Endovascular Acute Stroke Intervention Trial - the EASI Trial "EASI"

Recruiting

Phase N/A Results N/A

Trial Description

Stroke constitutes the primary cause of acquired disability in adults and the second cause of dementia following Alzheimer disease. It has been shown that patients with a moderate to severe clinical score have occlusion of brain large vessels, resulting in a worse clinical outcome. Many studies have demonstrated that early recanalization after IV rtPA is more restricted, the larger and more proximal the artery. Several systems for mechanical intracranial arterial thrombectomy of large trunks have recently been proposed and are now available. Potential advantages of these mechanical systems on chemical thrombolysis are speed (a few minutes versus 1 hour) and absence of thrombolytic injection.
The objective of the EASI trial is thus to:
- To validate intra-arterial thrombectomy use during the acute phase of cerebral stroke in patients treated with IV thrombolysis or in patients for whom thrombolysis is contra-indicated.
- To determine whether a combined approach, standard treatment plus thrombectomy, is superior to standard treatment alone within 5 h of the appearance of symptoms, in patients with occlusion of proximal cerebral arteries following moderate to severe stroke (NIHSS larger than or equal to 8), evaluated at 3 months.
The design is a randomized, controlled multicentric trial, with a parallel comparison between standard and combined (standard plus thrombectomy) treatment.
480 patients fulfilling eligibility criteria will be sufficient to demonstrate the primary hypothesis of a 15% difference in number of subjects with a favorable mRS (less than or equal to 2) at 3 months, with the assumption of a 25% efficacy for IV thrombolytic treatment at 3 months.
IV thrombolysis is carried out according to standard practice. Mechanical thrombectomy is carried out with already approved devices, according to the manufacturer's instructions, following a diagnostic cerebral angiography.
The primary efficacy endpoint is clinical: favorable mRS (less than or equal to 2) at 3 months.
The primary safety endpoint is rate of death at 3 months and rate of symptomatic hemorrhage at 24 hours.
If the primary hypothesis is validated, expected benefits of this study is a higher rate of autonomy for stroke patients with all the attendant consequences: reduction in hospital stays, and a faster return to the activities of daily life.

