Multicenter clinical trial of hANP therapy on outpatient for heart failure. - Multicenter clinical trial of hANP therapy on outpatient for heart failure.

开始日期2019-04-06

申办/合作机构-

JPRN-JMA-IIA00379 / Recruiting临床2期IIT

SUN4936c clinical trial phase 2An exploratory clinical trial of safety and efficacy of SUN4936c for preventing contrast-induced nephropathy in patients with renal dysfunction who are planned to receive iodine contrast

开始日期2018-09-04

申办/合作机构-

100 项与卡培立肽相关的临床结果

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100 项与卡培立肽相关的转化医学

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100 项与卡培立肽相关的专利（医药）

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492

项与卡培立肽相关的文献（医药）

2024-09-16·Journal of Pharmaceutical Health Care and Sciences

Changes in urinary output due to concomitant administration of sacubitril/valsartan and atrial natriuretic peptide in patients with heart failure: a multicenter retrospective cohort study.

Article

作者: Yamamoto, Yoshiaki ; Yanagawa, Tatsuki ; Kondo, Yoshihiro ; Kato, Hidekazu ; Aoki, Maria ; Yamamoto, Takanori ; Asai, Yuki ; Zakoji, Nobuyuki ; Ootsuki, Shinnosuke ; Hosoe, Shingo ; Takahashi, Masaaki

BACKGROUND:

Sacubitril/valsartan is an angiotensin receptor neprilysin inhibitor (ARNI) that inhibits the degradation of endogenous natriuretic peptides. Therefore, ARNIs may increase the efficacy of human atrial natriuretic peptide (hANP), a drug for acute heart failure, by mediating its pharmacological mechanism. This study was aimed at evaluating the effects of ARNIs on the pharmacological effects of hANP by using surrogate marker, such as urinary output, in patients with heart failure.

METHODS:

In this multicenter retrospective cohort study, adult patients with heart failure who were taking angiotensin II receptor blockers (ARB) or ARNIs combined with hANP were enrolled. Information on basic characteristics, clinical laboratory data, medical history, and severity of cardiac insufficiency were collected from electronic medical records. The primary outcome was the change in adjusted fluid balance, calculated by IN-volume (mL/day) - OUT-volume (mL/day) / daily hANP dosage (μg).

RESULTS:

Ninety-two and 62 patients in the ARB + hANP and ARNI + hANP groups, respectively, were eligible for analysis. The adjusted fluid balance in the ARNI + hANP group was significantly lower than that in the ARB + hANP group (p = 0.001). After propensity score matching, 27 patients from each group were included. Similarly, there was a significant reduction in adjusted fluid balance in the ARNI + hANP group after propensity score matching (p = 0.026).

CONCLUSIONS:

These findings suggest that ARNIs may enhance the efficacy of hANP and the combination of the two may be effective in the treatment of heart failure.

2024-07-01·Naunyn-Schmiedeberg's archives of pharmacology

MitoQ and its hyaluronic acid–based nanopreparation mitigating gamma radiation–induced intestinal injury in mice: alleviation of oxidative stress and apoptosis

Article

作者: Karam, Heba M ; Dawoud, Mohamed ; Ibrahim, Ismail T ; Ibrahim, Ayman A ; Attallah, Khalid M

