PDF: MR CLEAN-NO IV
(2021)Objective
To determine whether direct mechanical thrombectomy is non-inferior to intravenous alteplase followed by thrombectomy in patients with anterior circulation LVO.
Study Summary
Intervention
Direct EVT versus standard bridging therapy with IV alteplase followed by EVT.
Inclusion Criteria
Adults ≥18 years, anterior circulation LVO (intracranial ICA, M1, proximal M2), eligible for both IV alteplase and EVT, presenting directly to EVT-capable centers within 4.5 hours of stroke onset.
Study Design
Arms: Direct thrombectomy vs. IV alteplase + thrombectomy
Patients per Arm: Direct: 273, Bridging: 266
Outcome
Bottom Line
In European patients with acute ischemic stroke due to large vessel occlusion, endovascular treatment (EVT) alone was neither superior nor noninferior to standard care with intravenous alteplase followed by EVT with regard to disability outcome at 90 days. The incidence of symptomatic intracerebral hemorrhage and mortality was similar between the two groups.
Major Points
- This was an open-label, multicenter, randomized trial involving 539 patients in Europe with acute ischemic stroke eligible for both intravenous alteplase and endovascular treatment (EVT).
- Patients were randomized 1:1 to receive EVT alone or the standard of care (intravenous alteplase followed by EVT).
- The primary outcome was the functional score on the modified Rankin scale (mRS) at 90 days.
- The trial found no significant difference in the distribution of mRS scores between the two groups (adjusted common odds ratio, 0.84; 95% CI, 0.62 to 1.15), failing to show superiority or noninferiority for EVT alone.
- Mortality at 90 days was 20.5% with EVT alone and 15.8% with alteplase plus EVT.
- Symptomatic intracerebral hemorrhage occurred in 5.9% of the EVT-alone group and 5.3% of the alteplase-plus-EVT group.
Study Design
- Study Type
- Investigator-initiated, international, multicenter, prospective, randomized, open-label trial with blinded end-point assessment
- Randomization
- Yes
- Blinding
- Open-label for treatment, but primary end-point assessment was performed by trained research nurses who were unaware of trial-group assignments.
- Sample Size
- 539
- Follow-up
- 90 days
- Centers
- 20
- Countries
- Netherlands, Belgium, France
Primary Outcome
Definition: Functional outcome on the modified Rankin scale (mRS) at 90 days, analyzed for a shift in the distribution of scores.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Median mRS 2 (IQR, 2 to 5) | Median mRS 3 (IQR, 2 to 5) | - (0.62 to 1.15) | 0.28 |
Limitations & Criticisms
- The trial results apply only to patients presenting directly to a center capable of providing EVT and may not be generalizable to patients who are transferred from another hospital.
- The trial had an open-label design, which may have influenced postprocedural patient care.
- There were small baseline imbalances between the groups, with more prognostically unfavorable characteristics (atrial fibrillation, age, ICA occlusion) in the EVT-alone group, which may have affected the results in favor of the standard care group.
- The use of deferred consent made a pure intention-to-treat analysis difficult, though it only affected eight patients.
Citation
N Engl J Med 2021;385:1833-44