Detailed Description

Background Stroke constitutes the primary cause of acquired disability in adults and the second cause of dementia following Alzheimer disease. The burden of disease may be substantial since 25% of the victims of stroke are younger than 65 years. Standard treatment is IV rtPA thrombolysis, within 3-4.5 hours of first signs. It has been shown that patients with a moderate to severe clinical score (NIHSS more than 10) have occlusion of proximal large vessels, resulting in a more adverse clinical outcome. Many studies have demonstrated that early recanalization after IV rtPA is more restricted, the larger and more proximal the artery. Recanalization of large arteries occurs more frequently and earlier (leading to better prognosis) with arterial than with venous access. Biochemical arterial treatment appears thus of greater efficacy in terms of recanalization of large vessels, but more inconvenient with respect to setup delays. Several systems for mechanical intracranial arterial thrombectomy of large trunks have recently been proposed and are now available. Results of short case series and prospective multicentric non randomized studies appear favorable. The thrombus obstructing the artery is reached by endovascular means and mechanically removed with the result that orthograde blood flow is re-established in the cerebral territory involved in the ischemia. Potential advantages of these mechanical systems on chemical thrombolysis are speed (a few minutes versus 1 hour) and absence of thrombolytic injection. Mechanical thrombolysis should thus lead to better results than injection of an arterial thrombolytic agent, as well as increase the time window for treatment. In addition, hemorrhagic complications should be reduced.
Objectives
In situations where IV rtPA thrombolysis is not optimal, that is in presumed embolic occlusions of large intracranial arterial trunks (terminal carotid, initial segment of the MCA, distal third of the basilar trunk) with a moderate to severe clinical state (NIHSS greater or equal to 8) and in situations when IV rtPA may be contra-indicated:
- To validate intra-arterial thrombectomy use during the acute phase of cerebral stroke in patients treated with IV thrombolysis or in patients for whom thrombolysis is contra-indicated.
- To determine whether a combined approach, standard treatment plus thrombectomy, is superior to standard treatment alone within 5 h of the appearance of symptoms, in patients with occlusion of proximal cerebral arteries following moderate to severe stroke (greater or equal to 8), evaluated at 3 months.
Design EASI is a randomized, controlled multicentric trial, with a parallel comparison between standard and combined (standard plus thrombectomy) treatment. All adults presenting less than 5 hours after the beginning of symptoms with an NIHSS greater or equal to 8 discordant with imaging data are eligible. Occlusion site, when available, includes intracranial carotid artery, M1 segment of middle cerebral and basilar artery.
480 patients fulfilling eligibility criteria will be sufficient to demonstrate the primary hypothesis of a 15% difference in number of subjects with a favorable mRS (greater than 2) at 3 months, with the assumption of a 25% efficacy (mRS less or equal to 2) for IV thrombolytic treatment at 3 months.
Randomization may take place any time following admission, including during IV thrombolysis. The choice of early randomization, without knowledge of the clinical or angiographic results of IV thrombolysis fulfils several objectives: allow timely delivery of a proven treatment; prevent unnecessary exposure to angiography risks; set up thrombectomy as fast as possible for a maximal efficacy.
IV thrombolysis is carried out according to standard practice. Mechanical thrombectomy is carried out with already approved devices, according to the manufacturer's instructions, following a diagnostic cerebral angiography.
Follow-up includes brain imaging and the mRS at 3 months.
Endpoint measures include:
- Clinical endpoints as measured by the neurologist, and include the NIHSS at baseline and the mRS at 3 months.
- Safety data: complications, death at 3 months, hemorrhage according to 24 hours CT scan.
The primary efficacy endpoint is clinical: favorable mRS (less than or equal to 2) at 3 months.
The primary safety endpoint is rate of death at 3 months and rate of symptomatic hemorrhage at 24 hours.
Secondary efficacy endpoints include:
- Comparison of ASPECTS score between baseline and 24 hours CT scans
- In thrombectomy group, blood flow in treated territory as measured by a TICI reperfusion score of 2 or 3 at end of treatment.
Secondary safety endpoints include
- Rate of hemorrhage on 24 hours CT scan
- Frequency and severity of complications of standard treatment
- Frequency and severity of arterial complications in thrombectomy group
- Frequency and severity of complications at puncture site in thrombectomy group

Conditions

Interventions

  • Mechanical Thrombectomy (Merci Retriever)Device
    Other Names: Penumbra system; TREVO; Solitaire
    Intervention Desc: Mechanical thrombectomy using any already approved stent-retriever device
    ARM 1: Kind: Experimental
    Label: Mechanical thrombectomy
    Description: Endovascular mechanical thrombectomy with stent-retrievers
  • Stent-retriever Device
    Other Names: any already approved brand
    Intervention Desc: Mechanical thrombectomy using any already approved stent-retriever device
    ARM 1: Kind: Experimental
    Label: Mechanical thrombectomy (stent-retriever)
    Description: Endovascular mechanical thrombectomy with stent-retrievers
  • R-tPA (recombinant tissue Plasminogen Activator) Drug
    Other Names: any brand name
    Intervention Desc: Intravenous r-tPA infusion or any other medical management option
    ARM 1: Kind: Experimental
    Label: Medical
    Description: Best standard treatment: intravenous r-tPA or any other medical management
  • Best standard treatment Drug
    Other Names: Medical management
    Intervention Desc: Intravenous r-tPA infusion or any other medical management option
    ARM 1: Kind: Experimental
    Label: Best standard treatment
    Description: intravenous r-tPA or any other medical management

Trial Design

  • Allocation: Randomized
  • Masking: Open Label
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary clinical (efficacy): favorable modified Rankin Score (less than or equal to 2) 3 months Yes
Primary Rate of symptomatic intracranial hemorrhage 24 hours Yes
Secondary Infarct evolution 24 hours No
Secondary Angiographic outcome in patients allocated to mechanical thrombectomy 2 hours No
Secondary Frequency and Severity of complications 3 months Yes
Secondary Rate of intracranial hemorrhage 24 hours Yes

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