Reperfusion with P2Y12 inhibitors in addition to mechanical thrombectomy for perfusion imaging selected acute stroke patients : a multicentric randomized controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondation A De Rothschild

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

1 Aug 2024 → ongoing

Decision date (initial)

2024-08-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-516163-88-00

EudraCT number

2020-005451-20

ClinicalTrials.gov

NCT04667078

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Evaluate the efficacy of P2Y12 inhibitor (cangrelor) in addition to MT and BMM compared to MT and BMM alone on functional outcome at 3 months, in AIS patients selected on perfusion imaging between 0 and 24h after stroke onset.

Secondary objectives 4

1. Evaluate the efficacy of cangrelor in addition to MT and BMM compared to MT and BMM on functional outcome at 3 months (“shift analysis”)
2. Evaluate the efficacy of cangrelor in addition to MT and BMM compared to MT and BMM on reperfusion results at the end of treatment.
3. Evaluate the efficacy of cangrelor in addition to MT and BMM compared to MT and BMM on early neurological improvement at 24 hours
4. Evaluate the efficacy of cangrelor in addition to MT and BMM compared to MT and BMM on stroke volume at 24-36 hours.

Conditions and MedDRA coding

Acute ischemic stroke

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age 18 or older
2. Anterior circulation intracanial large artery occlusion isolated (Intracranial ICA and/or MCA) proved on CTA or MRA
3. Symptoms onset < 24h at imaging
4. Indication for MT and fulfillment of the following brain imaging criteria : 1. Perfusion imaging: An initial infarct volume (ischemic core on DWI or CTP calculated by the RAPID software) of less than 70 ml, a ratio between the critically hypoperfused lesion volume (calculated by RAPID with a TMax>6s) and initial infarct volume of 1.8 or more, and an absolute difference between those 2 volumes of 15 ml or more. OR (if perfusion imaging not available or uninterpretable) : 2. CORE CLINICAL MISMATCH: Core calculated on DWI by RAPID, <25 mL if NIHSS 6-20 and <50 mL if NIHSS>20 OR (if RAPID results are not considered reliable by the clinician) : 3. CORE CLINICAL MISMATCH according to the clinician evaluation
5. Pre-stroke mRS ≤ 2
6. NIHSS ≥ 6

Exclusion criteria 17

1. Contraindication to MT
2. Patient over 80 years old with >10 microbleeds on pre-treatment MRI
3. Pre-existing dependency with mRS ≥3
4. Known tandem ICA-MCA occlusions requiring stenting
5. ASPECT<6 on NCCT or DWI-MRI
6. Known hypersensitivity to cangrelor or to any of the excipients (mannitol, sorbitol)
7. History of previous intracranial hemorrhage
8. Evidence of active bleeding or acute trauma (fracture) on examination
9. Recent surgery with a significant risk of bleeding
10. VKA oral anticoagulation with INR >1.7
11. Curative heparin or direct oral anticoagulants (DOACs) in previous 48 hours with specific DOAC dosage ≥50 ng/ml and abnormal thrombin time for patients on dabigatran or abnormal specific anti-Xa activity for patients on apixaban, edoxaban, or rivaroxaban
12. Platelet count <100 000/ mm3
13. Woman of childbearing age without a pregnancy test or with a positive serum pregnancy test
14. Patient benefiting from a legal protection
15. Non-membership of a national insurance scheme
16. Opposition of the patient or (in case of inclusion as a matter of urgency) of the trustworthy person
17. Participation in another study regarding AIS care interfering with this study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Favorable functional outcome defined by a modified Rankin Scale (mRS) score ≤ 2 at 3 months.

Secondary endpoints 7

1. mRS shift analysis at 3 months.
2. a. Rate of near or complete reperfusion at end of treatment defined by modified treatment in cerebral infarction (mTICI) score 2c or 3. b. Rate of successful reperfusion at end of treatment defined by modified treatment in cerebral infarction (mTICI) score of 2b or 2c or 3.
3. Change in NIHSS from baseline to 24 hours after treatment.
4. Volume assessed by the ASPECTS score (Assessment in Acute Stroke Alberta Stroke Program Early CT) at 24-36 hours.
5. Rate of all-cause mortality at 3 months.
6. Rate of symptomatic intracranial hemorrhage according the Heidelberg definition associated to at least 4 points worsening in NIHSS at 24-36h after treatment.
7. Rate of any intracranial hemorrhage according the Heidelberg definition at 24-36h after treatment.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondation A De Rothschild

Sponsor organisation

Fondation A De Rothschild

Address

29 Rue Manin

City

Paris

Postcode

75019

Country

France

Scientific contact point

Organisation

Fondation A De Rothschild

Contact name

Clinical Research Department

Public contact point

Organisation

Fondation A De Rothschild

Contact name

Clinical Research Department

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 10 files

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

Application history

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