Pivlaz (clazosentan) / Idorsia, Nxera Pharma - LARVOL DELTA

Early Positive Fluid Balance as a Clinical Marker of Systemic Capillary Leak and Clazosentan Intolerance After Aneurysmal Subarachnoid Hemorrhage. (PubMed, Neurocrit Care) - "Early positive fluid balance was a strong independent predictor of clazosentan discontinuation and was associated with poor functional outcomes. Early postoperative fluid balance may serve as a practical bedside marker of clazosentan intolerance and fluid-retentive physiological response, potentially involving increased vascular permeability. Goal-directed fluid management targeting euvolemia during the first 72 h may help optimize tolerability and enhance the therapeutic efficacy of clazosentan."

Journal • Cardiovascular • Hematological Disorders • Subarachnoid Hemorrhage

The beneficial effects of clazosentan on the perioperative management of patients with subarachnoid hemorrhage. (PubMed, Neurosurg Rev) - "Furthermore, the length of hospital stay was significantly shorter in the clazosentan group than in the fasudil group (22.3 days vs. 29.6 days, p < 0.01). Conclusion clazosentan-based management was associated with reduced angiographic vasospasm, earlier rehabilitation, and shorter hospitalization compared with fasudil-based management."

Journal • Cardiovascular • Hematological Disorders • Subarachnoid Hemorrhage

Machine Learning-Identified Potential Interaction Between Clazosentan and Nicardipine in Patients with Subarachnoid Hemorrhage. (PubMed, J Clin Med) - "A potential interaction with nicardipine was linked to higher odds of AVS (OR 1.85 [1.43-2.65]). Clazosentan was associated with reduced VS and improved 6-month outcomes after aSAH, although concomitant nicardipine may attenuate its prophylactic effectiveness against AVS."

Journal • Cardiovascular • CNS Disorders • Hematological Disorders • Subarachnoid Hemorrhage

Cost-Effectiveness Framework to Evaluate Therapeutic Interventions Targeting Reduction in Cerebral Infarction Among Aneurysmal Subarachnoid Hemorrhage Patients (ISC 2026) - "We present a cost-effectiveness framework which allows pre-trial assessment based on the cost of a therapeutic intervention and the expected magnitude of reduction in occurrence of cerebral infarction in aSAH patients."

Clinical • Cost effectiveness • HEOR • Cardiovascular • CNS Disorders • Hematological Disorders • Subarachnoid Hemorrhage

A simulation study of the cost of cerebral vasospasm treatments with clazosentan: A mathematical model using time-driven activity-based costing. (PubMed, PLoS One) - "We compared two treatment approaches: conventional therapy with fasudil hydrochloride and postoperative therapy with clazosentan. Clazosentan for subarachnoid haemorrhage treatment significantly reduces human resource costs, especially in nursing staff. These findings support the potential of clazosentan for broader clinical use, given its cost-savings and clinical benefits in reducing cerebral vasospasm following aneurysmal subarachnoid haemorrhage."

Journal • Cardiovascular • Subarachnoid Hemorrhage

Clazosentan Affects Temporal Profile of Endothelin-A Expression in Macro- and Microcirculation after Subarachnoid Hemorrhage. (PubMed, Neurol Med Chir (Tokyo)) - "In microvessels, pericyte density transiently decreased, peaking at a nadir on day 3 post-subarachnoid hemorrhage, while endothelin-A receptor expression on pericytes was highest at the same time point, and further elevated by clazosentan treatment. These findings indicate that clazosentan induces endothelin-A receptor upregulation in both macro- and microcirculation, potentially contributing to recurrent vasospasm after treatment, and highlight the critical role of pericytes in post-subarachnoid hemorrhage vascular regulation."

Journal • Hematological Disorders • Subarachnoid Hemorrhage • CD31 • PECAM1

Detrimental effect of early clazosentan administration on neurogenic pulmonary edema following subarachnoid hemorrhage and safety of its delayed administration: Laboratory investigation. (PubMed, World Neurosurg) - "While the early administration of clazosentan exacerbated SAH-induced NPE, delayed administration did not exhibit this detrimental effect. Clazosentan may safely be utilized in clinical settings for patients with SAH who develop NPE, provided that NPE shows improvement."

