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The INTREPID trial tests whether fever prevention surpasses standard temperature management in acute ischemic or hemorrhagic stroke patients. The study is prospective, randomized with blinded endpoints, using the Arctic Sun System, targeting 37.0°C and measuring total fever burden above 37.9°C (°C-h) plus modified Rankin Scale at 3 months.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/impact-of-fever-prevention-in-brain-injured-patients-intrepid-study-protocol-for-a-randomized-controlled-trial/156157/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/impact-of-fever-prevention-in-brain-injured-patients-intrepid-study-protocol-for-a-randomized-controlled-trial/156157.png","ImageObject",300,407,{"name":92,"@type":93},"Miles","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-17","2026-08-28",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the primary objective of the INTREPID trial?","Question",{"text":112,"@type":113},"To test the hypothesis that fever prevention is superior to standard temperature management in patients with acute vascular brain injury.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does the fever prevention intervention work in INTREPID?",{"text":117,"@type":113},"Fever prevention uses the Arctic Sun System, compared against usual care where fever may develop spontaneously.",{"name":119,"@type":110,"acceptedAnswer":120},"What outcomes does the trial measure to evaluate effectiveness?",{"text":121,"@type":113},"The primary efficacy outcome is total fever burden above 37.9°C, expressed as °C-h. The primary secondary outcome is the modified Rankin Scale at 3 months.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},156157,1787954489,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":129,"read_time":144,"preview_page_count":4},13056703019404,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Neurocrit Care  \n[https://doi.org/10.1007/s12028-021-01208-1](https://doi.org/10.1007/s12028-021-01208-1)  \nSPECIAL ARTICLE  \nImpact of Fever Prevention in Brain-Injured Patients (INTREPID): Study Protocol for a Randomized Controlled Trial  \nDavid M. Greer 1*, Jaime Ritter2, Raimund Helbok3, Neeraj Badjatia4, Sang‑Bae Ko 1, Mary Guanci5 and Kevin N. Sheth6  \n© 2021 Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society  \nAbstract  \nBackground: Multiple studies demonstrate that fever/elevated temperature is associated with poor outcomes inpatients 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 tem‑ perature management in patients with acute vascular brain injury.  \nMethods: INTREPID is a prospective randomized open blinded endpoint study offever 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, intrac‑ erebral 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 sam‑ ple 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 inpatients with acute stroke ([www.clinicaltrials.gov](www.clinicaltrials.gov); NCT02996266; registered prospectively 05DEC2016) .  \nKeywords: Fever, Normothermia, Ischemic stroke, Intracerebral hemorrhage, Subarachnoid hemorrhage, Prevention  \nBackground  \nThere has been significant attention in recent studies exploring the use of targeted temperature management  \n*Correspondence: [dgreer@bu.edu](dgreer@bu.edu)  \n1 Department of Neurology, Boston University School of Medicine, Boston Medical Center, Collamore 3, Suite 338, 72 East Concord Street, Boston, MA, USA  \nFull list of author information is available at the end of the article  \n(TTM) to improve outcomes in a variety of brain-injured patients, including those with vascular brain injury. Induced therapeutic hypothermia (TH) has garnered particular interest, but is not without its potential adverse effects such as cardiac dysrhythmia, increased infection and bleeding risk. Additionally, significant doses of sedatives and/or paralytics, which can confound neurologic assessment, are often required to  \ncontrol shivering in TH patients. Finally, TH delays drug metabolism and has shown detrimental effects on the ability to prognosticate neurologically [1, 2]. Controlled normothermia may prove to be an effective method of preventing secondary injury and improving neurological outcomes after acute vascular brai","cbCaigNlSc93f3sD","https://ap.wps.com/l/cbCaigNlSc93f3sD","pdf",883147,13,"English","# Background\n## Link between fever and outcomes in vascular brain injury\n# Methods\n## Trial design and intervention\n## Population, timing, and treatment duration\n## Outcomes and statistical approach\n# Discussion\n## Expected impact of the fever prevention strategy","[{\"question\":\"What is the primary objective of the INTREPID trial?\",\"answer\":\"To test the hypothesis that fever prevention is superior to standard temperature management in patients with acute vascular brain injury.\"},{\"question\":\"How does the fever prevention intervention work in INTREPID?\",\"answer\":\"Fever prevention uses the Arctic Sun System, compared against usual care where fever may develop spontaneously.\"},{\"question\":\"What outcomes does the trial measure to evaluate effectiveness?\",\"answer\":\"The primary efficacy outcome is total fever burden above 37.9°C, expressed as °C-h. The primary secondary outcome is the modified Rankin Scale at 3 months.\"}]","Impact of Fever Prevention in Brain-Injured Patients (INTREPID) - Study Protocol for a Randomized Controlled Trial | PDF",33]