DAWN and DEFUSE 3 trial

DAWN and DEFUSE 3 trial from Sun Yai-Cheng

DAWN trial

The first RCT evidence of a group identifiable by clinical and imaging criteria who derive benefit from mechanical thrombectomy after 6 hours

General Inclusion Criteria

• Age ≥ 18;
• failed or contraindicated for IV t-PA
• NIHSS ≥10
• Pre-stroke –mRS 0-1
• Time last seen well to randomization: 6-24 hrs

Imaging Inclusion criteria

• < 1/3 MCA territory by CT or MRI
• ICA and/or MCA-M1 occlusion
• Clinical Imaging Mismatch
  
  • group A: age ≥ 80 y/o, NIHSS ≥ 10 and core infarct size < 20 ml
  • group B: age < 80 y/o, NIHSS ≥ 10 and core infarct size < 30 ml
  • group C: age < 80 y/o, NIHSS ≥ 20 and core infarct size < 50 ml 

Exclusion Criteria

• similar to IV alteplase exclusions

End Point Results

 Co-1 end points:

90-day disability assessed by utility weighted mRS: 5.5 +/- 3.8 vs 3.4 +/- 3.1
Adjusted Difference 2.0, 95% CI, 1.1-3.0
Posterior probability of superiority >0.999

mRS 0-2 at 90 d: 49% vs 13%
Adjusted Difference 33%, 95% CI, 21%-44%
posterior probability of superiority >0.999

Safety end point:

Mortality at 90 d: 19% vs 18%, P=1.00
sICH: 6% vs 3%, P=0.50

Subgroups by time:

90-day mRS 0-2

6-12 hrs: 55.1% vs 20.0%,posterior probability of superiority >0.99
12-24 hrs: 43.1% vs 7.4%, posterior probability of superiority >0.99

Stopped early at first interim analysis

DEFUSE 3 trial

Expands criteria to identify patients who benefit from mechanical thrombectomy
after 6 hours

Inclusion Criteria

• Age 18-90 years
• NIHSSS ≥ 6
• Femoral puncture within 6 -16 hours of stroke onset/last known well
• Premorbid mRS2 ≤2
• ICA or M1 occlusion by MRA or CTA AND Target Mismatch Profile on CT perfusion or MRI (ischemic core volume < 70 ml, mismatch ratio > 1.8 and mismatch volume > 15 ml)

Exclusion Criteria

similar to IV alteplase exclusions, including:

• BP > 185/110
• treated with tPA >4.5 hours after time last known well
• treated with tPA 3-4.5 hours after last known well AND any of the following: age >80, current anticoagulant use, history of diabetes AND prior stroke
• NIHSS >25
• ASPECT score < 6
• Significant mass effect with midline shift
• acute symptomatic arterial occlusions in more than one vascular territory

End Point Results

mRS 0-2 at 90d: 44.6% % vs 16.7%, Relative risk: 2.67; 95% CI 1.60-4.48; P< 0.0001
Mortality at 90 d: 14% vs 26%; P= 0.053
sICH: 6.5% vs 4.4%; P= 0.75

Stopped early at first interim analysis

Reference

Diffusion-weighted imaging or computerized tomography perfusion assessment with clinical mismatch in the triage of wake up and late presenting strokes undergoing neurointervention with Trevo (DAWN) trial methods
Int J Stroke. 2017 Aug;12(6):641-652.

Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct
N Engl J Med. 2018 Jan 4;378(1):11-21.

A multicenter randomized controlled trial of endovascular therapy following imaging evaluation for ischemic stroke (DEFUSE 3)
Int J Stroke. 2017 Oct;12(8):896-905.

Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging
N Engl J Med. 2018 Feb 22;378(8):708-718.

Related Articles: 2018 Stroke Guidelines