The REACT study: design of a randomized phase 3 trial to assess the efficacy and safety of clazosentan for preventing deterioration due to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage
Abstract Background For patients presenting with an aneurysmal subarachnoid hemorrhage (aSAH), delayed cerebral ischemia (DCI) is a significant cause of morbidity and mortality. The REACT study is designed to assess the safety and efficacy of clazosentan in preventing clinical deterioration due to D...
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BMC
2022-12-01
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| Series: | BMC Neurology |
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| Online Access: | https://doi.org/10.1186/s12883-022-03002-8 |
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| author | Nicolas Bruder Randall Higashida Hugues Santin-Janin Cécile Dubois E. François Aldrich Angelina Marr Sébastien Roux Stephan A. Mayer |
| author_facet | Nicolas Bruder Randall Higashida Hugues Santin-Janin Cécile Dubois E. François Aldrich Angelina Marr Sébastien Roux Stephan A. Mayer |
| author_sort | Nicolas Bruder |
| collection | DOAJ |
| description | Abstract Background For patients presenting with an aneurysmal subarachnoid hemorrhage (aSAH), delayed cerebral ischemia (DCI) is a significant cause of morbidity and mortality. The REACT study is designed to assess the safety and efficacy of clazosentan in preventing clinical deterioration due to DCI in patients with aSAH. Methods REACT is a prospective, multicenter, randomized phase 3 study that is planned to enroll 400 patients with documented aSAH from a ruptured cerebral aneurysm, randomized 1:1 to 15 mg/hour intravenous clazosentan vs. placebo, in approximately 100 sites and 15 countries. Eligible patients are required to present at hospital admission with CT evidence of significant subarachnoid blood, defined as a thick and diffuse clot that is more than 4 mm in thickness and involves 3 or more basal cisterns. The primary efficacy endpoint is the occurrence of clinical deterioration due to DCI up to 14 days post-study drug initiation. The main secondary endpoint is the occurrence of clinically relevant cerebral infarction at Day 16 post-study drug initiation. Other secondary endpoints include the modified Rankin Scale (mRS) and the Glasgow Outcome Scale-Extended (GOSE) score at Week 12 post-aSAH, dichotomized into poor and good outcome. Radiological results and clinical endpoints are centrally evaluated by independent committees, blinded to treatment allocation. Exploratory efficacy endpoints comprise the assessment of cognition status at 12 weeks and quality of life at 12 and 24 weeks post aSAH. Discussion In the REACT study, clazosentan is evaluated on top of standard of care to determine if it reduces the risk of clinical deterioration due to DCI after aSAH. The selection of patients with thick and diffuse clots is intended to assess the benefit/risk profile of clazosentan in a population at high risk of vasospasm-related ischemic complications post-aSAH. Trial registration (Additional file 1) ClinicalTrials.gov (NCT03585270). EU Clinical Trial Register (EudraCT Number: 2018–000241-39). |
| first_indexed | 2024-04-11T05:06:54Z |
| format | Article |
| id | doaj.art-d6310e62d9c64dffab5591391eeeeb36 |
| institution | Directory Open Access Journal |
| issn | 1471-2377 |
| language | English |
| last_indexed | 2024-04-11T05:06:54Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neurology |
| spelling | doaj.art-d6310e62d9c64dffab5591391eeeeb362022-12-25T12:20:27ZengBMCBMC Neurology1471-23772022-12-0122111510.1186/s12883-022-03002-8The REACT study: design of a randomized phase 3 trial to assess the efficacy and safety of clazosentan for preventing deterioration due to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhageNicolas Bruder0Randall Higashida1Hugues Santin-Janin2Cécile Dubois3E. François Aldrich4Angelina Marr5Sébastien Roux6Stephan A. Mayer7Department of Anesthesia and Critical Care, Hôpital de la Timone, Aix-Marseille UniversitéDepartment of Neuro Interventional Radiology, University of California San Francisco Medical CenterBiometry, Idorsia Pharmaceuticals LtdBiometry, Idorsia Pharmaceuticals LtdDepartment of Neurosurgery, University of MarylandGlobal Clinical Development, Idorsia Pharmaceuticals LtdGlobal Clinical Development, Idorsia Pharmaceuticals LtdNeurocritical Care and Emergency Neurology Services, Westchester Medical Center Health NetworkAbstract Background For patients presenting with an aneurysmal subarachnoid hemorrhage (aSAH), delayed cerebral ischemia (DCI) is a significant cause of morbidity and mortality. The REACT study is designed to assess the safety and efficacy of clazosentan in preventing clinical deterioration due to DCI in patients with aSAH. Methods REACT is a prospective, multicenter, randomized phase 3 study that is planned to enroll 400 patients with documented aSAH from a ruptured cerebral aneurysm, randomized 1:1 to 15 mg/hour intravenous clazosentan vs. placebo, in approximately 100 sites and 15 countries. Eligible patients are required to present at hospital admission with CT evidence of significant subarachnoid blood, defined as a thick and diffuse clot that is more than 4 mm in thickness and involves 3 or more basal cisterns. The primary efficacy endpoint is the occurrence of clinical deterioration due to DCI up to 14 days post-study drug initiation. The main secondary endpoint is the occurrence of clinically relevant cerebral infarction at Day 16 post-study drug initiation. Other secondary endpoints include the modified Rankin Scale (mRS) and the Glasgow Outcome Scale-Extended (GOSE) score at Week 12 post-aSAH, dichotomized into poor and good outcome. Radiological results and clinical endpoints are centrally evaluated by independent committees, blinded to treatment allocation. Exploratory efficacy endpoints comprise the assessment of cognition status at 12 weeks and quality of life at 12 and 24 weeks post aSAH. Discussion In the REACT study, clazosentan is evaluated on top of standard of care to determine if it reduces the risk of clinical deterioration due to DCI after aSAH. The selection of patients with thick and diffuse clots is intended to assess the benefit/risk profile of clazosentan in a population at high risk of vasospasm-related ischemic complications post-aSAH. Trial registration (Additional file 1) ClinicalTrials.gov (NCT03585270). EU Clinical Trial Register (EudraCT Number: 2018–000241-39).https://doi.org/10.1186/s12883-022-03002-8AneurysmSubarachnoid hemorrhageCerebral vasospasmDelayed cerebral ischemiaClazosentan |
| spellingShingle | Nicolas Bruder Randall Higashida Hugues Santin-Janin Cécile Dubois E. François Aldrich Angelina Marr Sébastien Roux Stephan A. Mayer The REACT study: design of a randomized phase 3 trial to assess the efficacy and safety of clazosentan for preventing deterioration due to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage BMC Neurology Aneurysm Subarachnoid hemorrhage Cerebral vasospasm Delayed cerebral ischemia Clazosentan |
| title | The REACT study: design of a randomized phase 3 trial to assess the efficacy and safety of clazosentan for preventing deterioration due to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage |
| title_full | The REACT study: design of a randomized phase 3 trial to assess the efficacy and safety of clazosentan for preventing deterioration due to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage |
| title_fullStr | The REACT study: design of a randomized phase 3 trial to assess the efficacy and safety of clazosentan for preventing deterioration due to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage |
| title_full_unstemmed | The REACT study: design of a randomized phase 3 trial to assess the efficacy and safety of clazosentan for preventing deterioration due to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage |
| title_short | The REACT study: design of a randomized phase 3 trial to assess the efficacy and safety of clazosentan for preventing deterioration due to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage |
| title_sort | react study design of a randomized phase 3 trial to assess the efficacy and safety of clazosentan for preventing deterioration due to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage |
| topic | Aneurysm Subarachnoid hemorrhage Cerebral vasospasm Delayed cerebral ischemia Clazosentan |
| url | https://doi.org/10.1186/s12883-022-03002-8 |
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