Journal • Cardiovascular • Hematological Disorders • Respiratory Diseases • Subarachnoid Hemorrhage

A patient-derived CRISPR platform reveals selective dependencies in Acute Myeloid Leukemia (ASH 2025) - "Our results indicate that EDNRAknockout inhibits AML cell proliferation and growth, highlighting its potential as a therapeutic target.Furthermore, EDNRA is overexpressed in AML compared to normal cells, and since FDA approved EDNRAinhibitors such as Macitentan, Bosentan, Ambrisentan, and Clazosentan are already being used to treatpulmonary arterial hypertension, this presents a promising opportunity to evaluate these inhibitors aspotential chemotherapy-sensitizing agents for high-risk AML.SOD1 plays a critical role in eliminating toxicradicals generated within biological systems and has been associated with poor outcomes in AML. This study demonstrates the establishment of a scalable platform for CRISPR screening inprimary AML cells for identification of more conserved vulnerabilities that may be exploitedtherapeutically, with EDNRA as a potential target. Ongoing work includes validating key targets with thegoal of advancing therapeutic strategies. Future studies will..."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Pulmonary Arterial Hypertension • Respiratory Diseases • EDNRA • HOXA9 • MEIS1 • PPM1D • SUZ12

Stratified assessment of clazosentan efficacy following subarachnoid hemorrhage: A multi-center cohort study. (PubMed, J Cereb Blood Flow Metab) - "Stratification analyses revealed that clazosentan usage increased the incidence of favorable functional outcomes regardless of age, sex, SAH severity, and clot volume. These results underscore the therapeutic potential of clazosentan against cerebral vasospasm independent of patient characteristics."

Journal • Cardiovascular • Hematological Disorders • Subarachnoid Hemorrhage

Potential for multidrug combination therapy in patients with World Federation of Neurological Surgeons grade V subarachnoid hemorrhage. (PubMed, Neurosurg Rev) - "This study aimed to investigate whether any of the drugs currently used in Japan, where nimodipine is not approved, are effective for WFNS grade V SAH patients...Multivariate analyses revealed that pre-onset mRS 1-2, admission modified Fisher grade 4, ruptured middle cerebral artery aneurysm, acute hydrocephalus, and older age were independently associated with poor outcomes, while combination drug therapy with fasudil hydrochloride (Rho-kinase inhibitor) + cilostazol (phosphodiesterase type III inhibitor) + eicosapentaenoic acid (omega-3 polyunsaturated fatty acid) or clazosentan (endothelin receptor subtype A antagonist) + cilostazol was the only independent determinant of good outcomes. The combination drug therapies were also independent inhibitors of delayed cerebral infarction (non-iatrogenic cerebral infarction on computed tomography after SAH), but not of cerebral vasospasm (≥ 50% angiographic vasospasm of a major cerebral artery) and rescue therapy (endovascular..."

Journal • Retrospective data • Cardiovascular • CNS Disorders • Hematological Disorders • Subarachnoid Hemorrhage • Ventriculomegaly

Impact of Clazosentan Use on Symptomatic Vasospasm and Early Ambulation in Patients with Aneurysmal Subarachnoid Hemorrhage: A Retrospective Cohort Study. (PubMed, Neurol Med Chir (Tokyo)) - "Secondary outcomes included changes in body weight, peripheral oxygen saturation, and laboratory parameters one week after drug administration.The incidence of symptomatic vasospasm was significantly lower in the clazosentan group (5.3%) than in the conventional treatment group (20.7%) (p = 0.007). In addition, ambulation was achieved significantly earlier in the clazosentan group (median: 8.5 days; interquartile range: 5-12) than in the control group (median: 11 days, interquartile range: 8-15) (p = 0.015).Conversely, one week after administration, the clazosentan group showed a significant increase in body weight and significant decreases in peripheral oxygen saturation, serum albumin, hemoglobin, and hematocrit levels, suggesting potential systemic effects.These findings suggest that clazosentan use may be associated with a lower incidence of symptomatic vasospasm and earlier ambulation in patients with aneurysmal subarachnoid hemorrhage; however, careful monitoring..."

