Comparison Of Efficacy Of Levosimendan Versus Milrinone In Catecholamine Resistant Septic Shock With Myocardial Dysfunction In Children : A Single-Center, Open-Label Randomized controlled Trial - Nil

开始日期2025-03-31

申办/合作机构-

NCT06478667

/ Not yet recruiting临床3期IIT

The Role of Levosimendan As Inotropic Agent in Acute Aluminum Phosphide-induced Cardiotoxicity: a Randomized Controlled Trial

To evaluate the potential role of levosimendan as an inotropic agent in aluminum phosphide-induced cardiotoxicity

开始日期2024-12-01

申办/合作机构

Ain Shams University

ChiCTR2400091067

/ SuspendedN/AIIT

Clinical analysis of Levosimendan associated arrhythmia in Heart Failure patients

开始日期2024-10-21

申办/合作机构-

100 项与左西孟旦相关的临床结果

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100 项与左西孟旦相关的转化医学

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100 项与左西孟旦相关的专利（医药）

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2,187

项与左西孟旦相关的文献（医药）

2025-06-01·TOXICOLOGY

Mice mortality induced by dexmedetomidine is non-alpha2-adrenergic receptor-dependent

Article

作者: Li, Yulei ; Wang, Jiaqi ; Su, Ruibin ; Wang, Xiaoxuan ; Yin, Jiye ; Zhou, Peilan

Dexmedetomidine (DMED) is widely used in sedative anesthetics in clinical settings. Currently, there are no therapeutic interventions available for the lethal toxicity induced by DMED. Administered at doses ranging from 25 to 100 mg/kg intraperitoneally (i.p.), DMED exhibited a dose-dependent fatality in mice. The 50 % lethal dose (LD50) was determined to be 48.5 mg/kg within 24 h and 44.8 mg/kg within 7 days. Alpha2-adrenergic receptor antagonists, namely yohimbine and atipamezole, demonstrated no mitigating effect on the lethal toxicity induced by DMED at the dose of 44.8 mg/kg. Conversely, the administration of atipamezole and yohimbine increased the mortality associated with DMED. By contrast, the imidazoline receptor antagonist idazoxan and the opioid receptor antagonist naloxone significantly attenuated the mortality induced by DMED, thereby prolonging the median survival time following administration of DMED at 44.8 mg/kg (i.p.). Furthermore, the immune modulator imiquimod, calcium sensitizer levosimendan, and TAAR1 antagonist RO5212773 decreased acute mortality without impacting chronic mortality induced by DMED. Histopathological analysis revealed characteristic lung alterations, including capillary hemorrhage, widened alveolar septa, fusion of pulmonary alveoli, and inflammatory cell infiltrate upon DMED exposure. Pretreatment with idazoxan or naloxone inhibited these pathological changes induced by DMED, while atipamezole or yohimbine pretreatment exacerbated lung damage. Elevated levels of serum creatine kinase and myoglobin were noted following DMED administration. However, pretreatment with idazoxan or naloxone decreased the rise of serum creatine kinase and myoglobin. Collectively, these results highlighted the involvement of imidazoline receptors and opioid receptor in DMED mortality.

2025-06-01·SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY

A chemoinformatics study to prioritization of anticancer orally active lead compounds of pearl millet against adhesion G protein-coupled receptor

Article

作者: Shukla, Adarsh Kumar ; Neeru ; Kumar, Ashwani

Metastasis is the main cause of colon cancer deaths worldwide. However, due to the disease's complexity, understanding its spread and finding natural treatments remain major challenges. The study aimed to identify therapeutic compounds in pearl millet and test them on metastatic colon cancer cell lines. The study used LC-MS and FTIR spectroscopy to identify small compounds and their functional groups. Further, theoretical chemistry, computational techniques, and ADMET analysis were applied for virtual screening and evaluating the pharmacokinetics of potential bioactive candidates of pearl millet. The 55 compounds of pearl millet were identified through the LC-MS, whereas 37 compounds were reported in PubChem database. Out of these, 15 compounds were predicted as potential orally active leads of pearl millet. Adhesion G protein-coupled receptor F5 was found as a potential target of these lead candidates. Further, molecular docking exhibited Tosifen (-7.9 kcal/mol), Sufentanil (-6.4 kcal/mol), Pemirolast (-6.3 kcal/mol), and Levosimendan (-6.3 kcal/mol) have similar binding affinity to the antineoplastics against the targeted protein. The "root mean square fluctuations (RMSFs)" analysis and deformability graph validated the docked complexes. Additionally, a comparative cell lines study against colon adenocarcinoma highlights Pemirolast as a promising candidate, demonstrating better activity compared to standard antineoplastics. This computational study predicted potential anticancer compounds in pearl millet and recommended further investigation through in vitro and in vivo studies.

