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

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

Treatment Outcomes of Clazosentan Use During the Perioperative Period for Subarachnoid Hemorrhage. (PubMed, Cureus) - "Background Fasudil hydrochloride hydrate has been traditionally administered in the perioperative management of aneurysmal subarachnoid hemorrhage (aSAH) in Japan for the prevention of delayed cerebral ischemia (DCI) secondary to cerebral vasospasm. While clazosentan showed a non-significant trend toward lower DCI frequency, it was associated with increased symptomatic pulmonary edema. Given the study's limitations, larger-scale research with matched baseline characteristics is needed to definitively evaluate these agents' comparative efficacy."

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

Effects of the Japanese traditional medicine Goreisan on adverse events affecting mucosal edema in patients with subarachnoid hemorrhage treated with clazosentan. (PubMed, Neurosurg Rev) - "Clazosentan combined with diuretics and Goreisan effectively reduced diarrhea and nasal mucosal swelling in patients with aSAH. This protocol may offer a viable approach for managing clazosentan-associated adverse events in aSAH patients."

Adverse events • Journal • Cardiovascular • Heart Failure • Hematological Disorders • Respiratory Diseases • Subarachnoid Hemorrhage

Clazosentan's Dual Edge Following Aneurysmal Subarachnoid Hemorrhage: A Systematic Review, Meta-Analysis, and Meta-Regression of Clinical Outcomes and Safety Profiles (AAN 2025) - "Clazosentan effectively reduces vasospasm-related complications in aSAH patients but is associated with increased risk of adverse effects. The findings underscore the need for carefully balancing benefits with risks, with further large-scale trials required to optimize dosing strategies and identify patient subgroups that may benefit most from clazosentan therapy."

Clinical data • Retrospective data • Review • Anemia • Cardiovascular • CNS Disorders • Hematological Disorders • Hypotension • Infectious Disease • Pneumonia • Respiratory Diseases • Subarachnoid Hemorrhage

SERIAL CBF ANALYSIS BY O15-WATER DYNAMIC PET DURING HYPERDYNAMIC THERAPY FOR VASOSPASM AFTER SAH (SCCM 2025) - "Although some prophylactics such as nimodipine and clazosentan have been approved for preventing vasospasm, DCI still unsatisfactorily solved...We aimed to clarify improved regional cerebral blood flow (rCBF) during the initial phase of inotropic hemodynamic augmentation induced by low-dose dobutamine (DOB) in postoperative patients diagnosed with radiological vasospasm and DCI... Low-dose DOB is a valuable initial rescue therapy for post-SAH symptomatic vasospasm to augment rCBF immediately after administration in vascular territories without diffuse vasospasm. This is the first qualitative CBF study to validate a mechanism of hyperdynamic therapy."

Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Subarachnoid Hemorrhage

Nxera Pharma Operational Highlights and Consolidated Results for the Fourth Quarter and Full Year 2024 (GlobeNewswire) - "Significant growth in PIVLAZ (clazosentan sodium) 150mg sales in Japan during first full year of Nxera ownership: Rapidly becoming standard of care in Japan with neurosurgeons for prevention of cerebral vasospasm in patients with aneurysmal subarachnoid haemorrhage (aSAH)....Q4 2024 net sales of JPY 4,282 million, FY 2024 net sales of JPY 12,651 million (US$83.5 million, representing 14% growth vs FY 2023)."

Sales • CNS Disorders • Subarachnoid Hemorrhage

Comparison of Clazosentan and Nimodipine on Vasospasm and Vasospasm-Related Outcomes after Aneurysmal Subarachnoid Hemorrhage : A Post-hoc Propensity Score-Matched Analysis of Six Randomized Clinical Trials. (PubMed, J Korean Neurosurg Soc) - "Clazosentan at 10 mg/h significantly reduced the incidence of cerebral vasospasm and MM following aSAH, compared to both placebo and nimodipine. Further clinical studies are warranted to compare the efficacy of clazosentan and nimodipine to optimize treatment strategies for aSAH."

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

Impact of Clazosentan on Vasospasm Reduction and Functional Recovery after Aneurysmal Subarachnoid Hemorrhage. (PubMed, Neurol Med Chir (Tokyo)) - "In every hospital in Japan, until 2022, the primary treatment for preventing delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) involved a combination of ozagrel sodium (Oz), fasudil hydrochloride (Fs), cilostazol, and statins. No significant difference was observed in the primary endpoint of functional outcome at discharge; however, a significant improvement in functional outcome was observed in the clazosentan group at 6 months (96.3% vs. 70.4%, p<0.05). Clazosentan significantly reduced the incidence of CV and improved functional outcomes in patients with aSAH compared to Oz+Fs."