Perturbations produced by ionizing radiation on intestinal tissue are considered one of highly drastic challenges in radiotherapy. Animals were randomized into five groups. The first group was allocated as control, and the second was subjected to whole body γ-irradiation (10 Gy). The third was administered HA NP (17.6 mg/kg/day; i.p.) and then irradiated. The fourth one received MitoQ (2 mg/kg/day; i.p.) and then irradiated. The last group received MitoQ/HA NP (2 mg/kg/day; i.p.) for 5 days prior to irradiation. Mice were sacrificed a week post-γ-irradiation for evaluation. MitoQ/HA NP ameliorated mitochondrial oxidative stress as indicated by rising (TAC) and glutathione peroxidase and decreasing malondialdehyde, showing its distinguished antioxidant yield. That impacted the attenuation of apoptosis, which was revealed by the restoration of the anti-apoptotic marker and lessening proapoptotic caspase-3. Inflammatory parameters dwindled via treatment with MitoQ/HA NP. Moreover, this new NP exerts its therapeutic action through a distinguished radioprotective pathway (Hmgb1/TLR-4.) Subsequently, these antioxidants and their nanoparticles conferred protection to intestinal tissue as manifested by histopathological examination. These findings would be associated with its eminent antioxidant potential through high mitochondria targeting, enhanced cellular uptake, and ROS scavenging. This research underlines MitoQ/HA NP as a new treatment for the modulation of intestinal damage caused by radiotherapy modalities.

2024-07-01·EBioMedicine

Advancing drug development for atrial fibrillation by prioritising findings from human genetic association studies

Article

作者: Providencia, Rui ; Lambiase, Pier D ; Finan, Chris ; Schilling, Richard ; Floriaan Schmidt, Amand ; Kukendrarajah, Kishore ; Farmaki, Aliki-Eleni

BACKGROUND:

Drug development for atrial fibrillation (AF) has failed to yield new approved compounds. We sought to identify and prioritise potential druggable targets with support from human genetics, by integrating the available evidence with bioinformatics sources relevant for AF drug development.

METHODS:

Genetic hits for AF and related traits were identified through structured search of MEDLINE. Genes derived from each paper were cross-referenced with the OpenTargets platform for drug interactions. Confirmation/validation was demonstrated through structured searches and review of evidence on MEDLINE and ClinialTrials.gov for each drug and its association with AF.

FINDINGS:

613 unique drugs were identified, with 21 already included in AF Guidelines. Cardiovascular drugs from classes not currently used for AF (e.g. ranolazine and carperitide) and anti-inflammatory drugs (e.g. dexamethasone and mehylprednisolone) had evidence of potential benefit. Further targets were considered druggable but remain open for drug development.

INTERPRETATION:

Our systematic approach, combining evidence from different bioinformatics platforms, identified drug repurposing opportunities and druggable targets for AF.

FUNDING:

KK is supported by Barts Charity grant G-002089 and is mentored on the AFGen 2023-24 Fellowship funded by the AFGen NIH/NHLBI grant R01HL092577. RP is supported by the UCL BHF Research Accelerator AA/18/6/34223 and NIHR grant NIHR129463. AFS is supported by the BHF grants PG/18/5033837, PG/22/10989 and UCL BHF Accelerator AA/18/6/34223 as well as the UK Research and Innovation (UKRI) under the UK government's Horizon Europe funding guarantee EP/Z000211/1 and by the UKRI-NIHR grant MR/V033867/1 for the Multimorbidity Mechanism and Therapeutics Research Collaboration. AF is supported by UCL BHF Accelerator AA/18/6/34223. CF is supported by UCL BHF Accelerator AA/18/6/34223.