2025-05-01·Current Vascular Pharmacology

The Early Pharmacological Strategy with Inodilator, bEta-blockers, Mineralocorticoid Receptor Antagonists, Sodium-glucose coTransporter-2 Inhibitors and Angiotensin Receptor-neprylisin Inhibitors in Acute Heart Failure (PENTA-HF)

Article

作者: D'Amato, Andrea ; Maestrini, Viviana ; Mariani, Marco Valerio ; Prosperi, Silvia ; Severino, Paolo ; Vizza, Carmine Dario ; Labbro Francia, Aurora ; Cestiè, Claudia ; Filomena, Domenico ; Fedele, Francesco ; Marek-Iannucci, Stefanie ; Myftari, Vincenzo ; Manzi, Giovanna ; Mancone, Massimo ; Badagliacca, Roberto

Purpose::

The management of acute heart failure (AHF) is crucial and challenging. Regarding the use of inotropes, correct patient selection and time of administration are of the essence. We hypothesize that the early use of Levosimendan favouring hemodynamic stabilization and enables rapid optimization of guideline-directed medical therapy (GDMT) in patients with HF, eventually impacting the patient’s prognosis during the vulnerable phase.

Methods::

This prospective, observational study enrolled consecutive patients admitted due to AHF. Propensity score matching (PSM) analysis has been used to homogenize differences between groups. In group 1 (G1), patients were treated with early 24-h Levosimendan infusion followed by in-hospital introduction/up-titration of GDMT. In group 2 (G2), patients were treated with alternative inotropes/ vasopressors followed by in-hospital introduction/up-titration of GDMT. The comparison between the two groups has been performed at the 6-month follow-up in terms of cardiovascular (CV) mortality and HF hospitalizations (HFH).

Results::

233 patients were included in the present study, and after propensity match adjustments, 176 patients were analysed, 88 patients for each group. No differences in the baseline characteristics have been reported between the groups. At 6 months follow-up, no statistically significant differences were shown in terms of the composite endpoint of CV death and HFH (p = 0.445) and CV death (p = 0.62). Statistically significant differences between the two groups were reported in terms of HFH (p = 0.02). The Kaplan-Meier survival analysis showed that patients in G1 were significantly less hospitalized compared to G2 during the 6 months after the index hospitalization (log-rank p = 0.03).

Conclusions::

Early 24-hour infusion of Levosimendan followed by rapid optimization of HF diseasemodifying therapies results in a significant reduction of HFH in the vulnerable post-discharge phase.

111

项与左西孟旦相关的新闻（医药）

2025-04-17

·PRNewswire

TRYVIO/JERAYGO Positioned to Redefine Treatment of Resistant Hypertension | DelveInsight

