Abstract 43: Effect of Clazosentan on Clinical Outcome After Aneurysmal Subarachnoid Hemorrhage and Endovascular Coiling: Results of the CONSCIOUS-3 Study
Bibliographic record
Abstract
Introduction: In CONSCIOUS-1, clazosentan, an endothelin receptor antagonist, significantly and dose-dependently reduced angiographic vasospasm (VSP) after aneurysmal subarachnoid hemorrhage (aSAH). CONSCIOUS-3 aimed to assess whether clazosentan improves VSP-related morbidity/all cause mortality after aSAH. Methods: This was a randomized, double-blind, placebo-controlled trial. Patients included in the study were 18-75 years old with SAH due to ruptured saccular aneurysm secured by endovascular coiling, any thick clot and WFNS grades I-IV prior to coiling procedure. Patients were randomized 1:1:1 to intravenous clazosentan (5 or 15 mg/h) or placebo for ≤2 weeks. The primary composite endpoint (all-cause mortality; VSP-related new cerebral infarcts; delayed ischemic neurological deficit [DIND] due to VSP; rescue therapy in the presence of confirmed angiographic VSP) was evaluated 6 weeks post-aSAH and assessed centrally by a blinded critical events committee, with significance determined using logistic regression adjusted for WFNS. The main secondary endpoint was the extended Glasgow Outcome Scale (GOSE; dichotomized) at week 12. Results: CONSCIOUS-3 was halted prematurely following nonsignificant results from the parallel CONSCIOUS-2 clipping study. There were 571 treated patients (placebo n=189, clazosentan 5 mg/h n=194, clazosentan 15 mg/h n=188). The primary endpoint occurred in 27% of the placebo group compared with 24% and 15% in the 5 and 15 mg/h clazosentan groups, respectively; significant improvement was seen with 15 mg/h clazosentan (odds ratio [OR] 0.474, 95% CI 28-82%; p=0.007) but not 5 mg/h (OR 0.786, 95% CI 48-129%; p=0.340). DIND decreased with increasing clazosentan dose (placebo 21%; clazosentan 5 mg/h 18%; clazosentan 15 mg/h 10%). VSP-related new cerebral infarct occurred in 13%, 16% and 7% in the placebo, clazosentan 5 and 15 mg/h groups, respectively. A 3-fold greater use of rescue therapy was seen in patients receiving placebo (21%) compared with 15 mg/h clazosentan (7%). Poor functional outcome (GOSE score ≤4) occurred in 24% of patients in the placebo group compared with 25% (OR 0.918, 95% CI 55-154%; p=0.748) and 28% (OR 1.337, 95% CI 80-223%; p=0.266) in the clazosentan 5 and 15 mg/h groups, respectively. At week 12, mortality rates were 6%, 4% and 6% with placebo, clazosentan 5 and 15 mg/h, respectively. Treatment-emergent adverse events of specific interest were lung complications (21%, 36%, 37%), anemia (10%, 13%, 13%) and hypotension (7%, 11%, 16%) in the placebo, clazosentan 5 and 15 mg/h groups, respectively. Conclusions: Clazosentan (15 mg/h) significantly reduced mortality/VSP-related morbidity; however, no significant effect on GOSE occurred, possibly due to greater use of rescue therapy with placebo. Pulmonary complications, anemia and hypotension were more common in patients receiving clazosentan.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.003 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".