Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: One-Year Follow-up.

BACKGROUND AND OBJECTIVES: Declines in stroke admission, intravenous thrombolysis, and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the impact of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), intravenous thrombolysis (IVT), and mechanical thrombectomy over a one-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020). METHODS: We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, intravenous thrombolysis treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. RESULTS: There were 148,895 stroke admissions in the one-year immediately before compared to 138,453 admissions during the one-year pandemic, representing a 7% decline (95% confidence interval [95% CI 7.1, 6.9]; p<0.0001). ICH volumes declined from 29,585 to 28,156 (4.8%, [5.1, 4.6]; p<0.0001) and IVT volume from 24,584 to 23,077 (6.1%, [6.4, 5.8]; p<0.0001). Larger declines were observed at high volume compared to low volume centers (all p<0.0001). There was no significant change in mechanical thrombectomy volumes (0.7%, [0.6,0.9]; p=0.49). Stroke was diagnosed in 1.3% [1.31,1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82,2.97], 5,656/195,539) of all stroke hospitalizations. DISCUSSION: There was a global decline and shift to lower volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared to the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year. TRIAL REGISTRATION INFORMATION: This study is registered under NCT04934020.

Tranexamic acid for intracerebral haemorrhage within 2 hours of onset: protocol of a phase II randomised placebo-controlled double-blind multicentre trial.

RATIONALE: Haematoma growth is common early after intracerebral haemorrhage (ICH), and is a key determinant of outcome. Tranexamic acid, a widely available antifibrinolytic agent with an excellent safety profile, may reduce haematoma growth. METHODS AND DESIGN: Stopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units (STOP-MSU) is a phase II double-blind, randomised, placebo-controlled, multicentre, international investigator-led clinical trial, conducted within the estimand statistical framework. HYPOTHESIS: In patients with spontaneous ICH, treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo. SAMPLE SIZE ESTIMATES: A sample size of 180 patients (90 in each arm) would be required to detect an absolute difference in the primary outcome of 20% (placebo 39% vs treatment 19%) under a two-tailed significance level of 0.05. An adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients. INTERVENTION: Participants will receive 1 g intravenous tranexamic acid over 10 min, followed by 1 g intravenous tranexamic acid over 8 hours; or matching placebo. PRIMARY EFFICACY MEASURE: The primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours, defined as either ≥33% relative increase or ≥6 mL absolute increase in haematoma volume between baseline and follow-up CT scan. DISCUSSION: We describe the rationale and protocol of STOP-MSU, a phase II trial of tranexamic acid in patients with ICH within 2 hours from onset, based in participating mobile stroke units and emergency departments.

Use of the Estimand Framework to Manage the Disruptive Effects of COVID-19 on Stroke Clinical Trials.

The coronavirus disease 2019 (COVID-19) pandemic has presented unique challenges to stroke care and research internationally. In particular, clinical trials in stroke are vulnerable to the impacts of the pandemic at multiple stages, including design, recruitment, intervention, follow-up, and interpretation of outcomes. A carefully considered approach is required to ensure the appropriate conduct of stroke trials during the pandemic and to maintain patient and participant safety. This has been recently addressed by the International Council for Harmonisation which, in November 2019, released an addendum to the Statistical Principles for Clinical Trials guidelines entitled Estimands and Sensitivity Analysis in Clinical Trials. In this article, we present the International Council for Harmonisation estimand framework for the design and conduct of clinical trials, with a specific focus on its application to stroke clinical trials. This framework aims to align the clinical and scientific objectives of a trial with its design and end points. It also encourages the prospective consideration of potential postrandomization intercurrent events which may occur during a trial and either impact the ability to measure an end point or its interpretation. We describe the different categories of such events and the proposed strategies for dealing with them, specifically focusing on the COVID-19 pandemic as a source of intercurrent events. We also describe potential practical impacts posed by the COVID-19 pandemic on trials, health systems, study groups, and participants, all of which should be carefully reviewed by investigators to ensure an adequate practical and statistical strategy is in place to protect trial integrity. We provide examples of the implementation of the estimand framework within hypothetical stroke trials in intracerebral hemorrhage and stroke recovery. While the focus of this article is on COVID-19 impacts, the strategies and principles proposed are well suited for other potential events or issues, which may impact clinical trials in the field of stroke.

SARS-CoV-2 and Stroke Characteristics: A Report From the Multinational COVID-19 Stroke Study Group.

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COVID-19 Pandemic Impact on Care for Stroke in Australia: Emerging Evidence From the Australian Stroke Clinical Registry.

We present information on acute stroke care for the first wave of the COVID-19 pandemic in Australia using data from the Australian Stroke Clinical Registry (AuSCR). The first case of COVID-19 in Australia was recorded in late January 2020 and national restrictions to control the virus commenced in March. To account for seasonal effects of stroke admissions, patient-level data from the registry from January to June 2020 were compared to the same period in 2019 (historical-control) from 61 public hospitals. We compared periods using descriptive statistics and performed interrupted time series analyses. Perceptions of stroke clinicians were obtained from 53/72 (74%) hospitals participating in the AuSCR (80% nurses) via a voluntary, electronic feedback survey. Survey data were summarized to provide contextual information for the registry-based analysis. Data from the registry covered locations that had 91% of Australian COVID-19 cases to the end of June 2020. For the historical-control period, 9,308 episodes of care were compared with the pandemic period (8,992 episodes). Patient characteristics were similar for each cohort (median age: 75 years; 56% male; ischemic stroke 69%). Treatment in stroke units decreased progressively during the pandemic period (control: 76% pandemic: 70%, p < 0.001). Clinical staff reported fewer resources available for stroke including 10% reporting reduced stroke unit beds. Several time-based metrics were unchanged whereas door-to-needle times were longer during the peak pandemic period (March-April, 2020; 82 min, control: 74 min, p = 0.012). Our data emphasize the need to maintain appropriate acute stroke care during times of national emergency such as pandemic management.