TRYVIO (aprocitentan) in the US and JERAYGO in Europe present significant market potential as novel therapies for patients with hypertension inadequately controlled by existing treatments. TRYVIO, approved by the FDA in March 2024 and commercially available since October 2024, targets systemic hypertension in adults not adequately controlled on other drugs. LAS VEGAS, April 17, 2025 /PRNewswire/ -- DelveInsight's " TRYVIO/JERAYGO Market Size, Forecast, and Market Insight Report" highlights the details around TRYVIO/JERAYGO, a dual endothelin receptor antagonist. The report provides product descriptions, patent details, and competitor products (marketed and emerging therapies) of TRYVIO/JERAYGO. The report also highlights the historical and forecasted sales from 2020 to 2034 segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan]. Idorsia Pharmaceuticals' TRYVIO/JERAYGO (aprocitentan) Overview TRYVIO is a once-daily oral medication that acts as a dual endothelin receptor antagonist, blocking the binding of endothelin-1 (ET-1) to both ETA and ETB receptors. This mechanism makes it particularly effective for reducing blood pressure in adults whose hypertension remains uncontrolled with other treatments. TRYVIO also has a low risk of drug-drug interactions. The active ingredient, aprocitentan, is marketed as TRYVIO in the United States, while in the European Union and the UK, it is available under the brand name JERAYGO. Marketing applications are currently under review in Canada and Switzerland. Notably, TRYVIO is the first oral antihypertensive in a new therapeutic class to receive approval in nearly four decades. Learn more about TRYVIO/JERAYGO projected market size for resistant hypertension @ TRYVIO/JERAYGO Market Potential Resistant hypertension is defined as blood pressure that remains above target levels despite the concurrent use of three antihypertensive agents of different classes, ideally including a diuretic, at optimal doses. This condition affects approximately 10-20% of the hypertensive population and is associated with a higher risk of cardiovascular events, stroke, and renal complications. The pathophysiology is often multifactorial, involving factors such as obesity, high salt intake, secondary hypertension causes, and medication nonadherence. Managing resistant hypertension is challenging due to its complex etiology, requiring a more personalized and multidisciplinary approach. The current treatment paradigm includes intensifying lifestyle interventions, ensuring optimal diuretic use, and exploring secondary causes. In recent years, device-based therapies such as renal denervation and baroreceptor activation therapy have emerged as potential options for select patients, although uptake has been cautious due to mixed clinical trial results. Pharmaceutical innovation has been relatively limited, but there is renewed interest in novel drug classes such as aldosterone synthase inhibitors, endothelin receptor antagonists, and dual-acting agents. The future market outlook is positive, driven by an aging global population, increasing prevalence of obesity and diabetes, and heightened awareness of cardiovascular risk. We expect the resistant hypertension market to grow steadily, with significant commercial opportunity for both drug developers and medtech innovators offering targeted, evidence-based solutions. Discover more about the resistant hypertension market in detail @ Resistant Hypertension Market Report Emerging Competitors of TRYVIO/JERAYGO Some of the competing emerging key players include AstraZeneca (Baxdrostat), Mineralys Therapeutics (Lorundrostat), Tenax Therapeutics (TNX-103), and others. In March 2025, Tenax Therapeutics, Inc. announced that the FDA had completed its review of the company's revised Phase 3 development strategy for TNX-103 (oral levosimendan). This included approval of an amendment to expand patient enrollment and enhance the statistical power of the ongoing Phase III LEVEL trial, as well as the protocol for LEVEL-2, Tenax's second registrational Phase III study. The company stated that it now plans to enroll 230 patients in the LEVEL study, boosting the study's statistical power to over 95%. LEVEL-2, a global trial, is expected to launch in 2025. In March 2025, Mineralys Therapeutics, Inc. reported comprehensive results from the Phase II Advance-HTN trial, one of two key studies assessing lorundrostat in patients with confirmed uncontrolled hypertension (uHTN) or resistant hypertension (rHTN). In this trial, the 50 mg dose of lorundrostat achieved an absolute reduction of 15.4 mmHg in blood pressure and a placebo-adjusted reduction of 7.9 mmHg at week 12. The treatment also showed a favorable safety and tolerability profile, with only minor changes observed in potassium, sodium, and eGFR levels, and a low rate of treatment discontinuation. To know more about the number of competing drugs in development, visit @ TRYVIO/JERAYGO Market Positioning Compared to Other Drugs Key Milestones of TRYVIO/JERAYGO In March 2025, Idorsia announced that the US FDA had fully released TRYVIO from its REMS (Risk Evaluation and Mitigation Strategy) requirement. Idorsia is also released from the post-marketing requirement (PMR) to conduct a worldwide descriptive study that collects prospective and retrospective data in women exposed to TRYVIO during pregnancy and/or lactation, as these data are no longer needed. Idorsia no longer has post-marketing requirements for TRYVIO. In January 2025, Medicines and Healthcare Products Regulatory Agency (MHRA) approved JERAYGO to treat hypertension (high blood pressure) in adults whose blood pressure cannot be adequately controlled by at least three other medicines (also known as resistant hypertension), in the UK. In July 2024, Idorsia received approval from the European Commission for JERAYGO for the treatment of resistant hypertension in adult patients in combination with at least three antihypertensive medicinal products. The recommended dose is 12.5 mg orally once daily. The dose can be increased to 25 mg once daily for patients tolerating the 12.5 mg dose and in need of tighter blood pressure control. In March 2024, Idorsia announced that the US Food and Drug Administration (FDA) has approved TRYVIO for the treatment of hypertension in combination with other antihypertensive drugs to lower blood pressure in adult patients who are not adequately controlled on other drugs. The recommended dosage of TRYVIO is 12.5 mg orally once daily, with or without food. It was made commercially available in the US in October 2024. Discover how TRYVIO/JERAYGO is shaping the resistant hypertension treatment landscape @ TRYVIO/JERAYGO Medication TRYVIO/JERAYGO Market Dynamics TRYVIO (also marketed as JERAYGO in select markets) is a promising therapeutic entrant in the treatment landscape for resistant hypertension, representing a novel mechanism of action targeting the aldosterone pathway. As a selective aldosterone synthase inhibitor, TRYVIO addresses a key pathophysiological driver in resistant hypertension—aldosterone excess—offering a more targeted approach compared to traditional mineralocorticoid receptor antagonists (MRAs) like spironolactone or eplerenone. This differentiation positions TRYVIO as an important alternative for patients who are intolerant to MRAs or who do not achieve adequate blood pressure control despite existing therapies. TRYVIO's entry comes at a time when the hypertension market is seeing renewed attention toward personalized, mechanism-based treatments. Early clinical trial data have demonstrated meaningful reductions in systolic blood pressure with a favorable safety and tolerability profile. This has led to increasing interest among specialists in cardiology and nephrology. TRYVIO's potential to be used alongside existing antihypertensive agents without significant drug-drug interactions is a key advantage. However, uptake may be moderated in the short term by p hysician familiarity with MRAs, payer scrutiny on pricing, and the need for broader real-world data to confirm long-term efficacy and safety. From a regulatory standpoint, TRYVIO/JERAYGO has gained approvals in several major markets, including the U.S. and EU, with regulatory filings underway in Asia-Pacific regions. Payers are cautiously optimistic, with reimbursement being granted in many geographies based on unmet needs and pharmacoeconomic models projecting reductions in cardiovascular events and hospitalizations. That said, its premium pricing compared to generics necessitates the generation of robust health economic data to support its value proposition, especially in cost-sensitive healthcare systems. Looking ahead, TRYVIO is well-positioned to capture a substantial share of the resistant hypertension market, particularly as guidelines begin to incorporate newer therapeutic classes. We forecast steady growth driven by expanding physician adoption, increasing diagnosis of resistant hypertension, and potential label expansion into related indications such as heart failure with preserved ejection fraction (HFpEF). Strategic partnerships, post-marketing surveillance, and long-term outcome studies will be critical in shaping TRYVIO's competitive edge and sustaining momentum in a crowded but evolving treatment landscape. Dive deeper to get more insight into TRYVIO/JERAYGO's strengths & weaknesses relative to competitors @ TRYVIO/JERAYGO Market Drug Report Table of Contents Related Reports Resistant Hypertension Pipeline Resistant Hypertension Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key resistant hypertension companies, including Idorsia Ltd, Janssen Biotech, Quantum Genomics SA, CinCor Pharma, Ionis Pharmaceuticals, and Vifor Pharma, among others. Hypertension Market Hypertension Market Insight, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of market trends, market drivers, market barriers, and key hypertension companies such as Mineralys Therapeutics Inc., CinCor Pharma, among others. Hypertension Pipeline Hypertension Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key hypertension companies, including Gossamer Bio, Addpharma Inc., Insmed Incorporated, Alnylam Pharmaceuticals, 35Pharma Inc, Pfizer, Pharmosa Biopharm Inc., Guangzhou Magpie Pharmaceuticals Co., Ltd., Suzhou Sanegene Bio Inc., JW Pharmaceutical, among others. Treatment-Resistant Hypertension Market Treatment-Resistant Hypertension Market Insight, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of market trends, market drivers, market barriers, and key TRD companies such as Ionis Pharmaceuticals, KBP Biosciences, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床结果上市批准临床3期临床2期