Journal • Cardiovascular • Hematological Disorders • Subarachnoid Hemorrhage

Clazosentan-induced reversible focal brain edema in basal ganglia following aneurysmal subarachnoid hemorrhage treatment: illustrative case. (PubMed, J Neurosurg Case Lessons) - "Clazosentan can cause reversible localized vasogenic brain edema in the basal ganglia following subarachnoid hemorrhage treatment. This rare but significant complication underscores the importance of careful neurological monitoring and timely imaging in patients receiving clazosentan. Further research is required to understand the risk factors and mechanisms underlying this phenomenon. https://thejns.org/doi/10.3171/CASE24567."

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

Preventing Fluid Retention After Subarachnoid Haemorrhage During Administration of Endothelin Receptor Antagonist. (PubMed, Adv Exp Med Biol) - "Prevention of delayed cerebral infarction (DCI) due to cerebral vasospasm after subarachnoid haemorrhage (SAH) has been done with intravenous Rho kinase inhibitors (ROCKI), ozagrel sodium (TXA2I), selective ROCKI infusion (ROCKI i.a.), and cerebrospinal fluid (CSF) drainage. The endothelin receptor antagonist (ERA, clazosentan) became available in 2022 and is said to be highly recommended for DCI prevention, while fluid retention such as pleural effusion and pulmonary oedema accumulation is often experienced...We examined the results of blood sampling on admission, echocardiography, chest computed tomography (CT), with postoperative DCI, and hydrocephalus requiring cerebrospinal fluid shunt (hydro), and symptomatic fluid retention requiring albumin and furosemide (third fluid space)...Our experience suggests that age may be the most influential factor. Based on these results, we have also found that by avoiding the use of ERA in patients older than 80 years,..."

Journal • Cardiomyopathy • Cardiovascular • CNS Disorders • Congestive Heart Failure • Heart Failure • Respiratory Diseases • Subarachnoid Hemorrhage • Ventriculomegaly • NPPB

Symptomatic Vasospasm Refractory to Clazosentan after Subarachnoid Hemorrhage of Ruptured Vertebral Artery Dissecting Aneurysm: Clinical Implications from Two Contrasting Cases. (PubMed, Medicina (Kaunas)) - "These results imply the limited effectiveness of clazosentan in cases of thick and diffuse SAH after a ruptured VADA, even in good-clinical-grade patients treated with less invasive modalities. The HU values may become a simple quantitative marker for predicting symptomatic vasospasms and chronic hydrocephalus."

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

Postoperative Management of Aneurysmal Subarachnoid Hemorrhage (PubMed, No Shinkei Geka) - "In Japan, fasudil hydrochloride and ozagrel sodium are widely used to prevent vasospasms; however, their effects are sometimes insufficient. This was demonstrated in a recent randomized phase 3 trial, leading to the approval of clazosentan by the Pharmaceuticals and Medical Devices Agency in Japan. Recent advances in our understanding of subarachnoid hemorrhage will facilitate improved management to reduce the incidence of DCI."

Journal • Review • Cardiovascular • Hematological Disorders • Subarachnoid Hemorrhage

Successful administration of clazosentan in subarachnoid hemorrhage patient with severe heart failure. (PubMed, Surg Neurol Int) - "Neither cerebral vasospasm nor cardiopulmonary complications were observed. This case highlights the importance of a multidisciplinary approach in managing complex patients with severe cardiac comorbidities undergoing clazosentan therapy."

Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders • Respiratory Diseases • Subarachnoid Hemorrhage

Letter to the editor: "Beyond nimodipine: advanced neuroprotection strategies for aneurysmal subarachnoid hemorrhage vasospasm and delayed cerebral ischemia". (PubMed, Neurosurg Rev) - "It highlights the pharmacological advantages of nicardipine, cilostazol, and clazosentan over nimodipine in managing cerebral vasospasm and delayed cerebral ischemia. Emphasizing the need for personalized medicine, it advocates for integrating genetic screening and advanced monitoring techniques to tailor treatments to individual patient profiles. This approach could significantly improve clinical outcomes by optimizing drug efficacy and minimizing adverse effects."

