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MR RESCUE

A Trial of Imaging Selection and Endovascular Treatment for Ischemic Stroke

Year of Publication: 2013

Authors: Chelsea S. Kidwell, Reza Jahan, Jeffrey Gornbein, et al.

Journal: New England Journal of Medicine

Citation: Kidwell CS, Jahan R, Gornbein J, et al. A Trial of Imaging Selection and Endovascular Treatment for Ischemic Stroke. N Engl J Med. 2013;368:914–923.

Link: https://www.nejm.org/doi/full/10.1056/NEJMoa1212793

PDF: https://www.nejm.org/doi/pdf/10.1056/NEJMoa1212793

Clinical Question

Does neuroimaging-based penumbral selection identify patients with acute ischemic stroke who differentially benefit from endovascular therapy?

Bottom Line

Endovascular therapy with first-generation devices did not show benefit over standard care in patients with large-vessel anterior-circulation ischemic stroke within 8 hours, and a favorable penumbral imaging pattern did not identify patients who differentially benefited from embolectomy.

        Major Points
        MR RESCUE assessed whether imaging-defined penumbra could identify patients who differentially benefit from endovascular therapy.
Randomized patients within 8 hours of symptom onset to mechanical embolectomy (Merci Retriever or Penumbra System) vs standard medical care.
Used multimodal MRI or CT to stratify patients as having favorable penumbral vs nonpenumbral pattern before randomization.
No significant interaction between imaging pattern and treatment on 90-day mRS (P=0.14).
Trial failed to demonstrate benefit of endovascular therapy overall (mean 90-day mRS 3.9 vs 3.9, P=0.99), possibly due to first-generation devices and a low rate of substantial revascularization.
Laid groundwork for better patient selection methods in later trials (e.g., DEFUSE 3, DAWN).

      

Design

Study Type: Phase 2b, multicenter, randomized, controlled, open-label (blinded outcome) trial with imaging stratification

Randomization: 1

Blinding: Open-label with blinded outcome assessment

Enrollment Period: 2004 – 2011

Follow-up Duration: 90 days

Centers: 22

Countries: North America

Sample Size: 118

Analysis: Nonparametric two-way analysis of variance using permutational methods, with prespecified interaction test between penumbral pattern and treatment assignment on 90-day mRS

Inclusion Criteria

Acute ischemic stroke due to anterior circulation large vessel occlusion (ICA or MCA)
Age 18–85
NIHSS 6–29
Randomization within 8 hours of symptom onset
Pretreatment multimodal CT or MRI of the brain

Exclusion Criteria

Per Figure 1, 9 of 127 randomized patients were excluded from the primary analyses: 5 did not have a target lesion on vessel imaging, 2 did not have post–t-PA vessel imaging, and 2 had failed perfusion imaging. Additional prespecified exclusion criteria are not enumerated in the primary paper (see Supplementary Appendix).

Baseline Characteristics

Characteristic	Control	Active
Age (mean)	67.1	64.2
Female (%)	50%	53%
NIHSS (median)	16 (penumbral) / 20.5 (nonpenumbral); overall all-patient median 17 (IQR 13–21) — arm-aggregate median not reported in paper	16 (penumbral) / 19 (nonpenumbral); overall all-patient median 17 (IQR 13–21) — arm-aggregate median not reported in paper
Favorable penumbral pattern (%)	63%	53%
IV tPA received (%)	30%	44%

Arms

Field	Endovascular Therapy	Control
Intervention	Mechanical embolectomy using Merci Retriever or Penumbra System (intraarterial t-PA up to 14 mg allowed as rescue within 6 hours)	Supportive care and IV tPA if eligible; no endovascular therapy
Duration	Single procedure within 8 hours of onset; 90-day follow-up	90-day follow-up

Outcomes

Outcome	Type	Control	Intervention	P-value
90-day modified Rankin Scale (mRS) distribution; primary test was interaction between penumbral pattern and treatment assignment	Primary	Mean mRS 3.9	Mean mRS 3.9	0.99 (overall treatment comparison); interaction P=0.14
Revascularization (TICI 2a–3) in embolectomy group	Secondary	NA	67%
Mortality at 90 days (paper reports 4 subgroups: Embolectomy-Penumbral 6/34 [18%], Standard-Penumbral 7/34 [21%], Embolectomy-Nonpenumbral 6/30 [20%], Standard-Nonpenumbral 6/20 [30%])	Secondary	24% (13/54)	19% (12/64)	0.75 (4-group overall comparison per Table 2 footnote; no arm-aggregate P reported)
Symptomatic intracerebral hemorrhage (paper reports 4 subgroups: 3 [9%], 2 [6%], 0, 0)	Secondary	4% (2/54)	5% (3/64)	0.24 (4-group overall comparison per Table 2 footnote; no arm-aggregate P reported)
Good outcome (mRS 0–2) at 90 days (paper reports 4 subgroups: 7 [21%], 9 [26%], 5 [17%], 2 [10%])	Secondary	20% (11/54)	19% (12/64)	0.48 (4-group overall comparison per Table 2 footnote; no arm-aggregate P reported)
Symptomatic ICH	Adverse	4% (2/54)	5% (3/64)	0.24 (4-group overall comparison per Table 2 footnote; no arm-aggregate P reported)
Mortality	Adverse	24% (13/54)	19% (12/64)	0.75 (4-group overall comparison per Table 2 footnote; no arm-aggregate P reported)
Asymptomatic ICH	Adverse	48% (26/54)	66% (42/64)	0.04 (4-group overall comparison per Table 2 footnote; no arm-aggregate P reported)