2025-04-16

·梅斯医学

惊心！5 岁娃感冒后突发抽搐，背后竟藏致命危机

广东佛山顺德地区，5 岁的男孩康康（化名）身体突感不适，出现了腿疼、发热、流鼻涕以及咳嗽等症状。心急如焚的家长赶忙带着康康前往医院就诊。然而，仅仅过了两天，病情就如同脱缰野马般急转直下。在住院治疗期间，康康突然发生抽搐，情况十分危急。医生迅速对其进行全面检查，结果显示，康康的心肌酶指标显著升高，还伴随心律失常。经过一系列检查，最终，康康被确诊为暴发性心肌炎。幸运的是，在医院儿童重症医学科及多学科的合作下，通过体外膜肺氧合（ECMO）4天治疗后，康康转危为安。看似感冒表象下，暴发性心肌炎已悄然潜伏儿童暴发性心肌炎，是一种极其棘手且来势汹汹的疾病，其本质上是心肌发生的炎症，并且进展速度极为迅速。一旦发病，心肌会在短时间内遭受严重的炎症侵袭，进而导致心功能急剧受损。心功能受损可不是小事，心脏原本肩负着向全身各个器官输送血液的重任，而此时，它却难以正常履职，心脏无法有力地泵血，就会引发心源性休克。那么，从急性心肌炎（AM）发展为暴发性心肌炎，是否存在危险信号预警？急性心肌炎（AM）转变成暴发性心肌炎的危险信号则为乏力、胸闷、胸痛、呼吸困难等症状的快速发作以及QRS波振幅下降、严重的传导阻滞、恶性心律失常、心功能降低等。暴发性心肌炎的病因包括感染因素和非感染因素，感染因素中，病毒感染是主要的病因，非感染性因素包括自体免疫、过敏、药物和毒性反应等。精准锁定！儿童暴发性心肌炎诊断密钥儿童暴发性心肌炎的诊断一直是备受关注且极具挑战性的重要课题。那么，究竟该如何准确诊断儿童暴发性心肌炎呢？美国心脏协会、欧洲心脏病学会及日本循环协会均将出现心源性休克的 AM 定义为暴发性心肌炎，但这些指南、共识及科学声明均没有对儿童暴发性心肌炎提出明确的诊断标准，且对儿童暴发性心肌炎的治疗没有系统阐述。不过，通过长期的临床实践与研究积累，目前已形成了一套较为通用的儿童暴发性心肌炎临床诊断依据。儿童暴发性心肌炎的临床诊断依据如下：（1）急骤起病，进展迅速，起病前数日或2~4周内可有前驱感染症状、自身免疫性疾病、药物应用或毒性物质接触。（2）病情危重，突发心源性休克、心力衰竭、心源性猝死，需正性肌力治疗和（或）机械循环支持，可伴有多系统衰竭。（3）肌钙蛋白I或T、高敏肌钙蛋白I或T、肌酸激酶同工酶MB、B型利钠肽（BNP）或 N 末端 B 型利钠肽原（NT‑proBNP）可出现异常增高。（4）心电图呈现多样性改变，包括各种类型心律失常、低电压、T波及ST段改变。（5）超声心动图：室间隔或心室壁稍增厚（心肌水肿所致），弥漫性室壁运动减低或节段性室壁运动异常，左心室收缩功能减低。当患儿有前驱症状与体征，同时出现低血压和（或）心源性休克时，临床医生便会高度怀疑暴发性心肌炎的可能。而如果患儿同时符合以上所提及的 5 条诊断依据，那么即可在临床上明确诊断为暴发性心肌炎。攻克难题：儿童暴发性心肌炎治疗方案全总结大多数暴发性心肌炎患儿度过急性期后可痊愈，个别病例在随访过程中出现左心室功能受损。影响预后的主要因素包括年龄、心肌受损的严重程度、组织学亚型及治疗是否及时、早期是否充分休息。暴发性心肌炎的救治依靠 MDT 团队的密切协作，以生命支持治疗为中心的综合救治方案。一般支持治疗：暴发性心肌炎患儿应卧床休息、防止躁动或剧烈哭吵，必要时用镇静剂，采用卧位或半卧位以减轻心脏负担。供给湿化氧，当患儿呼吸急促、呼吸困难不易纠正时应及早给予呼吸支持，可以采用持续气道正压通气或有创呼吸机辅助通气。控制液体出入量，纠正电解质紊乱及酸中毒。心肌能量代谢药物用于改善心肌细胞能量代谢，常选用 1，6‑二磷酸果糖、辅酶Q10、左卡尼汀、磷酸肌酸钠等。重症监护：暴发性心肌炎患儿应转运至有呼吸循环监护和支持治疗条件的重症监护病房密切监护。监护内容主要包括心电、血压、氧饱和度和出入量监测；血液学指标监测；超声心动图动态监测；有创血流动力学监测。心源性休克治疗：包括液体治疗，心肺复苏术，血管活性药物及磷酸二酯酶抑制剂和钙增敏剂。具体而言，暴发性心肌炎所致休克主要是由于心肌收缩功能障碍而导致的心源性休克。因此，在抗休克治疗中，正性肌力药物至关重要。液体治疗以限制液体量为主，避免盲目扩容而诱发或加重急性左心衰竭和肺水肿，液体输注速度宜缓慢匀速，避免短时快速输注液体。对心率、血压显著下降者，应行有效的心肺复苏术。此外，合理选用血管活性药物。