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SWIFT DIRECT

Thrombectomy Alone Versus Intravenous Alteplase Plus Thrombectomy in Patients with Stroke: A Randomized Controlled Non-Inferiority Trial

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Year of Publication: 2021

Authors: Prof. Urs Fischer MD, Johannes Kaesmacher MD, Daniel Strbian MD, ..., Prof. Jeffrey L. Saver MD and Prof. Jan Gralla MD on behalf of the SWIFT DIRECT Collaborators

Journal: The Lancet

Citation: Lancet 2022; 400(10346): 104-115.

Link: https://boris.unibe.ch/171267/8/Fischer_Lancet_2022_AAM.pdf

PDF: https://boris.unibe.ch/171267/8/Fischer_Lancet_2022_AAM.pdf

Clinical Question

To determine whether stent-retriever thrombectomy alone is non-inferior to intravenous alteplase (IVT) plus stent-retriever thrombectomy for achieving good functional outcome in patients with acute ischemic stroke due to a large vessel occlusion in the anterior circulation.

Bottom Line

In this trial, thrombectomy alone was not shown to be non-inferior to standard care (intravenous alteplase plus thrombectomy) for achieving functional independence at 90 days. Furthermore, thrombectomy alone resulted in a lower rate of successful reperfusion. These results do not support omitting intravenous alteplase before thrombectomy in eligible patients.

Major Points

  • SWIFT DIRECT was a multicenter, randomized, open-label, non-inferiority trial involving 408 patients in Europe and Canada.
  • Patients with large vessel occlusion stroke eligible for both IVT and thrombectomy were randomized 1:1 to thrombectomy alone or IVT plus thrombectomy.
  • The primary outcome was functional independence, defined as a modified Rankin Scale (mRS) score of 0-2 at 90 days, with a non-inferiority margin of a -12% risk difference.
  • The primary outcome was achieved by 57% of patients in the thrombectomy-alone group and 65% in the IVT-plus-thrombectomy group.
  • Non-inferiority was not met, as the lower limit of the one-sided 95% CI for the adjusted risk difference was -15.1%, crossing the prespecified -12% margin.
  • Successful reperfusion (eTICI 2b50-3) was significantly less common in the thrombectomy-alone group compared to the combined therapy group (91% vs. 96%; P=0.047).
  • Safety outcomes, including symptomatic intracranial hemorrhage, were similar between the groups.

Design

Study Type: Multicenter, randomized, open-label, blinded-outcome, non-inferiority trial

Randomization: 1

Blinding: The trial was open-label for treatment, but the primary outcome assessment was performed by personnel blinded to the treatment allocation.

Enrollment Period: November 2017 to May 2021

Follow-up Duration: 90 days

Centers: 48

Countries: Europe, Canada

Sample Size: 408

Analysis: The primary outcome was assessed for non-inferiority in the intention-to-treat population using the one-sided lower 95% confidence limit of the Mantel-Haenszel risk difference, with a non-inferiority margin of -12%.

Inclusion Criteria

  • CTA- or MRA-confirmed occlusion of the intracranial internal carotid artery, the M1 segment of the middle cerebral artery, or both
  • Eligible to receive intravenous alteplase within 4.5 hours from the time last seen well
  • Could undergo thrombectomy within 75 minutes of randomization
  • NIHSS score of ≥5 and ≤30
  • Alberta Stroke Program Early CT Score (ASPECTS) of ≥4

Exclusion Criteria

  • Advanced dementia or significant preexisting disabilities

Baseline Characteristics

CharacteristicControlActive
GroupIntravenous alteplase plus thrombectomy (N=207)Thrombectomy alone (N=201)
Median age - yr (IQR)72 (65, 81)73 (64, 81)
Female sex - no. (%)104 (50%)105 (52%)
Median NIHSS score (IQR)17 (12, 20)17 (13, 20)
Median ASPECTS - (IQR)8 (7, 9)8 (7, 9)

Arms

FieldControlThrombectomy alone
InterventionStandard of care: Intravenous alteplase (0.9 mg/kg, max 90 mg) administered as soon as possible, followed by thrombectomy with a Solitaire stent-retriever device.Thrombectomy with a Solitaire stent-retriever device initiated as soon as possible, without preceding intravenous alteplase.
DurationSingle interventionSingle intervention

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Functional independence, defined as a score of 0-2 on the modified Rankin scale (mRS) at 90 days.Primary65% (135/207)57% (114/201)Non-inferiority not met
Successful reperfusion (final eTICI 2b50-3)Secondary96% (199/207)91% (182/201)Risk difference -5.1% (95% CI, -10.2 to 0.0%)0.047
Mortality at 90 daysSecondary9% (17/207)11% (22/201)Risk difference 2.3% (95% CI, -3.2 to 7.8%)0.41
Symptomatic intracranial hemorrhage (global definition)Adverse3% (7/202)2% (5/201)Risk difference -1.0% (95% CI, -4.8 to 2.7%)0.77

Subgroup Analysis

A hypothesis-generating analysis suggested a differential effect by age, with a significant detriment to thrombectomy alone in patients <70 years old, but this should be interpreted with caution.

Criticisms

  • Most patients were treated with a specific type of stent-retriever (Solitaire), so results may not be generalizable to other thrombectomy devices.
  • The study used a broad non-inferiority margin of -12%.
  • The per-protocol analysis was limited to 83% of patients.
  • The population was confined to patients directly admitted to comprehensive stroke centers, and results are not transferable to drip-and-ship models.
  • Approximately half of the patients were randomized after admission MRI, which may limit the generalizability of the data.

Funding

Medtronic and University Hospital Bern.

Based on: SWIFT DIRECT (The Lancet, 2021)

Authors: Prof. Urs Fischer MD, Johannes Kaesmacher MD, Daniel Strbian MD, ..., Prof. Jeffrey L. Saver MD and Prof. Jan Gralla MD on behalf of the SWIFT DIRECT Collaborators

Citation: Lancet 2022; 400(10346): 104-115.

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