Clinical trial NCT06071091: Permanent Intracranial Stenting for Acute Ischemic Stroke Related to a Refractory Large Vessel Occlusion
Official title: Comparison of Permanent Intracranial Stenting Versus no Stenting in Stroke Secondary to Refractory Acute Proximal Vascular Occlusion: a Multicenter Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Acute Ischemic Stroke
Keywords: Brain
Intracranial
Ischemia
Stroke
Mechanical Thrombectomy
Intracranial Occlusion
Refractory Occlusion
Interventional
Angioplasty
Stenting
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2023-10-06
Enrollment: 346
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Clot extraction failure during mechanical thrombectomy is a major concern in the management of acute ischemic stroke related to large vessel occlusions. Indeed, it can occur in up to 10 to 30% of cases and, therefore, is associated with a very poor prognosis. These refractory occlusions frequently occur when an underlying intracranial atherosclerotic disease is present. Thus, one of the most promising rescue technique consists of placing a permanent intracranial stent, under dual antiplatelet therapy over the target refractory occlusion. This strategy is well studied in coronary occlusions where the atheroscotic mechanism is highly prevalent. However, as the ischemiated brain is at much higher risk of hemorrhagic complications, such strategy entails a greater risk. This raises the question of whether such risk is worth the reward of obtaining reperfusion. The investigators designed this randomized study in order to evaluate whether a strategy combining rescue pemanent intracranial stenting with the best medical treatment is superior to the best medical treatment alone in acute refractory large vessel occlusions.

Detailed description: These past recent years, mechanichal thrombectomy has become the standard treatment for acute ischemic strokes due to large vessel occlusions. Mechanical thrombectomy failure occurs in about 10 to 30% of cases with disastrous consequences for these patients. Indeed, reperfusion failures are associated with 30.5% mortality rates and only 21% of all patients are able to achieve functional independence at 3 months.

In order to treat these refractory large vessel occlusions many techniques and devices have been developped. Rescue Intracranial Stenting (RIS) is the most studied technique and the most promising one. However, RIS requires strong antithrombotic medications to ensure stent patency, which may increase the risk of hemorrhagic complications.

The investigators recently performed a meta-analysis of observational data, that showed that RIS in refractory large vessel occlusions allowed significant improvements in functional outcome at 3 months. The rate of good functional outcome at 3 months went from 21% in the control group (no RIS) to 43% in the RIS group. Mortality was also significantly reduced from 30.5% (control group) to 18.8% in the RIS group. Furthermore, RIS did not increase the rate of symptomatic intracranial hemorrhage.

Of course, this meta-analysis is only based on observational data and needs to be confirmed in a randomized trial to bring the highest level of evidence.

Refractory large vessel occlusions are commonly caused by an underlying intracranial atherosclerotic plaque. Since the SAMMPRIS trial, most of the indications for the endovascular treatment of intracranial atherosclerotic stenoses have been removed. Nevertheless, there are subsets of patients who actually benefit from intracranial stenting such as patients with refractory large vessel occlusions or patients with hemodynamically significant stenoses. As such, the PISTAR trial could be a way of validating intracranial stenting in this indication.

All patients admitted for a mechanical thrombectomy will be screened before the procedure. If the patient fulfills the preoperative elligibility criteria, she/he will be informed of the possibility of being included in case of a refractory occlusion. If the patients' clinical state does not allow her/him to give informed consent, she/he can still be included using an emergency consent procedure. Consents to pursue the study will be sought as soon as possible, from the patient or her/his trusted relative.

If the patient meets all remaining elligibility criteria during the mechanical thrombectomy in particular if the occlusion is considered as refractory, she/he can be included and randomized.

Randomization will be performed using a minimization procedure based on the recruiting center, the administration of IV thrombolysis and the location of the occlusion (anterior versus posterior circulation). The randomzation will be centralized using an online e-crf platform.

The patient can be randomized in one of the two following arms

* Intervention arm : RIS + best medical treatment In this arm, a dedicated antithrombotic protocol will be initiated before the deployment of the stent. The choice of antithrombotics and the need to perform additional endovascular manœuvres such as balloon angioplasty will be left at the operator's discretion. A standard protocol for antithrombotics is proposed.
* Control arm : best medical treatment with no additional thrombectomy passes In this arm, the procedure is stopped and a last control angiogram is performed to confirm the absence of reperfusion. Any additional medical treatment is allowed.

Follow up visits will be performed immediately after the procedure (V0), at 24hrs (V1), 72hs (V2) and 1 month (V3). The end-research visit will be performed at 3 months (+/- 15 days) and a remote safety visit will be performed at 6 months.