当暴发性心肌炎患儿合并心源性休克，且血压难以维持在正常水平时，可酌情选用儿茶酚胺类药物。值得注意的是，在患儿血压恢复稳定，组织灌注得到有效改善后，应尽早逐步减量并停用此类药物，避免药物长期使用带来的不良影响。磷酸二酯酶抑制剂兼具增强心肌收缩力以及扩张血管平滑肌的双重功效。然而，在暴发性心肌炎急性期，患儿循环状态极不稳定，此时需谨慎使用该类药物。钙增敏剂左西孟旦，能够与心肌肌钙蛋白 C 紧密结合，从而发挥正性肌力作用，且不会对心室舒张功能造成不良影响。心力衰竭的治疗：在循环血容量充足和血压稳定的前提下，患有心力衰竭的儿童暴发性心肌炎可根据具体情况选用洋地黄类药物、血管扩张剂和利尿剂。洋地黄类药物主要用于FM恢复期出现心肌收缩功能障碍的患儿，地高辛口服时建议使用维持量（常规剂量的1/2），避免快速饱和以防中毒；西地兰适用于严重心力衰竭或无法口服药物的患儿，首剂为洋地黄化量的1/3~1/2，余量分次给予，维持量为洋地黄化量的1/5，但合并三度房室传导阻滞、窦性心动过缓或室性心律失常者禁用。血管扩张剂一般不推荐用于FM患儿，但在ECMO等生命支持期间合并高血压、急性肺水肿或充血性心力衰竭时可谨慎使用，需从小剂量开始并监测血压。利尿剂可用于改善水钠潴留，减轻心脏前负荷和脏器充血，尤其适用于急性左心衰竭合并肺水肿的患儿，但在心源性休克时需慎重使用。心律失常治疗：在心律失常的治疗中，针对不同类型的严重心律失常采取相应措施：对于三度房室传导阻滞，需在给予静脉注射免疫球蛋白（IVIG）及甲泼尼龙的同时，紧急安装心脏临时起搏器以维持心脏节律；对于持续室性心动过速，可选择静脉给予利多卡因或胺碘酮，具体用法用量需遵循医嘱并注意相关注意事项；对于室上性心动过速，可给予胺碘酮进行治疗。机械循环辅助治疗：机械循环辅助治疗是针对严重心力衰竭的重要手段，其中体外膜氧合（ECMO）适用于心脏功能极差（如心脏指数<2.0 L/（min·m²）、左心室射血分数<40%等）、持续性组织低灌注、持续性低血压、多种血管活性药物无效、严重心律失常或心脏停搏等情况，且任意一条不稳定持续3小时需快速启动ECMO。ECMO撤机指征包括左心室射血分数>40%、脉压和混合静脉血氧饱和度恢复正常，或在出现严重并发症前撤机或更换器械，辅助时间超过12.5天需考虑更换器械或进行心脏移植。ECMO的并发症包括神经系统功能障碍、肾功能衰竭、下肢缺血、脓毒症、出血等。此外，主动脉内球囊反搏（IABP）适用于5岁以上且仅有左心室功能不良的患儿，而心室辅助装置（VAD）则推荐用于长期ECMO撤机困难或等待心脏移植的患儿。血液净化及连续肾脏替代治疗：连续血液净化（CBP）是一种重要的治疗手段，适用于多种严重电解质紊乱和代谢异常的情况，其适应症包括严重的高血钾（血清钾>6.5 mmol/L）、严重的高血钠或低血钠（血清钠>160 mmol/L或<115 mmol/L）、难以纠正的酸中毒（血pH<7.1或碳酸氢根<12 mmol/L）、严重的液体超负荷，以及合并急性肾损伤（血尿素氮>30 mmol/L）、急性肝衰竭、药物治疗无效的肺水肿和顽固性心力衰竭等情况。对于这些危及生命的状况，应快速启动CBP以稳定患者的内环境，改善预后。免疫治疗：免疫治疗包括免疫调节和免疫抑制两种方式。在免疫调节方面，静脉注射免疫球蛋白（IVIG）的总剂量为2 g/kg，可选择1 g/（kg·d）连续使用2天；对于严重心功能不全的患者，可采用400或500 mg/（kg·d）连续使用4或5天。在免疫抑制方面，糖皮质激素（如甲泼尼龙）可用于冲击治疗，剂量为10~30 mg/（kg·d），连续应用3~5天后减量至2 mg/（kg·d），病情稳定后改为泼尼松口服1.0~2.0 mg/（kg·d），疗程2~4周，随后根据患儿的症状、炎症因子水平、心肌酶和心功能指标逐渐减量，通常在1~3个月内停药。参考资料中华医学会儿科学分会心血管学组，中国医师协会儿童重症医师分会心血管专业委员会，中国医师协会心血管内科医师分会儿童心血管专业委员会,等.儿童暴发性心肌炎诊治专家建议（2025）.中华儿科杂志，2025，63(04):351-361. DOI:10.3760/cma.j.cn112140-20241008-00702来源 | 梅斯医学综合整理编辑 | rayms授权转载及爆料请联络梅斯医学管理员点击下方“阅读原文” 下载梅斯医学APP吧！