Journal • Retrospective data • Cardiovascular • Hematological Disorders • Subarachnoid Hemorrhage

Risk factors for fluid retention associated with clazosentan after subarachnoid hemorrhage: a retrospective study. (PubMed, Neurol Res) - "Older age and early fluid accumulation emerged as significant risk factors for fluid retention in patients treated with clazosentan. In older individuals, close monitoring and careful fluid balance management may help prevent clazosentan-associated complications."

Journal • Retrospective data • Cardiovascular • Critical care • Hematological Disorders • Respiratory Diseases • Subarachnoid Hemorrhage

Prognostic factors in aneurysmal subarachnoid hemorrhage during the clazosentan era: a multicenter study using multivariate analyses and machine learning model. (PubMed, Neurosurg Rev) - "Clinical status at aSAH onset and age are uncontrollable factors; therefore, improving prognosis requires targeted prevention of DCI and effective management of brain edema. The administration of therapies such as clazosentan, cilostazol, and statins may contribute to favorable outcomes."

Biomarker • Clinical • Journal • Observational data • Retrospective data • Cardiovascular • CNS Disorders • Hematological Disorders • Subarachnoid Hemorrhage

Clazosentan for cerebral vasospasm prevention in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. (PubMed, BMC Neurol) - "While clazosentan effectively prevents cerebral vasospasm following aSAH, particularly at higher doses in surgically treated patients, its clinical utility must be weighed against significant systemic adverse effects. These findings support selective use in high-risk patients while highlighting the need for careful monitoring and individualized treatment approaches."

Journal • Retrospective data • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Hypotension • Subarachnoid Hemorrhage

Evaluating clazosentan sodium for the treatment of aneurysmal subarachnoid hemorrhage. (PubMed, Expert Rev Neurother) - "Nimodipine remains the only FDA-approved drug for DCI prevention. Recent Japanese Phase III trials and real-world cohorts suggest benefit in selected populations and practice settings, supporting clazosentan as an adjunct to standard care rather than a replacement. Further work should refine dosing, patient selection, and combination strategies that target microvascular dysfunction and neuroinflammation beyond large-vessel spasm."

Journal • Review • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Inflammation • Subarachnoid Hemorrhage

Efficacy of combined clazosentan and cilostazol therapy for cerebral vasospasm after subarachnoid hemorrhage: a retrospective multicenter registry study. (PubMed, J Neurosurg) - "The combination of clazosentan and cilostazol may reduce the incidence of DCI, although its impact on functional outcomes remains unclear. Further research is warranted to explore effective pharmacological strategies for improving the prognosis of aSAH."

Clinical • Journal • Retrospective data • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Hypotension • Subarachnoid Hemorrhage • Vascular Neurology

Prognosis-anchored outcome evaluation (PAOE) for detecting functional benefit in aSAH: A multicenter analysis of clazosentan use. (PubMed, J Clin Neurosci) - "PAOE provides a complementary approach to traditional cohort or RCT analyses by accounting for individual prognostic expectations. Our findings support the hypothesis that clazosentan may offer functional benefit in selected aSAH patients with moderate predicted disability. This approach may help identify patients who are most likely to benefit from vasospasm-targeted interventions in clinical practice."

Journal • Cardiovascular • Hematological Disorders • Subarachnoid Hemorrhage

Quantitative evaluation of the vasodilatory effect of clazosentan in preventing cerebral vasospasm after subarachnoid hemorrhage. (PubMed, Interv Neuroradiol) - "However, its limited effect on proximal arteries suggests a need for supplementary treatments targeting these regions to improve clinical outcomes. Differences in vasodilatory effect at various sites may be associated with the controversy regarding clazosentan's clinical effects."