项与卡培立肽相关的新闻（医药）

2024-09-14

·奇点网

《自然》：心衰治疗变革在即！科学家开发全新利钠肽受体激动剂类药物，受限少、半衰期长丨临床大发现

*仅供医学专业人士阅读参考新药来了！心力衰竭的治疗方式变革在即。美国学者Michael E. Dunn等人[1]开发出一种靶向利钠肽受体（NPR1）的新型激动剂单克隆抗体REGN5381，能够有效降低静脉压力，并持久改善心力衰竭患者和动物模型的血液动力学状态。首次临床试验显示，单次注射100mg剂量的REGN5381可使健康成年人的收缩压降低6-9 mmHg，效果持续3天，耐受性良好。 REGN5381能够避免现有的利钠肽类药物频繁输注的限制，并且未引发显著的利尿等副作用，或将成为心力衰竭长期管理的有效解决方案。不只是心力衰竭。妙佑医疗国际的John C. Burnett Jr研究员点评道[2]，虽然该研究的主要临床目标是心力衰竭，但由于NPR1信号通路具有广泛的生理效应，因此这种能够在NPR1上产生持续效应的抗体，未来还可能拓展用于治疗其他疾病，如高血压、肥胖症。论文于近日发表在《自然》上。论文首页截图心力衰竭是一种全球范围内严重的健康问题，主要表现为心脏无法有效泵血导致静脉充血，出现肺水肿、胸腔积液、腹水等症状。在心力衰竭的情况下，人体的心肌细胞受到牵拉，会释放心房利钠肽 (ANP)、脑利钠肽 (BNP) ，作用于利钠肽受体（NPR1）后触发血管舒张来进行自我保护。增强ANP和BNP介导的信号通路已成为治疗心力衰竭的潜在有效方法。目前主要有两种药物策略：一种是静脉输注给药人重组利钠肽，比如人重组ANP药物卡培立肽，能够短暂缓解静脉压力，但因ANP和BNP的半衰期较短，患者必须住院完成持续输注治疗；另一种方法是想方设法减少内源性ANP和BNP在体内的降解，抑制相应降解酶的活性，再与阻断血管收缩的药物联合使用，比如沙库巴曲缬沙坦钠，可以通过口服给药方式治疗慢性心力衰竭，但这种疗法可能受限于患者自身的ANP、BNP表达情况。此次，围绕ANP和BNP，研究者们为心力衰竭的长效药物治疗给出了新的解法。尽管通过抗体激活受体的疗法在癌症等疾病的治疗中已被广泛应用，但这类药物在心血管疾病中的使用仍处于早期阶段。在这项研究中，为确认NPR1作为心力衰竭治疗靶点的合理性，研究者们对6个队列和5个不同种族群体的718386人进行了遗传学分析。结果显示，NPR1功能丧失变异（LOF）与血压升高、心力衰竭生物标志物（NT-proBNP）水平增加和心力衰竭风险增高，而功能增强变异（GOF）反之。 NPR1基因变异与血压、心力衰竭的关联这些结果确立了NPR1作为治疗靶点的可行性，说明长期激活NPR1对心力衰竭患者有益。接下来，研究者们使用高通量筛选技术，找到了能够有效激活NPR1的最佳单克隆抗体——REGN5381。与刚才提到的两种治疗策略相比，REGN5381的独特之处在于，它能够在没有ANP或BNP这些天然配体的情况下，自身直接结合并激活NPR1，使NPR1处于类活性状态，进而激活下游的鸟苷酸环化酶（cGMP）信号通路，经过级联反应诱导血管舒张等缓解心力衰竭；当有ANP或BNP存在时，效果增强。 REGN5381在ANP存在下增强NPR1二聚体的激活；即使没有ANP，REGN5381也能诱导NPR1二聚体构象改变[2] 体外实验和小鼠、比格犬、食蟹猴实验结果显示，皮下注射REGN5381能够对血管产生扩张作用，且这种作用在静脉中比在动脉中更为显著。REGN5381治疗显著增加了cGMP的产生，并且在最高剂量下对小鼠的降压效果可持续28天。当REGN5381与血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂联合使用时，显示出协同作用。虽然ANP和BNP的典型作用包括利尿和排纳，但动物实验结果指出，REGN5381不会有利尿这种副作用。于是，研究者们展开了REGN5381的首次临床试验。他们招募了48名健康成年人，随机分为不同剂量组，接受单次静脉注射REGN5381或安慰剂。在最高剂量（100mg）下，REGN5381治疗组的收缩压下降了6-9mmHg，且这一效果持续72小时。此外，试验结果还表明，REGN5381与心率适度增加、脉压缩小和每搏输出量减少相关，同时伴有尿液中cGMP水平的升高，但不会增加参与者的排尿量。试验中未发现严重的不良反应，REGN5381总体耐受性良好，常见的不良反应为体位性眩晕、直立性低血压等，但这些反应与剂量无关。 REGN5381可降低健康成年人的收缩压和每搏输出量，并增加脉搏频率 REGN5381作为一种长效NPR1激动剂，在动物和首次临床试验中均展示了其强大的治疗潜力。REGN5381能够持久降低静脉压力，可以避免频繁输注的困扰，并且不产生显著的副作用。对此，John C. Burnett Jr提出[2]，未来的关键研究方向应该是评估REGN5381在不同ANP和BNP水平的心力衰竭患者中的疗效，从而确定最适合该疗法的患者群体。此外，REGN5381对动脉、静脉的扩张效果还需要在人类临床试验中更多验证。让我们拭目以待，REGN5381在心力衰竭临床试验中的进一步成果。奇点糕近期推出了《2024ASCO年会深度盘点》课程，为大家系统盘点了2024ASCO年会上实体瘤领域的重磅进展，让您在100分钟内迅速深入把握前沿。长按识别下图中的二维码即可购买，购买后您可以在「奇点网小程序」收听，或下载奇点网「医学奇点」苹果客户端收听。如果遇到任何技术问题大家可以戳我们下图中的客服小伙伴来解决~~ 参考文献： [1]https://www.nature.com/articles/s41586-024-07903-1 [2]https://www.nature.com/articles/d41586-024-02660-7 本文作者丨张艾迪