2025-03-05

·drugs

Tenax Therapeutics Expands Phase 3 LEVEL Program, Advancing Two TNX-103 (Oral Levosimendan) Registrational Studies for the Treatment of PH-HFpEF

CHAPEL HILL, N.C., March 05, 2025 (GLOBE NEWSWIRE) -- Tenax Therapeutics, Inc. (Nasdaq: TENX) (“Tenax Therapeutics” or the “Company”), a Phase 3, development-stage pharmaceutical company using clinical insights to develop novel cardiopulmonary therapies, today announced the U.S. Food and Drug Administration (FDA) has completed their review of Tenax Therapeutics’ updated Phase 3 development plan for TNX-103 (oral levosimendan), including an Amendment to expand enrolment and increase the power of the ongoing Phase 3 LEVEL study, and the protocol for LEVEL-2, Tenax Therapeutics’ second registrational Phase 3 study. The Company today announced it expects to enroll 230 patients in the LEVEL study, increasing the statistical powering of the study to over 95%. LEVEL-2, a global study, is expected to commence in 2025. “We are increasing our investment in the clinical development plan for TNX-103 by expanding the ongoing LEVEL study and accelerating our plans to initiate the second registrational study, LEVEL-2. With the momentum provided from our $100 million financing in August 2024 and alignment with the FDA, we are now able to execute on our plan to advance these two Phase 3 registrational studies for TNX-103 in parallel. LEVEL is enrolling well: we are confident that, with more than 50 North American sites already activated, we can complete enrollment of this upsized study around year end, while also commencing the global LEVEL-2 study later this year,” said Chris Giordano, President and Chief Executive Officer of Tenax Therapeutics. “We expect these two registrational studies will satisfy the requirements, including the safety data expectations, to file in the U.S. and other geographies. We are funded well beyond our projected date for the release of topline LEVEL data, positioning us to advance the development of TNX-103 and improve the quality of life for patients living with PH-HFpEF.” LEVEL Study Expansion Enhances Statistical Power The LEVEL study, evaluating TNX-103 for the treatment of PH-HFpEF, will expand enrollment from 152 to at least 230 patients, increasing the statistical powering of the study. The Company is on track to enroll the first 150 subjects in the first half of 2025, expects to complete enrollment by around the end of 2025, and expects to present topline data from the LEVEL study in the middle of 2026. As of late February 2025, blinded LEVEL data reveal TNX-103 to be well-tolerated in patients with PH-HFpEF: Tenax Therapeutics’ Chief Medical Officer, Stuart Rich, MD, summarized: “In addition to high rates of study and therapy continuation, the adherence to the TID regimen has been high, and no new safety signals have been detected. About half the patients in the OLE have been on study for over 6 months, a few of them for more than a year, with very reassuring participation levels observed during the OLE.” LEVEL-2: A Global Registrational Trial Additionally, Tenax Therapeutics received input from the FDA on the protocol for the LEVEL-2 study, and expects this second, global registrational clinical trial to evaluate levosimendan in patients with PH-HFpEF to start enrolling this year, in several countries. The primary endpoint of 6MWD will be assessed at 26 weeks. Tenax intends to enroll a larger sample than LEVEL and evaluate patients for a full year of double-blind, placebo-controlled therapy, providing FDA and European reviewers a robust safety database for their benefit/risk assessments. “TNX-103 has the potential to meaningfully improve the quality of life of patients with PH-HFpEF, an underdiagnosed disease with significant unmet needs and no currently approved treatment options. I remain very hopeful that with positive Phase 3 results, these patients will finally have an approved treatment available,” said Dr. Rich. “We are continuing to work closely with the FDA, and are grateful for their input, which enables Tenax to accelerate development timelines of a potential first therapy for this devastating form of PH.” About the Phase 3 LEVEL Study ( NCT05983250 ) The LEVEL Study is a Phase 3, double-blind, randomized, placebo-controlled study of oral levosimendan in patients with PH-HFpEF. Approximately 230 subjects will be randomized in a 1:1 ratio to receive an oral dose of levosimendan (2 mg/day) or placebo for Weeks 1 to 4 and 3 mg/day or placebo for Weeks 5 to 12. The primary outcome measure for the study is change in six-minute walk distance from Baseline to Week 12. All randomized subjects will have the option to enter the 92-week OLE following the completion of all study endpoints at Week 12. About the Phase 3 LEVEL-2 Study LEVEL-2 is a global Phase 3, double-blind, randomized, placebo-controlled study of oral levosimendan in patients with PH-HFpEF. Patients will be randomized to receive an oral dose of levosimendan (2mg/day) or placebo for Weeks 1 to 4 and 3mg/day or placebo from Week 5 onward. The primary endpoint of 6MWD will be assessed at 26 weeks. About Levosimendan (TNX-101, TNX-102, TNX-103) Levosimendan is a unique, potassium ATP channel activator and calcium sensitizer that affects the heart and vascular system through multiple mechanisms of action, and that is being developed as an oral therapy (TNX-103) for pulmonary hypertension (PH) with heart failure with preserved ejection fraction (PH-HFpEF). Initially discovered and developed by Orion Corporation in Finland, intravenous levosimendan has been granted market authorization in 60 countries outside the United States for use in hospitalized patients with acutely decompensated heart failure. Results of Tenax Therapeutics’ Phase 2 HELP study of levosimendan in patients with HFpEF demonstrated that IV levosimendan (TNX-101) produces potent dilation of the central and pulmonary venous circulations which translates into an improvement in exercise capacity, a discovery that is the basis of LEVEL, the Phase 3 investigation of Tenax Therapeutics’ potential groundbreaking therapy. To date, no other drug therapy has demonstrated improved exercise tolerance in patients with PH associated with HFpEF, “a growing epidemic with high morbidity and mortality and no treatment. The clear unmet need and lethal nature of PH-HFpEF must be met with novel solutions at all levels of therapeutic development” (AHA Scientific Advisory, “A Call to Action,” 2022). About Tenax Therapeutics Tenax Therapeutics, Inc. is a Phase 3, development-stage pharmaceutical company using clinical insights to develop novel cardiopulmonary therapies. The Company owns global rights to develop and commercialize levosimendan, which it has prioritized. Tenax Therapeutics also may resume developing its unique oral formulation of imatinib. For more information, visit www.tenaxthera.com. Tenax Therapeutics’ common stock is listed on The Nasdaq Stock Market LLC under the symbol “TENX”. Caution Regarding Forward-Looking Statements Except for historical information, all of the statements, expectations and assumptions contained in this press release are forward-looking statements. These forward-looking statements may include information concerning possible or projected future business operations. Actual results might differ materially from those explicit or implicit in the forward-looking statements. Important factors that could cause actual results to differ materially include: risks of our clinical trials, including, but not limited to, the timing, delays, costs, design, initiation, enrollment, and results of such trials; any delays in regulatory review and approval of product candidates in development; risks related to our business strategy, including the prioritization and development of product candidates; reliance on third parties, including Orion Corporation, our manufacturers and CROs; risks regarding the formulation, production, marketing, customer acceptance and clinical utility of our product candidates; our estimates regarding the potential market opportunity for our product candidates; the potential advantages of our product candidates; risks associated with our cash needs; our ability to maintain our culture and recruit, integrate and retain qualified personnel and advisors, including on our Board of Directors; our competitive position; intellectual property risks; volatility and uncertainty in the global economy and financial markets in light of the possibility of pandemics, global financial and geopolitical uncertainties, including in the Middle East and the Russian invasion of and war against the country of Ukraine; changes in legal, regulatory and legislative environments in the markets in which we operate and the impact of these changes on our ability to obtain regulatory approval for our products; and other risks and uncertainties set forth from time to time in our SEC filings. Tenax Therapeutics assumes no obligation and does not intend to update these forward-looking statements except as required by law. Source: Tenax Therapeutics, Inc. Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

