Bridging Thrombolysis Versus Direct Mechanical Thrombectomy in Acute Ischemic Stroke "SWIFT DIRECT"

Recruiting

Phase N/A Results N/A

Trial Description

Intravenous thrombolysis with recombinant tissue-type plasminogen activator (IV t-PA) has been the only proven therapy for acute ischemic stroke (AIS) for almost 20 years. Whether IV t-PA prior to endovascular clot retrieval is beneficial for AIS patients with a proximal vessel occlusion in the anterior circulation has currently become a matter of debate and is a relevant unanswered question in clinical practice.
The main objective is to determine whether subjects experiencing an AIS due to large intracranial vessel occlusion in the anterior circulation will have non-inferior functional outcome at 90 days when treated with direct mechanical thrombectomy (MT) compared to subjects treated with combined IV t-PA and MT.
The secondary objectives are to study causes of mortality, dependency and quality of life in these AIS patients.

Detailed Description

Intravenous thrombolysis with recombinant tissue-type plasminogen activator (IV t-PA) has been the only proven therapy for acute ischemic stroke (AIS) for almost 20 years. Since December 2014 a new era in acute stroke treatment has begun: randomized controlled studies have consistently shown that endovascular clot retrieval in addition to best medical treatment (± IV t-PA) improves outcome in acute anterior circulation stroke patients with proximal vessel occlusion compared to best medical treatment alone. Whether pre-treatment with IV t-PA prior to endovascular clot retrieval is beneficial has now become a matter of debate. A pooled analysis of 5 RCTs (MR CLEAN, SWIFT-PRIME, EXTEND IA, ESCAPE and REVASCAT) suggested that the treatment effect size of MT does not differ between patients receiving intravenous thrombolysis (IVT) and those treated with MT alone (p interaction: 0.4311). Besides post-hoc RCT analyses, there are a myriad of observational studies reporting on rates of successful reperfusion and functional outcome stratified according to IV t-PA pretreatment status. There is evidence that reperfusion rates after IV t-PA in patients with occlusions of the internal carotid artery and the main stem of the middle cerebral artery are low, but may reach more than 80% after mechanical thrombectomy (MT). Therefore the most important factor for vessel recanalization, which is linked with favorable outcome, is MT.
No randomized controlled trial has ever assessed whether direct MT in patients with AIS is equally effective as MT in combination with IV t-PA (bridging thrombolysis). In a patient-level pooled analysis of five randomized controlled studies (HERMES collaboration) similar rates of functional independence and mortality at 90 days were observed between patients who received IV t-PA+MT and those who received direct MT. However, patients in the direct MT group had contraindications for IV t-PA. Two larger studies based on registries compared the outcome of patients after bridging thrombolysis with direct MT in patients eligible for IV t-PA. In both studies, the outcome of patients after bridging thrombolysis and direct MT was similar. For these reasons the investigators hypothesize that immediate and direct MT is not inferior and might even be superior to bridging thrombolysis in patients directly referred to a stroke center with rapid access to endovascular procedures.
In this trial all commercially available stent-retriever revascularization devices manufactured by Medtronic (e.g. Solitaire™) will be used as tool for direct MT. The investigators aim to provide conclusive information on the efficacy and safety of direct MT, in comparison with bridging thrombolysis.
If direct MT in patients with AIS would not be inferior to bridging thrombolysis, the organization of acute stroke management would change essentially. Direct MT would then be the therapy of choice in stroke centers with endovascular facilities. Furthermore, this trial could have an impact on healthcare guidelines and costs. However, this trial does not address the question, whether patients arriving in stroke units with no endovascular facilities should be pre-treated with IV t-PA or whether they should directly be referred to stroke centers with endovascular facilities.

Conditions

Interventions

  • Stent-retriever thrombectomy with revascularization device of the Solitaire™ type Device
    Intervention Desc: Mechanical thrombectomy with a stent-retriever revascularization device
    ARM 1: Kind: Experimental
    Label: Direct mechanical thrombectomy
    Description: Treatment with direct mechanical thrombectomy with a commercially available stent-retriever revascularization device of the Solitaire™ type.
    ARM 2: Kind: Experimental
    Label: Combined intravenous thrombolysis and mechanical thrombectomy
    Description: Treatment with intravenous thrombolysis with recombinant tissue-type plasminogen activator (IV t-PA) followed by mechanical thrombectomy with a commercially available stent-retriever revascularization device of the Solitaire™ type.
  • Intravenous thrombolysis with recombinant tissue-type plasminogen activator (IV t-PA) Drug
    Intervention Desc: Bridging thrombolysis (IV t-PA plus mechanical thrombectomy) according to current European and North American stroke guidelines.
    ARM 1: Kind: Experimental
    Label: Combined intravenous thrombolysis and mechanical thrombectomy
    Description: Treatment with intravenous thrombolysis with recombinant tissue-type plasminogen activator (IV t-PA) followed by mechanical thrombectomy with a commercially available stent-retriever revascularization device of the Solitaire™ type.

Outcomes

Type Measure Time Frame Safety Issue
Primary Score in modified Rankin Scale (mRS) 90 days after randomization
Secondary Mortality 90 days after randomization
Secondary Modified Rankin Scale (mRS) shift analysis day 0 and 90 days after randomization
Secondary National Institute of Health Score Scale (NIHSS) day 0 and day 1 after randomization
Secondary Thrombolysis in Cerebral Infarction (TICI) scale day 0 and day 1 after randomization
Secondary Serious adverse events day 0 until 90 days after randomization
Secondary Intracranial hemorrhage day 1 after randomization
Secondary Quality of life assessed by questionnaire 90 days after randomization
Secondary Overall costs incurred during hospitalisation 90 days after randomization

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