临床结果

2023-04-26

·PRNewswire

The Role of Natriuretic Peptides in the Diagnosis and Management of Heart Failure Discussed in New Joint Scientific Statement by the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, and Japanese Heart Failure Society

ROCKVILLE, Md., April 26, 2023 /PRNewswire/ -- The Heart Failure Society of America (HFSA), the Heart Failure Association of the European Society of Cardiology (HFA-ESC) and the Japanese Heart Failure Society (JHFS) announced today a joint scientific statement on Natriuretic Peptides: Role in the Diagnosis and Management of Heart Failure. Natriuretic peptides, brain (B-type) natriuretic peptide (BNP) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP), are internationally used as a biomarker for diagnosis and management in adults with heart failure (HF). In addition, natriuretic peptide biomarker data can be important in risk stratification of heart failure prognosis. In addition to biomarker data, implementation of an oral angiotensin receptor neprilysin inhibitor (ARNI) has increased healthcare professionals' awareness of natriuretic peptides as an important therapeutic agent. Natriuretic Peptides: Role in the Diagnosis and Management of Heart Failure scientific statement aims to provide a framework and expert recommendations to healthcare professionals on the diagnosis and management of HF and focuses on the following areas: History and basic research: discovery, production, and cardiovascular protection Diagnostic and prognostic biomarkers: acute HF, chronic HF, inclusion/endpoint in clinical trials, and natriuretic peptides-guided therapy Therapeutic use: nesiritide (BNP), carperitide (ANP), and sacubitril (neprilysin inhibitor [combined with an angiotensin receptor blocker]), and Gaps in knowledge and future directions Standardized screening for HF remains challenging because of the heterogeneity of risk factors across different patient populations. Natriuretic peptides are recommended for initial diagnosis of HF as noted in the 2022 ACC/AHA/HFSA Guideline for the Management of HF, 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic HF, and JCS2017/JHF2017 Guideline on diagnosis and treatment of acute and chronic HF. "There are several differences in the statements among HF Societies regarding the use of natriuretic peptides as biomarkers for risk stratification and prevention. The scientific statement provides up-to-date perspectives and guidance that healthcare professionals can use to navigate and provide the best care for their patients with HF," Nancy Albert, PhD, CCNS, CHFN; co-chair and co-author representing HFSA in the Trilateral International Consensus Conference (TICC) said. The joint scientific statement on natriuretic peptides was developed by the TICC, a collaboration of HFSA, JHFS and HFSA-ESC. The TICC 2021 was hosted by the JHFS and was chaired by Hiroyuki Tsutsui, President of the JHFS, with Nancy M. Albert (HFSA) and Andrew Coats (HFA-ESC) serving as co-chairs. The Natriuretic Peptides: Role in the Diagnosis and Management of Heart Failure scientific statement will jointly publish on Monday 17 April at 9:00 AM EDT in the Journal of Cardiac Failure, the official journal of the HFSA and the JHFS, and the European Journal of Heart Failure, the official journal of the HFA-ESC. DOI: 10.1016/j.cardfail.2023.02.009 To receive a copy of the manuscript in advance of the embargo, contact [email protected]. About the Heart Failure Society of America The Heart Failure Society of America, Inc. (HFSA) represents the first organized effort by heart failure experts from the Americas to provide a forum for all those interested