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The purpose of the study is to measure how effective and safe three different doses of the drug clazosentan are in preventing vasospasm after subarachnoid hemorrhage.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Clazosentan 1 mg/h | Experimental | intravenous clazosentan at 1 mg/h starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture |
|
| Clazosentan 5 mg/h | Experimental | intravenous clazosentan at 5 mg/h starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture |
|
| Clazosentan 15 mg/h | Experimental | intravenous clazosentan at of 15 mg/h starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture |
|
| Placebo | Placebo Comparator | intravenous placebo starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clazosentan 1 mg/h | Drug | Subjects receive intravenous clazosentan at a rate of 1 mg/h starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture |
| Measure | Description | Time Frame |
|---|---|---|
| Occurrence of moderate or severe cerebral vasospasm, as measured by cerebral angiography | If the patient develops clinical or sonographic changes suggestive of vasospasm prior to or after Day 9 ± 2 and until Day 14 post-aneurysm rupture, an angiogram will be performed to confirm the vasospasm. If vasospasm is documented prior to Day 9 ± 2, the Day 9 ± 2 angiogram is no longer required. In the case that a patient only develops clinical symptoms suggestive of vasospasm later than Day 9 ± 2 and up to Day 14, an additional angiogram should be performed to confirm the diagnosis of vasospasm. If the latter shows a higher grade of vasospasm than the previous one, it will be used for comparison to the baseline angiogram for evaluation of the primary endpoint. | Up to day 14 |
| Measure | Description | Time Frame |
|---|---|---|
| Occurrence of vasospasm-related morbidity, and mortality of all causes defined as the occurrence of death of any cause within the first 6 weeks post-aneurysm rupture OR | Within 6 weeks | |
| Occurrence of vasospasm-related morbidity, and mortality of all causes defined as the occurence of new cerebral infarct within first 6 weeks post-aneurysm rupture based on local investigator reading of post-baseline CT scans OR |
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Inclusion criteria:
Exclusion criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dr. Giuseppe Lanzino | Peoria | Illinois | United States | |||
| Dr. Horner |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31299650 | Derived | Eagles ME, Powell MF, Ayling OGS, Tso MK, Macdonald RL. Acute kidney injury after aneurysmal subarachnoid hemorrhage and its effect on patient outcome: an exploratory analysis. J Neurosurg. 2019 Jul 12;133(3):765-772. doi: 10.3171/2019.4.JNS19103. Print 2020 Sep 1. | |
| 29946013 | Derived | Ayling OGS, Ibrahim GM, Alotaibi NM, Gooderham PA, Macdonald RL. Anemia After Aneurysmal Subarachnoid Hemorrhage Is Associated With Poor Outcome and Death. Stroke. 2018 Aug;49(8):1859-1865. doi: 10.1161/STROKEAHA.117.020260. |
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|
| Clazosentan 5 mg/h | Drug | Subjects receive intravenous clazosentan at a rate of 5 mg/h starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture |
|
|
| Clazosentan 15 mg/h | Drug | Subjects receive intravenous clazosentan at a rate of 15 mg/h starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture |
|
|
| Placebo | Drug | Subjects receive intravenous placebo starting within 56 hours maximum after aneurysm rupture and continuing until Day 14 post-aneurysm rupture |
|
| Within 6 weeks |
| Occurrence of vasospasm-related morbidity, and mortality of all causes defined as the occurence of delayed ischemic neurological deficits (DIND) due to vasospasm (based on investigator assessments) within 14 days post-aneurysm rupture OR | Within 14 days |