Journal • Cardiovascular • Hematological Disorders • Subarachnoid Hemorrhage

Successful Management of Subarachnoid Hemorrhage Complicated by Takotsubo Cardiomyopathy Using Distal Transradial Access (dTRA) Coiling and Integrated Pharmacotherapy Under Intra-aortic Balloon Pumping (IABP) Support: A Stroke-Heart Syndrome Case. (PubMed, Cureus) - "We report the case of a 55-year-old woman with SAH and severe TCM treated successfully through multidisciplinary care involving intra-aortic balloon pumping (IABP), endovascular aneurysm coiling via distal transradial access (dTRA), and a structured pharmacologic strategy, following hemodynamic stabilization, that included angiotensin receptor-neprilysin inhibitors (ARNIs), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), clazosentan, and perampanel. This case illustrates the feasibility of managing complex neurocardiac comorbidity using integrative, anticipatory strategies in a high care unit (HCU) managed directly by neurosurgeons, outside a formal intensive care unit (ICU)."

Journal • Cardiomyopathy • Cardiovascular • Critical care • Hematological Disorders • Subarachnoid Hemorrhage

Japanese Nationwide Questionnaire Survey on the Treatment and Management of Subarachnoid Hemorrhage Due to Ruptured Cerebral Aneurysm. (PubMed, J Clin Med) - "For both craniotomy and endovascular surgery, clazosentan was used most frequently, followed by cilostazol, fasudil, and statins. The impression of the effectiveness in preventing DCI and the outcomes of clazosentan have been mixed. As data accumulate, clazosentan use and management protocols will be refined and developed."

Journal • Cardiovascular • Hematological Disorders • Respiratory Diseases • Subarachnoid Hemorrhage • Vascular Neurology

Clinical factors associated with delayed ischemic and non-ischemic adverse events in clazosentan therapy after aneurysmal subarachnoid hemorrhage: early insights from a multicenter prospective registry. (PubMed, Neurosurg Rev) - "Addressing clinical risk factors for non-ischemic adverse events may further enhance treatment outcomes. Clinical trial number Not applicable."

Adverse events • Journal • Cardiovascular • CNS Disorders • Hematological Disorders • Respiratory Diseases • Subarachnoid Hemorrhage

Multicenter Validation of a Unified Evidence-Based Treatment Protocol Focusing on Clazosentan for Managing Subarachnoid Hemorrhage. (PubMed, J Clin Med) - "Cases treated between April 2022 and March 2024 were categorized into four groups: preprotocol fasudil treatment (PrF), preprotocol clazosentan treatment (PrC), postprotocol fasudil treatment (PoF), and postprotocol clazosentan treatment (PoC); these groups were analyzed. Clazosentan-first protocol effectively reduces vasospasm and complications in aSAH management. It is also safe for older patients and those with WFNS grade V, offering a promising treatment strategy."

Journal • Cardiovascular • Hematological Disorders • Subarachnoid Hemorrhage

Emerging Advances in the Management of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Narrative Review. (PubMed, J Clin Med) - "Pharmacological approaches such as nimodipine, clazosentan, and fasudil have shown varying degrees of efficacy...Endovascular therapy and adjunctive agents such as cilostazol or anticoagulants have demonstrated potential but require further validation through large-scale trials. Effective DCI prevention and treatment require a multimodal approach targeting diverse pathological mechanisms beyond vasospasm. Improved risk stratification, early detection, and individualized therapy are essential for advancing the management of patients with aSAH."

Journal • Review • Cardiovascular • Hematological Disorders • Subarachnoid Hemorrhage

RECOVER study: a multicenter retrospective cohort study and comparison of the efficacy and safety of clazosentan and fasudil in patients with aneurysmal subarachnoid hemorrhage. (PubMed, J Neurosurg) - "Clazosentan outperformed fasudil in preventing cerebral vasospasm and improving overall outcomes in patients with aSAH. Despite initial concerns regarding fluid retention, appropriate perioperative management mitigated these risks, making clazosentan a superior treatment option across different patient groups."

Journal • Retrospective data • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Hypotension • Subarachnoid Hemorrhage

Risk factors for clazosentan-induced fluid retention in subarachnoid hemorrhage from the Japanese adverse event database. (PubMed, J Stroke Cerebrovasc Dis) - "Clazosentan-induced fluid retention occurred more frequently in older adult patients. Clazosentan combined with fasudil hydrochloride increased the incidence of fluid retention. These findings can guide pharmacological treatment of cerebral vasospasm in patients with subarachnoid hemorrhage."

Adverse events • Journal • Hematological Disorders • Subarachnoid Hemorrhage