临床3期临床2期

100 项与左西孟旦相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D04720	左西孟旦	C01CX08	DB00922

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
心脏衰竭	阿根廷	AbbVie AS	2002-07-20
急性失代偿性心力衰竭	奥地利	Orion Oyj	2001-04-10
急性失代偿性心力衰竭	塞浦路斯	Orion Oyj	2001-04-10
急性失代偿性心力衰竭	芬兰	Orion Oyj	2001-04-10
急性失代偿性心力衰竭	希腊	Orion Oyj	2001-04-10
急性失代偿性心力衰竭	冰岛	Orion Oyj	2001-04-10
急性失代偿性心力衰竭	意大利	Orion Oyj	2001-04-10
急性失代偿性心力衰竭	挪威	Orion Oyj	2001-04-10
急性失代偿性心力衰竭	葡萄牙	Orion Oyj	2001-04-10
急性失代偿性心力衰竭	西班牙	Orion Oyj	2001-04-10
急性失代偿性心力衰竭	瑞典	Orion Oyj	2001-04-10

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
射血分数保留型心力衰竭	临床3期	美国	Medpace, Inc.	2024-01-10
射血分数保留型心力衰竭	临床3期	美国	Tenax Therapeutics, Inc.	2024-01-10
射血分数保留型心力衰竭	临床3期	加拿大	Medpace, Inc.	2024-01-10
射血分数保留型心力衰竭	临床3期	加拿大	Tenax Therapeutics, Inc.	2024-01-10
射血分数降低的心力衰竭	临床3期	美国	Medpace, Inc.	2024-01-10
射血分数降低的心力衰竭	临床3期	美国	Tenax Therapeutics, Inc.	2024-01-10
射血分数降低的心力衰竭	临床3期	加拿大	Medpace, Inc.	2024-01-10
射血分数降低的心力衰竭	临床3期	加拿大	Tenax Therapeutics, Inc.	2024-01-10
肺性高血压	临床3期	美国	Medpace, Inc.	2024-01-10
肺性高血压	临床3期	美国	Tenax Therapeutics, Inc.	2024-01-10