| Occurrence of vasospasm-related morbidity, and mortality of all causes defined as occurrence of use of rescue medication due to vasospasm within 14 days post-aneurysm rupture | Within 14 days |
| Clinical outcome at 12 weeks post-aneurysm rupture as measured by the Modified Rankin Scale (mRS) score | At 12 weeks |
| Clinical outcome at 12 weeks post-aneurysm rupture as measured bythe Glasgow Outcome Scale - Extended Version (GOSE) score | At 12 weeks |
| Indianapolis |
| Indiana |
| United States |
| Dr. Aldrich | Baltimore | Maryland | United States |
| Dr. Ogilvy | Boston | Massachusetts | United States |
| Dr. Zuccarello | Cincinnati | Ohio | United States |
| Dr. Woo | Cleveland | Ohio | United States |
| Dr. Rosenwasser | Philadelphia | Pennsylvania | United States |
| Dr. Zager | Philadelphia | Pennsylvania | United States |
| Dr. George A. Lopez | Houston | Texas | United States |
| Dr. Bullock | Richmond | Virginia | United States |
| Dr. Wong | Calgary | Alberta | Canada |
| Dr. Findlay | Edmonton | Alberta | Canada |
| Dr. Redekop | Vancouver | British Columbia | Canada |
| Dr. Ferguson | Toronto | Ontario | Canada |
| Dr. Bojanowski | Montreal | Quebec | Canada |
| Dr. Fleetwood | Halifax, Nova Scotia | Canada |
| 27827324 | Derived | Ayling OG, Ibrahim GM, Alotaibi NM, Gooderham PA, Macdonald RL. Dissociation of Early and Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage. Stroke. 2016 Dec;47(12):2945-2951. doi: 10.1161/STROKEAHA.116.014794. Epub 2016 Nov 8. |
| 27000643 | Derived | Nassiri F, Ibrahim GM, Badhiwala JH, Witiw CD, Mansouri A, Alotaibi NM, Macdonald RL. A Propensity Score-Matched Study of the Use of Non-steroidal Anti-inflammatory Agents Following Aneurysmal Subarachnoid Hemorrhage. Neurocrit Care. 2016 Dec;25(3):351-358. doi: 10.1007/s12028-016-0266-6. |
| 26428322 | Derived | Tso MK, Ibrahim GM, Macdonald RL. Predictors of Shunt-Dependent Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage. World Neurosurg. 2016 Feb;86:226-32. doi: 10.1016/j.wneu.2015.09.056. Epub 2015 Sep 30. |
| 26248048 | Derived | Young JM, Morgan BR, Misic B, Schweizer TA, Ibrahim GM, Macdonald RL. A Partial Least-Squares Analysis of Health-Related Quality-of-Life Outcomes After Aneurysmal Subarachnoid Hemorrhage. Neurosurgery. 2015 Dec;77(6):908-15; discussion 915. doi: 10.1227/NEU.0000000000000928. |
| 25280913 | Derived | Ibrahim GM, Macdonald RL. The network topology of aneurysmal subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry. 2015 Aug;86(8):895-901. doi: 10.1136/jnnp-2014-308992. Epub 2014 Oct 3. |
| 24425125 | Derived | Ibrahim GM, Morgan BR, Macdonald RL. Patient phenotypes associated with outcomes after aneurysmal subarachnoid hemorrhage: a principal component analysis. Stroke. 2014 Mar;45(3):670-6. doi: 10.1161/STROKEAHA.113.003078. Epub 2014 Jan 14. |
| 23581590 | Derived | Ibrahim GM, Fallah A, Macdonald RL. Clinical, laboratory, and radiographic predictors of the occurrence of seizures following aneurysmal subarachnoid hemorrhage. J Neurosurg. 2013 Aug;119(2):347-52. doi: 10.3171/2013.3.JNS122097. Epub 2013 Apr 12. |
| 22678087 | Derived | Ibrahim GM, Macdonald RL. Electrocardiographic changes predict angiographic vasospasm after aneurysmal subarachnoid hemorrhage. Stroke. 2012 Aug;43(8):2102-7. doi: 10.1161/STROKEAHA.112.658153. Epub 2012 Jun 7. |
| 21998061 | Derived | Ibrahim GM, Weidauer S, Vatter H, Raabe A, Macdonald RL. Attributing hypodensities on CT to angiographic vasospasm is not sensitive and unreliable. Stroke. 2012 Jan;43(1):109-12. doi: 10.1161/STROKEAHA.111.632745. Epub 2011 Oct 13. |
| ID | Term |
|---|---|
| D013345 | Subarachnoid Hemorrhage |
| D020301 | Vasospasm, Intracranial |
| ID | Term |
|---|---|
| D020300 | Intracranial Hemorrhages |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C109641 | clazosentan |
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