“Intravenous Thrombolysis With Tenecteplase Plus Thrombectomy Versus Thrombectomy Alone In Patients With A Large Ischemic Stroke: A Multicentre Randomized Controlled Trial” THE IVT ALL IN TRIAL

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

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)

2026-03-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Ministry of Health, PHRC-N 2023

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To assess which treatment strategy between intravenous thrombolysis with tenecteplase plus thrombectomy and thrombectomy alone has a superior efficacy in terms of 3-month functional outcome for LVOS patients with large cores.

Secondary objectives 5

1. To compare between intravenous thrombolysis with tenecteplase plus thrombectomy and thrombectomy alone the rate of 3-month good functional outcome in the following subgroups: - Patients treated in a primary stroke centre without onsite MT versus a comprehensive stroke centre with onsite MT; - Patients with very large (ASPECTS 2-3) versus large (ASPECT 4-5) cores; - Patients treated within 4.5 hours versus others.
2. To compare intravenous thrombolysis with tenecteplase plus thrombectomy (bridging therapy) and thrombectomy alone in terms of: Clinical outcomes - early neurological improvement, defined as a ≥ 8-points decrease of the NIHSS score or a NIHSS score ≤ 1 at day 1 - 3-month functional independence (mRS score ≤ 2) - distribution of 3-month mRS scores - one-year independent ambulation (mRS score ≤ 3) - one-year functional independence (mRS score ≤ 2)
3. To compare intravenous thrombolysis with tenecteplase plus thrombectomy (bridging therapy) and thrombectomy alone in terms of:Radiological outcomes - successful, excellent and complete recanalisation rates defined as an extended Treatment In Cerebral Ischemia (eTICI) scores of 2b50/2b67/2c/3, 2c/3 and 3 respectively on the first angiographic run, after the first pass and at the end of the procedure - mean change in infarct volume from baseline at day 1, defined as: (day 1 volume) – (baseline volume)
4. To compare intravenous thrombolysis with tenecteplase plus thrombectomy (bridging therapy) and thrombectomy alone in terms of:Safety outcomes - early neurological worsening defined as a ≥ 4-point increase on the NIHSS score within 24 hours due to the stroke itself - intracranial hemorrhage (ICH) according to the Heidelberg Bleeding Classification - symptomatic ICH, scored according to the Heidelberg Bleeding Classification - 3-month and 1-year mortality - adverse events - serious adverse events
5. To compare intravenous thrombolysis with tenecteplase plus thrombectomy (bridging therapy) and thrombectomy alone in terms of: Incremental cost-utility ratio

Conditions and MedDRA coding

Adult patients with a LVOS with large core within 9 hours of symptoms onset or last seen well, or with a diffusion weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch in case of unknown onset.

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. ­ Age ≥ 18 years
2. ­ mRS ≤ 1 before stroke
3. ­ Anterior circulation LVOS eligible to MT within 24 hours of onset or unknown onset with a DWI-FLAIR mismatch
4. ­ Large core defined either as: - ASPECTS 2-5 or a core volume between 70 and 130 ml on MRI or perfusion CT for patients with process times compatible with IVT administration within 4.5 hours of onset or unknown onset with process times compatible with IVT administration within 4.5 hours of last seen well or unknown onset with a DWI-FLAIR mismatch - ASPECTS 2- 5 with a core volume ≤ 70 ml and core/perfusion mismatch > 1.2 for patients with process times compatible with IVT administration within 4.5 and 9 hours of onset, defined as the mid-point between last known to be normal and symptoms constatation in case of unknown onset
5. ­ Written informed consent signed by the patient or the trustworthy person / family member / close relative, or inclusion in case of emergency. (To note, in the latter case, written informed consent should be signed by the patient (if needed, by trustworthy person, family member or close relative) as soon as possible (article 35 of the European regulation N°536/2014)).

Exclusion criteria 9

1. ­Anterior circulation stroke with a distal occlusion not eligible to MT
2. ­ Posterior circulation stroke
3. ­ Pregnancy or breastfeeding woman
4. ­ Any contraindication to IVT other than those related to the NIHSS score upper limit, infarct size and symptoms-to-onset time, such as (but not limited to): * Persistent incapacity to lower blood pressure under 185/110 mmHg * Respiratory or hemodynamic failure * Externalized bleeding
5. ­ Any contra-indication to MT: * Contra-indication to femoral, radial or humeral arterial puncture * Allergy to iodinated contrast media * Known Renal insufficiency at inclusion time (confirmed biologically by a creatinine clearance < 30 ml/min calculated with the Cockcroft-Gault formula)
6. ­ Anticipated life expectancy of less than 3 months
7. ­ Participation in another interventional clinical trial evaluating a health product or any randomized clinical trial
8. ­ Absence of affiliation to National French social security system
9. ­ Under legal protection measure (tutorship or curatorship) and patient deprived of freedom

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary outcome is the rate of good functional outcome (independent ambulation) at 3 months defined as a modified Rankin scale (mRS) score of 0-3. mRS scores will be determined by certified raters unaware of the treatment arm or baseline characteristics of the individual patient by in person interview or, if not possible, by telephone.

Secondary endpoints 4

1. Clinical outcomes - early neurological improvement, defined as a ≥ 8-points decrease of the NIHSS score or a NIHSS score ≤ 1 at day 1 - 3-month functional independence (mRS score ≤ 2) - distribution of 3-month mRS scores - one-year independent ambulation (mRS score ≤ 3) - one-year functional independence (mRS score ≤ 2)
2. Radiological outcomes - successful, excellent and complete recanalisation rates defined as an extended Treatment In Cerebral Ischemia (eTICI) scores of 2b50/2b67/2c/3, 2c/3 and 3 respectively on the first angiographic run, after the first pass and at the end of the procedure - mean change in infarct volume from baseline at day 1, defined as: (day 1 volume) – (baseline volume
3. Safety outcomes - early neurological worsening defined as a ≥ 4-point increase on the NIHSS score within 24 hours due to the stroke itself - intracranial hemorrhage (ICH) according to the Heidelberg Bleeding Classification - symptomatic ICH, scored according to the Heidelberg Bleeding Classification - 3-month and 1-year mortality - adverse events - serious adverse events
4. Incremental cost-utility ratio

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Gaspard GERSCHENFELD

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Gaspard GERSCHENFELD

Locations

1 EU/EEA country · 36 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 15 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