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ESC2024	N/A	心源性休克	349	Levosimendan + dobutamine	鬱簾簾艱顧醖淵願繭憲(餘簾獵遞鹹衊憲繭廠鏇) = 簾憲觸鬱選壓憲淵鏇顧壓鏇糧淵襯顧廠鑰網齋 (鏇願築齋簾選淵鹽鹹淵 )	积极	2024-09-02
				Dobutamine alone	鬱簾簾艱顧醖淵願繭憲(餘簾獵遞鹹衊憲繭廠鏇) = 齋積憲獵鏇壓蓋選選憲壓鏇糧淵襯顧廠鑰網齋 (鏇願築齋簾選淵鹽鹹淵 )
ESC2024	N/A	非ST段抬高型心肌梗死	-	Levosimendan	膚襯獵繭壓壓憲觸艱憲(範艱鹹鏇鑰夢鏇觸鬱鏇): aHR = 0.573 (95% CI, 0.466 ~ 0.704), P-Value = < 0.001 更多	-	2024-09-01
				Non-Levosimendan
NCT03541603 (HELP, CTgov)	临床2期	射血分数保留型心力衰竭 \| 继发性肺恶性肿瘤 \| 射血分数降低的心力衰竭 ... 更多	44	Levosimendan (Levosimendan 2.5mg/mL Injectable Solution)	窪觸衊窪製憲艱遞壓蓋(鹹獵蓋憲醖製範積願顧) = 膚艱願襯製壓鬱獵簾衊餘積顧鏇鬱廠鑰鬱餘壓 (製壓廠簾鑰淵鹽構觸鑰, 10.07) 更多	-	2024-05-14
				Matching Placebo (Matching Placebo)	窪觸衊窪製憲艱遞壓蓋(鹹獵蓋憲醖製範積願顧) = 餘鹽製醖襯構壓齋蓋遞餘積顧鏇鬱廠鑰鬱餘壓 (製壓廠簾鑰淵鹽構觸鑰, 7.87) 更多
ESC2024	N/A	-	-	Intermittent levosimendan infusion every 2 weeks	繭衊簾襯鏇鹹憲鹹簾壓(膚積簾製鏇蓋積艱積簾) = 製壓製蓋膚顧艱獵鹹衊衊鬱積襯糧築簾憲齋選 (構憲衊餘築構壓衊窪顧 ) 更多	-	2024-05-13
ESC2024	N/A	急性失代偿性心力衰竭 HFrEF \| LV \| OT ... 更多	58	levosimendan (Ischemic HFrEF)	積淵廠艱鹽齋選築憲觸(構製醖壓願衊願襯齋醖) = 構壓醖艱鏇餘鏇鏇網艱廠夢積築鬱鑰壓衊鏇範 (窪衊膚鹹構艱鹽簾餘鏇 ) 更多	积极	2024-05-13
				levosimendan (Non-ischemic HFrEF)	積淵廠艱鹽齋選築憲觸(構製醖壓願衊願襯齋醖) = 願艱築遞膚願齋餘壓窪廠夢積築鬱鑰壓衊鏇範 (窪衊膚鹹構艱鹽簾餘鏇 ) 更多
ESC2024	N/A	心脏衰竭	-	Levosimendan intermittent infusions	餘醖鏇選壓製鹽淵遞願(鑰獵壓遞憲製築選醖鏇) = 襯鏇憲簾夢繭獵衊襯鏇淵艱夢觸製鑰餘獵鬱繭 (網襯襯網艱顧餘鑰醖選, 8)	-	2024-05-13
ESC2024	N/A	心脏衰竭	-	Levosimendan	襯衊觸積網淵窪構網蓋(糧憲構積積積艱築鑰製) = 1 patient (3.8%) 範鹹襯壓網鑰醖齋製窪 (齋淵製糧醖憲鹹淵顧艱 ) 更多	-	2024-05-12
NCT02232399 (MiLe-1, CTgov)	临床2期	急性肾损伤 \| 先天性心脏缺损	72	Milrinone (Milrinone)	鏇齋衊積夢蓋餘獵構夢(窪顧淵鏇網觸膚餘觸顧) = 積憲鏇廠遞構繭鹽簾選構齋窪憲選構願鏇網獵 (鹽膚遞鹹鹽憲觸獵鏇鑰, 6.1) 更多	-	2024-03-26
				Levosimendan (Levosimendan)	鏇齋衊積夢蓋餘獵構夢(窪顧淵鏇網觸膚餘觸顧) = 壓鑰獵鹽願齋鏇觸鏇觸構齋窪憲選構願鏇網獵 (鹽膚遞鹹鹽憲觸獵鏇鑰, 5.9) 更多
ESC2024	N/A	-	-	Levosimendan infusion	衊衊蓋窪構鹽壓廠構餘(餘鹽衊鹹膚淵積餘蓋選) = 廠窪製鏇鹽廠積壓艱齋糧糧衊醖網齋顧鹽築顧 (壓願廠蓋積築蓋築積齋 ) 更多	-	2024-03-08
ESC2023	N/A	-	32	Intermittent levosimendan cycles	窪壓積夢餘繭壓鏇膚鹽(糧願積顧構壓鏇鏇壓醖) = 網衊鹽窪淵遞築觸觸積繭鏇積蓋襯鬱顧憲餘鹽 (膚衊獵獵艱選網網鏇願, 19 ~ 25)	-	2023-05-22