Journal • Metastases • Cardiovascular • Hematological Disorders • Subarachnoid Hemorrhage

REACT: a randomized trial to assess the efficacy and safety of clazosentan for preventing clinical deterioration due to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. (PubMed, J Neurosurg) - P3 | "Clazosentan administered for up to 14 days at 15 mg/hour had no significant effect on the occurrence of clinical deterioration due to DCI. Clinical trial registration no.: NCT03585270 (ClinicalTrials.gov) EU clinical trial registration no.: 2018-000241-39 (clinicaltrialsregister.eu)."

Clinical • Journal • Cardiovascular • CNS Disorders • Hematological Disorders • Subarachnoid Hemorrhage • Vascular Neurology

Letter to editor: Beyond nimodipine: advanced neuroprotection strategies for aneurysmal subarachnoid hemorrhage vasospasm and delayed cerebral ischemia. (PubMed, Neurosurg Rev) - "This critique discusses neuroprotective strategies for aneurysmal subarachnoid hemorrhage (SAH), excluding Nimodipine, emphasizing alternatives like verapamil, albumin, and cilostazol. The letter underscores the need for comprehensive safety assessments and long-term outcome studies to enhance practical application. Highlighting ongoing trials and emerging therapies like clazosentan and TAK-044, it advocates for future research directions focused on large-scale RCTs and combination therapies, such as cilostazol and Nimodipine, which have demonstrated synergistic benefits in reducing delayed cerebral ischemia (DCI) and improving patient outcomes."

Journal • Metastases • Cardiovascular • Hematological Disorders • Subarachnoid Hemorrhage

Beyond nimodipine: advanced neuroprotection strategies for aneurysmal subarachnoid hemorrhage vasospasm and delayed cerebral ischemia. (PubMed, Neurosurg Rev) - "Eicosapentaenoic acid, dapsone and clazosentan showed a good balance between effectiveness and favorable pharmacokinetics...Nicardipine, cilostazol, Rho-kinase inhibitors, and clazosentan proved their better pharmacokinetic profiles compared with nimodipine without prejudice with effective and safe neuroprotective role. However, the number of trials conducted is significantly lower than for nimodipine. Aneurysmal SAH-associated vasospasm remains an area of ongoing preclinical and clinical research where the search for new drugs or associations is critical."

Journal • Metastases • Review • Cardiovascular • Hematological Disorders • Subarachnoid Hemorrhage

The effectiveness and safety of clazosentan in treating aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis. (PubMed, J Clin Neurosci) - "Clazosentan demonstrates efficacy in reducing vasospasm, moderate to severe vasospasm, DCI, and the need for rescue therapy in aSAH patients, but does not significantly improve functional outcomes or mortality rates. While associated with specific adverse events, clazosentan may be a valuable adjunctive therapy in the management of aSAH, particularly in a high-risk population for vasospasm."

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

Prophylactic management of cerebral vasospasm with clazosentan in real clinical practice: a single-center retrospective cohort study. (PubMed, Front Neurol) - "After clazosentan was approved for use in Japan, the conventional postoperative management protocol, composed of intravenous fasudil chloride and oral cilostazol (control group, April 2021 to March 2022), was changed to the clazosentan protocol (clazosentan group, April 2022 to March 2023). A postoperative management protocol centering on clazosentan was associated with the reduced vasospasm-related symptomatic infarction and improved clinical outcomes compared to the conventional management protocol in Japanese clinical practice. Clazosentan might be a promising treatment option for counteracting cerebral vasospasm after aneurysmal SAH."

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

Comparison of efficacy between clazosentan and fasudil hydrochloride-based management of vasospasm after subarachnoid hemorrhage focusing on older and WFNS grade V patients: a single-center experience in Japan. (PubMed, Neurosurg Rev) - "Clazosentan was more effective than fasudil-based management in preventing DCI and reducing vasospasm-related M/M. Clazosentan could be used safely in older patients and those with WFNS grade V, although clinical outcomes in these patients were comparable to those of conventional treatment."

Journal • Cardiovascular • Hematological Disorders • Subarachnoid Hemorrhage

Factors Influencing Discontinuation of Clazosentan Therapy in Elderly Patients with Aneurysmal Subarachnoid Hemorrhage: A Retrospective Study from a Japanese Single Center. (PubMed, Med Sci Monit) - "CONCLUSIONS Our results suggest that approximately 20% of SAH patients suffered from intolerable respiratory symptoms attributable to hypoxemia. We found that both reduced day-to-day urine volume variation and older age are independent risk factors for drug discontinuation."

Journal • Retrospective data • Cardiovascular • Hematological Disorders • Ischemic stroke • Pulmonary Disease • Subarachnoid Hemorrhage