Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03192332
Recruitment Status : Recruiting
First Posted : June 20, 2017
Last Update Posted : July 29, 2020
Sponsor:
Collaborator:
Medtronic
Information provided by (Responsible Party):
University Hospital Inselspital, Berne

Tracking Information
First Submitted Date  ICMJE June 12, 2017
First Posted Date  ICMJE June 20, 2017
Last Update Posted Date July 29, 2020
Actual Study Start Date  ICMJE November 29, 2017
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 15, 2017)
Score in modified Rankin Scale (mRS) [ Time Frame: 90 days after randomization ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 15, 2017)
  • Mortality [ Time Frame: 90 days after randomization ]
  • Modified Rankin Scale (mRS) shift analysis [ Time Frame: day 0 and 90 days after randomization ]
  • National Institute of Health Score Scale (NIHSS) [ Time Frame: day 0 and day 1 after randomization ]
  • Thrombolysis in Cerebral Infarction (TICI) scale [ Time Frame: day 0 and day 1 after randomization ]
  • Serious adverse events [ Time Frame: day 0 until 90 days after randomization ]
  • Intracranial hemorrhage [ Time Frame: day 1 after randomization ]
  • Quality of life assessed by questionnaire [ Time Frame: 90 days after randomization ]
  • Overall costs incurred during hospitalisation [ Time Frame: 90 days after randomization ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bridging Thrombolysis Versus Direct Mechanical Thrombectomy in Acute Ischemic Stroke
Official Title  ICMJE Solitaire™ With the Intention For Thrombectomy Plus Intravenous t-PA Versus DIRECT Solitaire™ Stent-retriever Thrombectomy in Acute Anterior Circulation Stroke
Brief Summary

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Prospective, randomized, open label, blinded endpoint (PROBE)
Masking: Single (Outcomes Assessor)
Masking Description:
Assessment of the primary outcome will be performed by an independent and blinded person.
Primary Purpose: Treatment
Condition  ICMJE Ischemic Stroke
Intervention  ICMJE
  • Device: Stent-retriever thrombectomy with revascularization device of the Solitaire™ type
    Mechanical thrombectomy with a stent-retriever revascularization device
  • Drug: Intravenous thrombolysis with recombinant tissue-type plasminogen activator (IV t-PA)
    Bridging thrombolysis (IV t-PA plus mechanical thrombectomy) according to current European and North American stroke guidelines.
Study Arms  ICMJE
  • Experimental: Direct mechanical thrombectomy
    Treatment with direct mechanical thrombectomy with a commercially available stent-retriever revascularization device of the Solitaire™ type.
    Intervention: Device: Stent-retriever thrombectomy with revascularization device of the Solitaire™ type
  • Active Comparator: Combined intravenous thrombolysis and mechanical thrombectomy
    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.
    Interventions:
    • Device: Stent-retriever thrombectomy with revascularization device of the Solitaire™ type
    • Drug: Intravenous thrombolysis with recombinant tissue-type plasminogen activator (IV t-PA)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 15, 2017)
404
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2023
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Informed consent as documented by signature
  2. Age ≥ 18
  3. Clinical signs consistent with an acute ischemic stroke
  4. Neurological deficit with a NIHSS of ≥ 5 and < 30 (deficits judged to be clearly disabling at presentation)
  5. Patient is eligible for intravenous thrombolysis
  6. Patient is eligible for endovascular treatment
  7. Randomization no later than 4 hours 15 minutes after stroke symptom onset and initiation of IV t-PA must be started within 4 hours 30 minutes of stroke symptoms onset (onset time is measured from the time when the subject was last seen well)
  8. Occlusion (TICI 0-1) of the intracranial internal carotid artery (ICA), the M1 segment of the middle cerebral artery (MCA), or both confirmed by CT or MR angiography, accessible for MT
  9. Core-infarct volume of Alberta Stroke Program Early CT Score (ASPECTS) greater than or equal to 4 (≥ 4) based on baseline CT or MR imaging (MRI) (a region has to have diffusion abnormality in 20% or more of its volume to be considered MR-ASPECTS positive)

Exclusion Criteria:

  1. Acute intracranial hemorrhage
  2. Any contraindication for IV t-PA
  3. Pre-treatment with IV t-PA
  4. In-hospital stroke
  5. Pregnancy or lactating women. A negative pregnancy test before randomization is required for all women with child-bearing potential.
  6. Known (serious) sensitivity to radiographic contrast agents, nickel, titanium metals, or their alloys
  7. Known current participation in a clinical trial (investigational drug or medical device)
  8. Renal insufficiency as defined by a serum creatinine > 2.0 mg/dl (or 176.8 µmol/l) or glomerular filtration rate (GFR) < 30 mL/min or requirement for hemodialysis or peritoneal dialysis
  9. Severe comorbid condition with life expectancy less than 90 days at baseline
  10. Known advanced dementia or significant pre-stroke disability (mRS score of ≥2)
  11. Foreseeable difficulties in follow-up due to geographic reasons (e.g. patients living abroad)
  12. Comorbid disease or condition that would confound the neurological and functional evaluations or compromise survival or ability to complete follow-up assessments.
  13. Subject currently uses or has a recent history of illicit drug(s) or abuses alcohol (defined as regular or daily consumption of more than four alcoholic drinks per day).
  14. Known history of arterial tortuosity, pre-existing stent, other arterial disease and/or known disease at the femoral access site that would prevent the device from reaching the target vessel and/or preclude safe recovery after MT
  15. Radiological confirmed evidence of mass effect or intracranial tumor (except small meningioma)
  16. Radiological confirmed evidence of cerebral vasculitis
  17. CTA or MRA evidence of carotid artery dissection
  18. Evidence of additional distal intracranial vessel occlusion in another territory (i.e. A2 segment of anterior cerebral artery or M3, M4 segment of MCA) on initial NCCT/MRI or CTA/MRA
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Patricia Plattner, MSc +41 31 632 39 70 patricia.plattner@insel.ch
Listed Location Countries  ICMJE Austria,   Canada,   Finland,   France,   Germany,   Spain,   Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03192332
Other Study ID Numbers  ICMJE 2017-00974
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Hospital Inselspital, Berne
Study Sponsor  ICMJE University Hospital Inselspital, Berne
Collaborators  ICMJE Medtronic
Investigators  ICMJE
Principal Investigator: Urs Fischer, Prof. Dr. Dept. of Neurology, Inselspital Bern
Principal Investigator: Jan Gralla, Prof. Dr. Dept. of Neuroradiology, Inselspital Bern
PRS Account University Hospital Inselspital, Berne
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP