Impact of Fever Prevention in Brain-Injured Patients (INTREPID): Study Protocol for a Randomized Controlled Trial.

BACKGROUND: Multiple studies demonstrate that fever/elevated temperature is associated with poor outcomes in patients with vascular brain injury; however, there are no conclusive studies that demonstrate that fever prevention/controlled normothermia is associated with better outcomes. The primary objective of the INTREPID (Impact of Fever Prevention in Brain-Injured Patients) trial is to test the hypothesis that fever prevention is superior to standard temperature management in patients with acute vascular brain injury. METHODS: INTREPID is a prospective randomized open blinded endpoint study of fever prevention versus usual care in patients with ischemic or hemorrhagic stroke. The fever prevention intervention utilizes the Arctic Sun System and will be compared to standard care patients in whom fever may spontaneously develop. Ischemic stroke, intracerebral hemorrhage or subarachnoid hemorrhage patients will be included within disease-specific time-windows. Both awake and sedated patients will be included, and treatment is initiated immediately upon enrollment. Eligible patients are expected to require intensive care for at least 72 h post-injury, will not be deemed unlikely to survive without severe disability, and will be treated for up to 14 days, or until deemed ready for discharge from the ICU, whichever comes first. Fifty sites in the USA and worldwide will participate, with a target enrollment of 1176 patients (1000 evaluable). The target temperature is 37.0 °C. The primary efficacy outcome is the total fever burden by °C-h, defined as the area under the temperature curve above 37.9 °C. The primary secondary outcome, on which the sample size is based, is the modified Rankin Scale Score at 3 months. All efficacy analyses including the primary and key secondary endpoints will be primarily based on an intention-to-treat population. Analysis of the as-treated and per protocol populations will also be performed on the primary and key secondary endpoints as sensitivity analyses. DISCUSSION: The INTREPID trial will provide the first results of the impact of a pivotal fever prevention intervention in patients with acute stroke ( www.clinicaltrials.gov ; NCT02996266; registered prospectively 05DEC2016).

Changes in Stroke Patients' Health-Seeking Behavior by COVID-19 Epidemic Regions: Data from the Korean Stroke Registry.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has led to changes in stroke patients' healthcare use. This study evaluated changes in Korean stroke patients' health-seeking behaviors and stroke care services using data from the Korean Stroke Registry (KSR). METHODS: We reviewed data from patients with acute stroke and transient ischemic attack (TIA) during 2019 (before COVID-19 period) and 2020 (COVID-19 period). Outcomes included patient characteristics, time from stroke onset to hospital arrival, and in-hospital stroke pathways. Subgroup analyses were performed for an epidemic region (Daegu city and Gyeongsangbuk-do region, the D-G region). RESULTS: The study included 1,792 patients from the pre-COVID-19 period and 1,555 patients from the COVID-19 period who visited hospitals that contribute to the KSR. During the COVID-19 period, the D-G region had two-thirds the number of cases (vs. the pre-CO-VID-19 period) and a significant decrease in the proportion of patients with TIA (9.97%-2.91%). Unlike other regions, the median onset-to-door time increased significantly in the D-G region (361 min vs. 526.5 min, p = 0.016), and longer onset-to-door times were common for patients with mild symptoms and who were in their 60s or 70s. The number of patients who underwent intravenous thrombolysis also decreased during the COVID-19 period, although the treatment times were not significantly different between the 2 periods. DISCUSSION/CONCLUSION: Korean stroke patients in a CO-VID-19 epidemic region exhibited distinct changes in health-seeking behaviors. Appropriate triage system and public education regarding the importance of early treatment are needed during the COVID-19 pandemic.

Modification of Acute Stroke Pathway in Korea After the Coronavirus Disease 2019 Outbreak.

Background: Since the global pandemic of coronavirus disease 2019 (COVID-19), the process of emergency medical services has been modified to ensure the safety of healthcare professionals as well as patients, possibly leading to a negative impact on the timely delivery of acute stroke care. This study aimed to assess the impact of the COVID-19 pandemic on the acute stroke care processes and outcomes in tertiary COVID-19-dedicated centers in South Korea. Methods: We included 1,213 patients with acute stroke admitted to three centers in three cities (Seoul, Seongnam, and Daegu) through the stroke critical pathway between September 2019 and May 2020 (before and during the COVID-19 pandemic). In all three centers, we collected baseline characteristics and parameters regarding the stroke critical pathway, including the number of admitted patients diagnosed with acute stroke through the stroke critical pathway, door to brain imaging time, door to intravenous recombinant tissue plasminogen activator time, door to groin puncture time, and door to admission time. We performed an interrupted time series analysis to determine the impact of the COVID-19 outbreak on outcomes and critical pathway parameters. Results: Three centers modified the protocol of the stroke critical pathway during the COVID-19 pandemic. There was an immediate decrease in the number of patients admitted with acute ischemic stroke after the outbreak of COVID-19 in Korea, especially in the center of Daegu, an epicenter of the COVID-19 outbreak. However, the number of patients with stroke soon increased to equal that before the Covid-19 outbreak. In several critical pathway parameters, door to imaging time showed a temporary increase, and door to admission was transiently decreased after the COVID-19 outbreak. However, there was no significant effect on the timely trend. Moreover, there was no significant difference in the baseline characteristics and clinical outcomes between the periods before and during the COVID-19 pandemic. Conclusion: This study demonstrated that the COVID-19 outbreak immediately affected the management process. However, it did not have a significant overall impact on the trends of stroke treatment processes and outcomes. The stroke management process should be modified according to changing situations for optimal acute management.