Eligibility criteria: Inclusion Criteria:

* Age\>18 years
* Acute ischemic stroke secondary to an occlusion of the internal carotid artery termination OR the 1st or 2nd segment of the middle cerebral artery OR the basilar artery and/or the 4th segment of the vertebral artery radiologically proven (CT Angiography or angio-MRI)
* Patient within the authorised timeframe for a MT, according to the AHA/ASA 2019 grade I recommendations
* Refractory intracranial large vessel occlusion defined as :

Persistent arterial occlusion (mTICI 0 or I) after a minimum of 3 mechanical thrombectomy passes using direct aspiration or a stent retriever OR Early arterial reocclusion (\<10 minutes) after at least one pass OR Underlying stenosis (estimated between 70 and 99%)

* ASPECT Score for CT or DWI-ASPECTS for MRI or pc(-DWI)- ASPECTS (posterior circulation) ≥ 5
* Independent patient before stroke (mRS 0-2)
* Patient's or her/his trusted relative's consent or emergency procedure consent

Exclusion Criteria:

* Proximal intracranial vascular occlusion not confirmed on angiography
* Intracranial bleeding \<3 months or intracranial bleeding during TM procedure prior to inclusion
* Contraindication to a dual antiplatelet therapy
* Mechanical thrombectomy procedure requiring carotid or vertebral arterial access by direct puncture
* Proof of significant ischemic lesions in a vascular territory not affected by the occlusion
* Proven allergy to iodinated contrast material
* Patient known for severe renal impairment with creatinine clearance \< 30ml/min
* Pregnant or breastfeeding women
* Tandem occlusion (defined as the association of an intracranial occlusion to a cervical steno-occlusive lesion on the same arterial axis that needs additional endovascular manœuvers for the cervical lesion)
* Major comorbidities that could hinder the improvement or the follow up of the patient or the benefit of the intervention
* Unaffiliation to the French Social Security system
* Patient under juridic protection
* Patient participating in another interventional trial

Primary outcomes:
measure: Rate of independent patients
timeFrame: 3 months
Secondary outcomes:
measure: Mortality
timeFrame: 6 months
measure: Excellent functional outcome
timeFrame: 3 months
measure: modified Rankin Scale (mRS)
timeFrame: 3 months
measure: Successful reperfusion
timeFrame: End of procedure (up to 4 hours)
measure: Excellent reperfusion
timeFrame: End of procedure (up to 4 hours)
measure: Symptomatic ischemic recurrence
timeFrame: 3 months
measure: Rate of patients requiring a new mechanical thrombectomy
timeFrame: 3 months
measure: Neurologic recovery
timeFrame: 24 hours
measure: Neurologic recovery
timeFrame: 72 hours
measure: Periprocedural time (time between arterial puncture and successful reperfusion (if obtained))
timeFrame: End of procedure (up to 4 hours)
measure: Periprocedural time (Time between onset of symptoms (or "last seen normal") and successful reperfusion (if obtained))
timeFrame: End of procedure (up to 4 hours)
measure: Periprocedural time (Time between randomization and successful reperfusion (if obtained))
timeFrame: End of procedure (up to 4 hours)
measure: Procedure duration
timeFrame: End of procedure (up to 4 hours)
measure: Intracranial hemorrhagic complications
timeFrame: 6 months
measure: Distribution of intracranial hemorrhagic complications
timeFrame: 6 months
measure: Serious extracranial hemorrhagic complications
timeFrame: 6 months
measure: All procedural complications
timeFrame: Up to 6 months
measure: Vascular perforation
timeFrame: End of procedure (up to 4 hours)
measure: Dissection
timeFrame: End of procedure (up to 4 hours)
measure: Embolism in a territory not previously affected by the ischemia
timeFrame: End of procedure (up to 4 hours)
measure: Serious complication on the arterial access
timeFrame: 6 months
measure: Vascular reocclusion
timeFrame: 24 hours
measure: Adverse events
timeFrame: 6 months
measure: Serious adverse events
timeFrame: 6 months
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens
city: Bordeaux
country: France
facility: CHU Bordeaux (Pellegrin Hospital)
city: Créteil
country: France
facility: Henri-Mondor Hospital (APHP)
city: Créteil
country: France
facility: Henri-Mondor Hospital (APHP)
city: Le Kremlin-Bicêtre
country: France
facility: Bicêtre Hospital (AP-HP)
city: Le Kremlin-Bicêtre
country: France
facility: Bicêtre Hospital (APHP)
city: Lille
country: France
facility: CHU Lille (Roger Salengro Hospital)
city: Montpellier
country: France
facility: CHU Montpellier - Gui de Chauliac
city: Nancy
country: France
facility: CHRU de Nancy
city: Paris
country: France
facility: Lariboisière Hospital (APHP)
city: Paris
country: France
facility: APHP • Assistance Publique des Hôpitaux de Paris, Pitié-Salpêtrière hospital
city: Poitiers
country: France
facility: CHU Poitiers
city: Suresnes
country: France
facility: Foch Hospital
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Kevin PREMAT, MD
role: PRINCIPAL_INVESTIGATOR
References: