Elsevier

The Lancet

Volume 393, Issue 10175, 9–15 March 2019, Pages 998-1008
The Lancet

Articles
Aspiration thrombectomy versus stent retriever thrombectomy as first-line approach for large vessel occlusion (COMPASS): a multicentre, randomised, open label, blinded outcome, non-inferiority trial

https://doi.org/10.1016/S0140-6736(19)30297-1Get rights and content

Summary

Background

Stent retriever thrombectomy of large-vessel occlusion results in better outcomes than medical therapy alone. Alternative thrombectomy strategies, particularly a direct aspiration as first pass technique, while promising, have not been rigorously assessed for clinical efficacy in randomised trials. We designed COMPASS to assess whether patients treated with aspiration as first pass have non-inferior functional outcomes to those treated with a stent retriever as first line.

Methods

We did a multicentre, randomised, open label, blinded outcome, core lab adjudicated non-inferiority trial at 15 sites (ten hospitals and four specialty clinics in the USA and one hospital in Canada). Eligible participants were patients presenting with acute ischaemic stroke from anterior circulation large-vessel occlusion within 6 h of onset and an Alberta Stroke Program Early CT Score of greater than 6. We randomly assigned participants (1:1) via a central web-based system without stratification to either direct aspiration first pass or stent retriever first line thrombectomy. Those assessing primary outcomes via clinical examinations were masked to group assignment as they were not involved in the procedures. Physicians were allowed to use adjunctive technology as was consistent with their standard of care. The null hypothesis for this study was that patients treated with aspiration as first pass achieve inferior outcomes compared with those treated with a stent retriever first line approach. The primary outcome was non-inferiority of clinical functional outcome at 90 days as measured by the percentage of patients achieving a modified Rankin Scale score of 0–2, analysed by intent to treat; non-inferiority was established with a margin of 0·15. All randomly assigned patients were included in the safety analyses. This trial is registered at ClinicalTrials.gov, number: NCT02466893.

Findings

Between June 1, 2015, and July 5, 2017, we assigned 270 patients to treatment: 134 to aspiration first pass and 136 to stent retriever first line. A modified Rankin score of 0–2 at 90 days was achieved by 69 patients (52%; 95% CI 43·8–60·3) in the aspiration group and 67 patients (50%; 41·6–57·4) in the stent retriever group, showing that aspiration as first pass was non-inferior to stent retriever first line (pnon-inferiority=0·0014). Intracranial haemorrhage occurred in 48 (36%) of 134 in the aspiration first pass group, and 46 (34%) of 135 in the stent retriever first line group. All-cause mortality at 3 months occurred in 30 patients (22%) in both groups.

Interpretation

A direct aspiration as first pass thrombectomy conferred non-inferior functional outcome at 90 days compared with stent retriever first line thrombectomy. This study supports the use of direct aspiration as an alternative to stent retriever as first-line therapy for stroke thrombectomy.

Funding

Penumbra.

Introduction

Multiple randomised trials1, 2, 3, 4, 5, 6, 7 have established thrombectomy as the standard of care for appropriate patients with large vessel occlusion.8, 9, 10 These trials predominantly used stent retriever devices to do a thrombectomy. It is unclear whether the benefit observed in these trials would persist if an alternative method of thrombectomy was used. As a result, established stroke guidelines specifically recommend the use of stent retrievers to the exclusion of other thrombectomy techniques.8, 10 A direct aspiration first pass technique is an aspiration-first approach to performing thrombectomy. This technique uses a large-bore catheter to aspirate the thrombus without initially using a stent retriever. If aspiration alone is not successful, then the large-bore catheter serves as a conduit to alternatively use a stent retriever or other means to do the thrombectomy. Findings from initial single-arm studies have suggested the direct aspiration first pass approach has promising safety and clinical efficacy, with potential improvements in time and cost compared with using a stent retriever first line approach.11, 12 The technical comparability of these two approaches was also suggested when the ASTER trial,13 a prospective randomised trial designed to show superior angiographic outcomes with direct aspiration first pass technique compared with a stent retriever as a first line approach, failed in its primary outcome, but had similar clinical results in each arm.13

Research in context

Evidence before this study

We searched MEDLINE for studies published between Jan 1, 2014, and Jan 1, 2019, using any combination of two of the following search terms with no language restrictions: “stroke”, “thrombectomy”, or “randomized trial”. This search yielded ten randomised trials providing evidence that thrombectomy was superior to medical therapy for treatment of emergent large-vessel stroke. However, all but one study were primarily based upon stent retriever technology; the tenth study, THERAPY, failed to meet its primary endpoint. ASTER is the only reported trial that used aspiration thrombectomy as a first pass approach versus stent retriever as a first line approach, and it failed to meet its primary endpoint of angiographic superiority for aspiration thrombectomy as first pass. As a result, it is unclear whether the benefit of thrombectomy is unique to a single approach–stent retriever as first line or whether alternate approaches to thrombectomy would also confer a clinical benefit. Whether stent retrievers are a necessary component for successful thrombectomy is hotly debated internationally, as most clearly evidenced by the variable language used across multiple society clinical guidelines.

Added value of this study

COMPASS was a North American, prospective, multicentre, masked assessor, randomised trial assessing the non-inferiority of aspiration thrombectomy as first pass versus stent retriever as first line for large vessel occlusion. COMPASS directly addressed whether stent retrievers are necessary for successful thrombectomy, with strongly positive results.

Implications of all the available evidence

COMPASS, with the supportive but non-clinically focused ASTER results, provides level 1 data that an aspiration thrombectomy as first pass approach is non-inferior to a stent retriever as first line approach for the treatment of selected patients with acute large vessel ischaemic stroke. This finding will be of broad interest to all stroke physicians and might directly affect current stroke treatment guideline recommendations. Furthermore, these data have the potential to substantially reduce the cost of thrombectomy procedures worldwide.

To date there have not been any randomised trials designed specifically to assess clinical outcome with the aspiration-first approach compared with established stent retriever technology. Furthermore, there are no randomised data available on the cost differential between the two approaches, a major benefit claimed by proponents of the direct aspiration first pass technique. We designed a randomised controlled trial (COMPASS) to assess whether patients treated with the aspiration first pass approach have non-inferior functional outcomes compared with those treated with a stent retriever first line approach, and to secondarily assess for technical, clinical, and cost superiority of the aspiration-first approach.

Section snippets

Study design and participants

We did a prospective, multicentre, randomised, open-label, blinded outcome, core lab adjudicated, concurrent control, non-inferiority trial at 15 sites (ten hospitals and four specialty clinics in the USA and one hospital in Canada). Sites were chosen with consideration of their preferred thrombectomy method to avoid bias based on pre-existing operator philosophy. Centres were required to submit details of their 20 most recent thrombectomy cases to ensure practitioner familiarity with both

Results

Between June 1, 2015, and July 5, 2017, we enrolled 270 patients and randomly assigned 134 to direct aspiration first pass thrombectomy and 136 to stent retriever first line thrombectomy (figure 1). Of the 15 trial sites, one was activated but did not enrol (University of Miami Hospital). Six sites enrolled 25 or more patients each, and ten sites enrolled more than ten patients each. Of the 15 sites that were activated, six sites had a bias towards the aspiration first pass approach and six had

Discussion

The results showed that of patients presenting within 6 h of onset of an anterior circulation acute large vessel occlusion and an ASPECTS greater than 6, those who were treated with a direct aspiration as first pass thrombectomy approach had non-inferior functional outcome compared with those treated with a stent retriever as first line thrombectomy approach. These data confirm the non-inferiority of aspiration as first pass compared with stent retriever first line with regard to the primary

Data sharing

The study protocol, statistical plan, and de-indentified individual data that underlie the results in this article will be available for investigators whose proposed data use has been approved by a review committee within the next 24 months. Please email [email protected].

References (21)

  • S Bracard et al.

    Mechanical thrombectomy after intravenous alteplase versus alteplase alone after stroke (THRACE): a randomised controlled trial

    Lancet Neurol

    (2016)
  • OA Berkhemer et al.

    A randomized trial of intraarterial treatment for acute ischemic stroke

    N Engl J Med

    (2015)
  • M Goyal et al.

    Randomized assessment of rapid endovascular treatment of ischemic stroke

    N Engl J Med

    (2015)
  • TG Jovin et al.

    Thrombectomy within 8 hours after symptom onset in ischemic stroke

    N Engl J Med

    (2015)
  • BCV Campbell et al.

    Endovascular therapy for ischemic stroke with perfusion-imaging selection

    N Engl J Med

    (2015)
  • J Mocco et al.

    Aspiration thrombectomy after intravenous alteplase versus intravenous alteplase alone

    Stroke

    (2016)
  • JL Saver et al.

    Stent-retriever thrombectomy after intravenous t-PA vs t-PA alone in stroke

    N Engl J Med

    (2015)
  • WJ Powers et al.

    2018 Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association

    Stroke

    (2018)
  • KA Blackham et al.

    Endovascular therapy of acute ischemic stroke: report of the Standards of Practice Committee of the Society of NeuroInterventional Surgery

    J Neurointerv Surg

    (2012)
  • SD Lavine et al.

    Training guidelines for endovascular stroke intervention: an international multi-society consensus document

    Interv Neurol

    (2016)
There are more references available in the full text version of this article.

Cited by (340)

View all citing articles on Scopus
View full text