stroke due to basilar artery occlusion.

Secondary objectives 9

1. Good functional outcome, defined as a mRS 0 to 2 or return to baseline at 3 months.
2. Favourable functional outcome, defined as mRS 0 to 3 or return to baseline at 3 months.
3. Improvement on the mRS score (ordinal analysis of the mRS, merging category 5-6) at 3 months.
4. Early clinical improvement (reduction in acute -72 hour NIHSS score of ≥8 or 72 hour NIHSS 0-1).
5. Basilar recanalization (eTICI 2B-3) on digital subtraction angiography run prior to thrombectomy.
6. sICH defined as parenchymal haemorrhage type 2 (PH2), subarachnoid haemorrhage, and/or intraventricular haemorrhage within 36 of treatment, combined with a neurological deterioration of ≥4 points on the NIHSS from baseline, or leading to death.
7. A reduction of severe disability or death (mRS 5 – 6) at 3 months.
8. A reduction of mortality due to any cause at 3 and 12 months
9. A higher quality of life as assessed per the Quality-of-Life assessment (EQ-5D).

Conditions and MedDRA coding

Acute ischaemic stroke due to basilar artery occlusion.

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age ≥18
2. Patient presenting with posterior circulation ischaemic stroke symptoms due to partial or complete basilar artery occlusion within 24 hours from symptom onset (or clinical deterioration/coma) or the time the patient was last known to be well.
3. Presence of a basilar artery occlusion on CT Angiography or MR Angiography. Basilar artery occlusion will be defined as ‘potentially retrievable’ occlusion at the basilar artery. This can be a partial or complete occlusion.
4. Premorbid mRS≤3 (independent function or requiring only minor domestic assistance and able to manage alone for at least 1 week).
5. Affiliated to a French social security scheme or equivalent.
6. Written informed consent obtained from the participant, from her/his next of kin or trusted person. Use of the emergency inclusion procedure if a next of kin or trusted person cannot be contacted. When a subject is no longer incapacitated, informed consent to continue participation will be obtained from the subject.

Exclusion criteria 18

1. Intracerebral haemorrhage (ICH) or other diagnosis (e.g. tumour) identified by baseline imaging.
2. Posterior circulation Acute Stroke Prognosis Early CT score (pc-ASPECTS) <7 on non-contrast CT, CT Angiography source images or DWI MRI.
3. Significant cerebellar mass effect or acute hydrocephalus.
4. Established frank hypodensity on non-contrast CT indicating subacute infarction.
5. Established frank hyperintensity on MRI FLAIR sequences indicating subacute infarction or presence of other unfavourable imaging profile which is likely to be associated with an increased risk of haemorrhagic transformation at the investigator’s discretion.
6. Bilateral extensive brainstem ischaemia.
7. Strong suspicion of underlying intracranial atherosclerotic disease (e.g diffuse arterial calcifications, basilar stenosis) or dissection which may require immediate neuro-interventional procedure with intracranial stenting and not benefit from intravenous thrombolysis at investigator’s discretion.
8. Other standard contraindications to intravenous thrombolysis.
9. Contraindication to tenecteplase/alteplase (hypersensitivity to the active substance or to one of the excipients)
10. Contraindication to imaging with contrast agents.
11. Patient deprived of their liberty by judicial/administrative decision or subject to any legal protection measures (guardianship or trusteeship).
12. Clinically evident pregnant woman.
13. Current participation in another research drug treatment protocol.
14. Known terminal illness such that the patients would not be expected to survive a year.
15. 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.
16. Warfarin - thrombolysis can be used if point-of-care INR≤1.4 or laboratory INR≤1.7.
17. Dabigatran – If dabigatran is known or suspected to have been taken within last 48 hours then Idarucizumab 5g IV bolus should be given prior to thrombolysis.
18. Apixaban/Rivaroxaban - If Apixaban/Rivaroxaban is known to have been taken in last 12 hours then patient cannot be enrolled. If unclear, order urgent aPTT, INR, anti-Xa level: patient can be enrolled if appropriately calibrated anti-Xa level indicates <10 ng/mL apixaban or <100 ng/mL rivaroxaban.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion of patients with Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS (if baseline premorbid mRS =2-3) at 3 months.

Secondary endpoints 9

1. Proportion of patients with mRS 0-2 or return to baseline mRS at 3 months.
2. Proportion of patients with mRS 0-3 or return to baseline mRS at 3 months.
3. Ordinal analysis of the mRS, merging category 5-6, at 3 months.
4. Proportion of patients achieving early clinical improvement (reduction in acute –72 hour NIHSS score of ≥8 or 72 hour NIHSS 0-1).
5. Proportion of patients with complete occlusion at baseline who achieve eTICI 2b/3 [14] on initial digital subtraction angiography run prior to thrombectomy.
6. Proportion of patients with sICH defined as parenchymal haemorrhage type 2 (PH2), subarachnoid haemorrhage, and/or intraventricular haemorrhage within 36 of treatment, combined with a neurological deterioration of ≥4 points on the NIHSS from baseline, or leading to death.
7. Proportion of patients with mRS 5-6 at 90 days (severe disability or death).
8. All-cause mortality within 90 days.
9. Quality of Life assessment (EQ-5D) at 3 and 12 months.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Regional Universitaire De Tours

Sponsor organisation

Centre Hospitalier Regional Universitaire De Tours

Address

2 Boulevard Tonnelle

City

Tours Cedex 9

Postcode

37044

Country

France

Scientific contact point

Organisation

Centre Hospitalier Regional Universitaire De Tours

Contact name

Coordinating Investigator

Public contact point

Organisation

Centre Hospitalier Regional Universitaire De Tours

Contact name

Coordinating Investigator

Locations

1 EU/EEA country · 15 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications