Permanent Intracranial Stenting for Acute Ischemic Stroke Related to a Refractory Large Vessel Occlusion

Acute Ischemic Stroke Clinical Trial

— PISTAR  

Official title:

Comparison of Permanent Intracranial Stenting Versus no Stenting in Stroke Secondary to Refractory Acute Proximal Vascular Occlusion: a Multicenter Randomized Controlled Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06071091
• Other study ID #: APHP210091
• Secondary ID: 2022-A00570-43
• Status: Active, not recruiting
• Phase: N/A
• Start date: November 8, 2023
• Est. completion date: August 1, 2027

Study information

• Verified date: January 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 346
• Est. completion date: August 1, 2027
• Est. primary completion date: February 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Device:
• Intracranial stenting
In order to promote the efficacy of the stent to reopen the target vessel, there are two requirments prior stenting: First, balloon angioplasty can be performed at operators' discretion based on angiographic findings. Second, a dual antiplatelet therapy protocol is considered essential to maintain stent patency, and therefore should be introduced before stent implantation whenever possible. Permanent Intracranial can then be performed according to the standard technique: An autoexpandable intracranial stent (Neuroform Atlas 4x24mm) is deployed though a dedicated microcatheter over the target refractory occlusion The only stent system allowed is the Neuroform Atlas 4x24mm (Stryker Neurovascular) The anti-thrombotic drugs used, their route of administration, the choice of navigation equipment are left to the discretion of the team in charge of the patient. A standardized anti-thrombotic protocol will be proposed as an indication.

Other:
• Optimal medical care, without additional endovascular procedures
The control group represents the standard therapeutic strategy for refractory vascular occlusions, which consists of stopping the procedure without performing any additional mechanical thrombectomy attempts. In this group, the procedure will be stopped after randomization and a control seriography will be performed to confirm the persistent nature of the intracranial occlusion. The patient will benefit from the best medical care available, which may include any medical treatment including a dual anti-platelet therapy if the therapeutic team deems it necessary (Standard medical care may also include (non-exhaustive list): Nursing Nursing care Symptomatic treatments: analgesics for example Systematic clinical monitoring and control imaging if necessary Rehabilitation if necessary)

Locations

Country	Name	City	State
France	CHU Amiens	Amiens
France	CHU Bordeaux (Pellegrin Hospital)	Bordeaux
France	Henri-Mondor Hospital (APHP)	Créteil
France	Henri-Mondor Hospital (APHP)	Créteil
France	Bicêtre Hospital (AP-HP)	Le Kremlin-Bicêtre
France	Bicêtre Hospital (APHP)	Le Kremlin-Bicêtre
France	CHU Lille (Roger Salengro Hospital)	Lille
France	CHU Montpellier - Gui de Chauliac	Montpellier
France	CHRU de Nancy	Nancy
France	APHP • Assistance Publique des Hôpitaux de Paris, Pitié-Salpêtrière hospital	Paris
France	Lariboisière Hospital (APHP)	Paris
France	CHU Poitiers	Poitiers
France	Foch Hospital	Suresnes

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of independent patients	Rate of independent patients at 3 months, defined as a modified Rankin Scale (mRS) 0-2, evaluated by a trained health professional, blinded to the randomization arm.; Min=0 ; Max=6 (lower is better)	3 months
Secondary	Mortality	Mortality rate at 6 months	6 months
Secondary	Excellent functional outcome	Rate of excellent functional prognosis defined as a modified Rankin Scale (mRS) score of 0-1 at 3 months Min=0 ; Max=6 (lower is better)	3 months
Secondary	modified Rankin Scale (mRS)	Distribution of mRS scores at 3 months Min=0 ; Max=6 (lower is better)	3 months
Secondary	Successful reperfusion	Successful reperfusion rate (Score modified Thrombolysis In Cerebral Infarction [mTICI] =IIb) Min=0 ; Max=3 (higher is better)	End of procedure (up to 4 hours)
Secondary	Excellent reperfusion	Excellent reperfusion rate (defined as modified Thrombolysis In Cerebral Infarction [mTICI] score =IIc) Min=0 ; Max=3 (higher is better)	End of procedure (up to 4 hours)
Secondary	Symptomatic ischemic recurrence	Rate of symptomatic ischemic recurrence (=4 points of National Institutes of Health Stroke Scale (NIHSS) compared to the lowest NIHSS score during management) certified by imaging within 3 months.; Min=0 ; Max=42 (lower is better)	3 months
Secondary	Rate of patients requiring a new mechanical thrombectomy	Rate of patients requiring a new mechanical thrombectomy within the group of patients with symtomatic ischemic recurrence	3 months
Secondary	Neurologic recovery	Neurologic recovery at 24 hours, according to the National Institutes of Health Stroke Scale (NIHSS) score as compared to initial NIHSS score Min=0 ; Max=42 (lower is better)	24 hours
Secondary	Neurologic recovery	Neurologic recovery at 72 hours, according to the National Institutes of Health Stroke Scale (NIHSS) score as compared to initial NIHSS score Min=0 ; Max=42 (lower is better)	72 hours
Secondary	Periprocedural time (time between arterial puncture and successful reperfusion (if obtained))	Time between arterial puncture and successful reperfusion (if obtained)	End of procedure (up to 4 hours)
Secondary	Periprocedural time (Time between onset of symptoms (or "last seen normal") and successful reperfusion (if obtained))	Time between onset of symptoms (or "last seen normal") and successful reperfusion (if obtained)	End of procedure (up to 4 hours)
Secondary	Periprocedural time (Time between randomization and successful reperfusion (if obtained))	Time between randomization and successful reperfusion (if obtained)	End of procedure (up to 4 hours)
Secondary	Procedure duration	Time between arterial puncture and arterial closure	End of procedure (up to 4 hours)
Secondary	Intracranial hemorrhagic complications	Rate of symptomatic intracranial haemorrhage at 6 months defined as any intracranial haemorrhage responsible for neurological deterioration (=4 NIHSS points compared to the lowest NIHSS score during management)	6 months
Secondary	Distribution of intracranial hemorrhagic complications	Distribution of intracranial hemorrhagic complications according to the Heidelberg classification	6 months
Secondary	Serious extracranial hemorrhagic complications	Rate of serious extra-cranial hemorrhagic complications at 6 months, defined as any extra-cranial bleeding complication requiring re-hospitalization and/or surgery and/or blood transfusion	6 months
Secondary	All procedural complications	Rate of all procedural complications, including vascular perforation, dissection, embolism in a territory not previously affected by the ischemia and serious complications on the arterial access (as defined below)	Up to 6 months
Secondary	Vascular perforation	Rate of vascular perforation during the procedure	End of procedure (up to 4 hours)
Secondary	Dissection	Rate of dissection during the procedure	End of procedure (up to 4 hours)
Secondary	Embolism in a territory not previously affected by the ischemia	Rate of embolism in a territory not previously affected by the ischemia, during the procedure	End of procedure (up to 4 hours)
Secondary	Serious complication on the arterial access	Rate of serious complications on the arterial access, defined as any superficial hematoma with deglobulisation [loss of 2 Hb points on the NFS] and/or requiring a transfusion, retroperitoneal hematoma with or without deglobulisation, arterial pseudo-aneurysm at the puncture site requiring surgical treatment, femoral artery occlusion and/or acute limb ischemia, puncture site abscess.	6 months
Secondary	Vascular reocclusion	Rate of vascular reocclusion on 24-hour imaging	24 hours
Secondary	Adverse events	Rate of adverse events at 6 months	6 months
Secondary	Serious adverse events	Rate of serious adverse events at 6 months	6 months