Subgroup Analysis

No significant interaction between imaging pattern and treatment (P=0.14). Favorable penumbral: mean mRS 3.9 (embolectomy) vs 3.4 (standard care), P=0.23. Nonpenumbral: 4.0 vs 4.4, P=0.32.

Criticisms

Small sample size and underpowered
First-generation endovascular devices (Merci, Penumbra) with low rate of substantial revascularization (paper distinguishes reperfusion 37–57% from revascularization/TICI 2a–3 67–93% across subgroups)
Long enrollment period (2004–2011) limited applicability to modern practice
Long time from imaging to embolectomy (groin puncture >6 hours from symptom onset)
Heterogeneity of imaging modalities (both MRI and CT)
Real-time penumbral processing succeeded in only 58% of cases

Funding

National Institute of Neurological Disorders and Stroke (NINDS) grant P50 NS044378; Concentric Medical provided devices until August 2007

Based on: MR RESCUE (New England Journal of Medicine, 2013)

Authors: Chelsea S. Kidwell, Reza Jahan, Jeffrey Gornbein, et al.

Citation: Kidwell CS, Jahan R, Gornbein J, et al. A Trial of Imaging Selection and Endovascular Treatment for Ischemic Stroke. N Engl J Med. 2013;368:914–923.

Content summarized and formatted by NeuroTrials.ai.

MR RESCUE

(2013)

Objective

To evaluate whether neuroimaging selection based on penumbral patterns identifies patients who benefit from endovascular therapy for acute ischemic stroke.

Study Summary

• This phase 2b trial found no significant benefit of mechanical embolectomy over standard care, regardless of whether patients had favorable or non-favorable penumbral imaging patterns..

Intervention

Mechanical embolectomy using Merci Retriever or Penumbra system vs. standard medical care. Neuroimaging used to classify patients by penumbral pattern.

Inclusion Criteria

Ischemic stroke within 8 hours, anterior circulation occlusion, NIHSS 6–29, with MRI or CT-based penumbral imaging before randomization.

Study Design

Arms: Mechanical Embolectomy vs. Standard Care

Patients per Arm: Embolectomy: 64, Standard care: 54

Outcome

• No significant difference in 90-day mRS scores: both groups mean score 3.9. <br>• No interaction between imaging pattern and treatment. <br>• Embolectomy did not improve outcomes..

Bottom Line

Major Points

MR RESCUE assessed whether imaging-defined penumbra could identify patients who differentially benefit from endovascular therapy.
Randomized patients within 8 hours of symptom onset to mechanical embolectomy (Merci Retriever or Penumbra System) vs standard medical care.
Used multimodal MRI or CT to stratify patients as having favorable penumbral vs nonpenumbral pattern before randomization.
No significant interaction between imaging pattern and treatment on 90-day mRS (P=0.14).
Trial failed to demonstrate benefit of endovascular therapy overall (mean 90-day mRS 3.9 vs 3.9, P=0.99), possibly due to first-generation devices and a low rate of substantial revascularization.
Laid groundwork for better patient selection methods in later trials (e.g., DEFUSE 3, DAWN).

Study Design

Study Type: Phase 2b, multicenter, randomized, controlled, open-label (blinded outcome) trial with imaging stratification
Randomization: Yes
Blinding: Open-label with blinded outcome assessment
Sample Size: 118
Follow-up: 90 days
Centers: 22
Countries: North America

Primary Outcome

Definition: 90-day modified Rankin Scale (mRS) distribution; primary test was interaction between penumbral pattern and treatment assignment

Control	Intervention	HR/OR	P-value
Mean mRS 3.9	Mean mRS 3.9	-	0.99 (overall treatment comparison); interaction P=0.14

Limitations & Criticisms

Small sample size and underpowered
First-generation endovascular devices (Merci, Penumbra) with low rate of substantial revascularization (paper distinguishes reperfusion 37–57% from revascularization/TICI 2a–3 67–93% across subgroups)
Long enrollment period (2004–2011) limited applicability to modern practice
Long time from imaging to embolectomy (groin puncture >6 hours from symptom onset)
Heterogeneity of imaging modalities (both MRI and CT)
Real-time penumbral processing succeeded in only 58% of cases

Citation

Kidwell CS, Jahan R, Gornbein J, et al. A Trial of Imaging Selection and Endovascular Treatment for Ischemic Stroke. N Engl J Med. 2013;368:914–923.

View Original Publication →

MR RESCUE

A Trial of Imaging Selection and Endovascular Treatment for Ischemic Stroke

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Baseline Characteristics

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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