Intra-arterial t-PA infusion during mechanical thrombectomy in acute ischemic stroke: a randomized trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vall D'hebron Institut De Recerca

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)

2024-05-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Vall d'Hebron Research Institute (VHIR)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective of this study is to determine whether the intra-arterial tPA infusion during mechanical thrombectomy (MT) might affect clinical and technical outcomes of patients with AIS due to LVO of the anterior circulation

Conditions and MedDRA coding

People with acute ischemic stroke (AIS) due to large vessel occlusion of the anterior circulation.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Informed consent as documented by signature. It could be also an oral consent and subsequently signed.
2. Age ≥18
3. Neurological deficit with a NIHSS of ≥6
4. Pre-treatment mRs ≤1
5. Patients eligible for endovascular treatment
6. For IVT: Patient within 9 hours of stroke onset according to locally accepted guidelines. Patients with a wake up stroke, may be included if other inclusion criteria are satisfied. The ‘wake up’ stroke is defined as having no symptoms at sleep onset, but stroke symptoms on waking. The time of stroke onset is to be taken as the mid-point between sleep onset (or last known to be normal) and time of waking. The maximum time window for randomization is then 9 hours from the mid-point as described.
7. Occlusion (TICI 0-1) of the intracranial internal carotid artery (ICA) and the M1 segments of the middle cerebral artery (MCA) confirmed by CT or MR angiography, accessible for MT
8. An ischemic core lesion volume ≤ 70 ml using MR-DWI or CT-CBF
9. A penumbral mismatch: a “hypo-perfusion to core” volume ratio of greater than 1.2 and an absolute difference greater than 10mL (using a MR or CT Tmax > 6 second delay) between perfusion lesion and MR-Diffusion Weighted Imaging (DWI) or CT- Cerebral Blood Flow (CBF) core lesion.
10. Patients admitted from a Secondary Stroke Center (SSC) eligible for EVT may be included in the VANISH protocol, if tPA infusion ended 40 minutes before a CT control, confirming the EVT indication

Exclusion criteria 12

1. Any absolute contraindication for IV or IA t-PA
2. Pregnancy or lactating women. A negative pregnancy test before randomization is required for all women with child-bearing potential.
3. Known (serious) sensitivity to radiographic contrast agents, nickel, titanium metals, or their alloys
4. Known renal disease
5. Severe comorbid condition with life expectancy less than 90 days at baseline
6. Known advanced dementia or significant pre-stroke disability (mRS≥2)
7. Foreseeable difficulties in follow-up due to geographic reasons (e.g. patients living abroad)
8. Comorbid disease or condition that would confound the neurological and functional evaluations or compromise survival or ability to complete follow-up assessments
9. Subject currently uses or has a recent history of illicit drug(s) or abuses alcohol (defined as regular or daily consumption of more than four alcoholic drinks per day).
10. Radiological confirmed evidence of mass effect or intracranial tumor (except small meningioma)
11. Radiological confirmed evidence of cerebral vasculitis
12. CTA or MRA evidence of tandem occlusions of any cause

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion of patients achieving a mRS 0-1

Secondary endpoints 7

1. The proportion of patients with dramatic clinical recovery (DCR). DCR will be defined as a decrease of ≥8 points from baseline NIHSS or a 24-hour NIHSS score ≤2.
2. The proportion of patients achieving a mRS 0-2
3. The proportion of hemorrhagic complications. A non-contrast CT will be performed after 24 to 48 hours to evaluate the presence and degree of hemorrhagic transformation according to the ECASS-II criteria[3].
4. The proportion of symptomatic intracerebral hemorrhage (sICH)
5. The proportion of death due to any cause
6. The proportion of patients who suffer a Safety Outcome. Safety outcome will be defined as the proportion of patients with the composite of: (i) symptomatic intracranial hemorrhage (ii) major bleeding due to access complications including groin hematoma, retroperitoneal hematoma (iii) contrast nephropathy.
7. The proportion of patients discharged at home with or without services

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vall D'hebron Institut De Recerca

Sponsor organisation

Vall D'hebron Institut De Recerca

Address

Passeig De La Vall D'hebron 119-129

City

Barcelona

Postcode

08035

Country

Spain

Scientific contact point

Organisation

Vall D'hebron Institut De Recerca

Contact name

Francesco Diana, M.D.

Public contact point

Organisation

Vall D'hebron Institut De Recerca

Contact name

Francesco Diana, M.D.

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Application history

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