Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke: The MARVEL Randomized Clinical Trial

Abstract

Importance: It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy.

Objective: To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO.

Design, setting, and participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.

Interventions: Eligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy.

Main outcomes and measures: The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours.

Results: Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo.

Conclusions and relevance: Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.

Trial registration: ChiCTR.org.cn Identifier: ChiCTR2100051729.

Figure 1.. Patients in a Study of the Effect of Intravenous Methylprednisolone vs Placebo as Adjunct to Endovascular Thrombectomy

ASPECTS indicates Alberta Stroke Program Early CT Score; ICA, intracranial carotid artery; M1, the first segment of middle cerebral artery; and M2, the second segment of the middle cerebral artery. ^aASPECTS ranges from 0 to 10, with 1 point subtracted for early ischemic change in each defined region on the noncontrast computed tomographic scan. ^bRandomization was stratified by participating center. ^ceFigure 1 in Supplement 3 provides detailed explanations of protocol violations.

Figure 2.. Distribution of Global Disability at 90 Days Based on the Modified Rankin Scale Score

Shown are the distribution of the modified Rankin Scale score among patients in the methylprednisolone and placebo groups. Scores range from 0 to 6, with 0 indicating no symptoms; 1, no clinically significant disability; 2, slight disability; 3, moderate disability; 4, moderately severe disability; 5, severe disability; and 6, death. Numbers indicate rounded proportions. Data of 7 patients who withdrew consent were not included. Data of 4 patients in the methylprednisolone group and 3 patients in the placebo group with missing data were not included. The sum was not 100 because of rounding. Treatment with methylprednisolone was associated with an adjusted generalized odds ratio of 1.10 (95% CI, 0.96-1.25; P = .17) for the distribution of the modified Rankin Scale at 90 days.

Figure 3.. Heterogeneity of Treatment Effect for Less Disability Among Prespecified Subgroups

Shown is the subgroup analysis based on the adjusted generalized odds ratio (genOR), indicating the odds that the trial patients assigned to the methylprednisolone group would have better functional recovery at 90 days than patients assigned to receive placebo. The widths of the confidence intervals were not adjusted for multiple comparisons, and the reported confidence intervals should not be used for hypothesis testing. The age, National Institutes of Health Stroke Scale (NIHSS) score, and time from stroke onset to randomization were divided at median of the whole population as prespecified in the statistical analysis plan. The sizes of the boxes in the plot correspond to the number of patients in each subgroup. The arrow indicates that the 95% CI was beyond the scale. The prespecified subgroup analysis by status of hemorrhage was not represented here because they are postrandomization characteristics. ASPECTS indicates Alberta Stroke Program Early Computed Tomography Score; ICA, intracranial carotid artery; M1, the first segment of middle cerebral artery; M2, the second segment of the middle cerebral artery; and mRS, modified Rankin Scale. ^aScores on the NIHSS range from 0 to 42, with higher scores indicating worse neurologic deficits. ^bScores on the mRS of functional disability range from 0 (no symptoms) to 6 (death). ^cASPECTS range from 0 to 10, with lower values indicating larger infarction; data were not available for 6 patients. ^dData for reperfusion were not available for 2 patients. ^eThe strict COVID-19 control period (before January 8, 2023) subgroup in the COVID-19 category included all patients who completed their primary outcome assessment before January 8, 2023, which marks the beginning of the downgrade in COVID-19 management measures. In the strict COVID-19 control period, no patients had COVID-19 infection. The COVID-19 peak period (after January 8, 2023) included patients who completed the primary outcome assessment after January 8, 2023.