in heart function, heart failure, and congestive heart failure (CHF) research and patient care. The mission of HFSA is to provide a platform to improve and expand heart failure care through collaboration, education, innovation, research, and advocacy. HFSA members include physicians, scientists, nurses, nurse practitioners, pharmacists, trainees, other healthcare workers and patients. For more information, visit hfsa.org. About the Heart Failure Association of the European Society of Cardiology As the world's largest heart failure association, the Heart Failure Association of the ESC prioritizes patient management and awareness of heart failure as a global health problem. HFA-ESC's mission is to improve quality of life and longevity through better prevention, diagnosis and treatment of heart failure, including the establishment of networks for its management, education and research. Learn more online. About the Japanese Heart Failure Society In response to the increased interest in heart failure, based on the basic studies on its mechanisms and clinical trials, the Japanese Heart Failure Society (JHFS) was established in 1996. The first General and Scientific Meeting of the JHFS was held in October 1997 at the Kyoto International Conference Center. The number of members increased from 900 to approximately 4000 in 2020. The vision of JHFS is to enrich the happy life of the patients and their families through investigating the basic pathophysiology of heart failure, and developing the effective and efficient diagnosis, prevention and treatment strategies. About the Journal of Cardiac Failure The Journal of Cardiac Failure (JCF) publishes the highest quality science in the field of heart failure with a focus on diversity, equity, and inclusion, mentorship, multidisciplinary partnerships, and patient-centeredness. Published papers span original investigator-initiated work to state-of-the-art reviews, guidelines and scientific statements, expert perspectives, early career and trainee spotlight pieces, patient and patient-partner narratives. JCF also emphasizes the power of language and prioritizes innovative approaches to dissemination of published work to reach and impact the broader heart failure community. For more information, visit onlinejcf.com. About the European Journal of Heart Failure The European Journal of Heart Failure (EJHF) is dedicated to the advancement of knowledge in the field of heart failure management. The journal publishes reviews and editorials to improve the understanding, prevention, investigation and treatment of heart failure. Molecular and cellular biology, pathology, physiology, electrophysiology, pharmacology, as well as clinical, social and population sciences all form part of the discipline. Visit EJHF online. Media Contact: Laura Poko: Director of Marketing and Communications, Heart Failure Society of America, 301-798-4493, ext. 226 [email protected] Olivia Seward: Associate Director Communication, European Society of Cardiology, +33 (0)4 89 87 20 10, [email protected] SOURCE Heart Failure Society of America

100 项与卡培立肽相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D03328	卡培立肽	C01DX	-

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	日本	Daiichi Sankyo Co., Ltd.	1995-01-20

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
心肌梗塞	临床3期	日本	Asubio Pharma Co. Ltd.	-
慢性肾病	临床2期	日本	Gunma University	2015-05-21
心肌疾病	临床2期	美国	Daiichi Sankyo, Inc.	2004-01-01
心肌疾病	临床2期	加拿大	Daiichi Sankyo, Inc.	2004-01-01
左心室功能不全	临床2期	美国	Daiichi Sankyo, Inc.	2004-01-01
左心室功能不全	临床2期	加拿大	Daiichi Sankyo, Inc.	2004-01-01
成人呼吸窘迫综合征	临床2期	-	Suntory Pharmaceutical Research Laboratories LLC	1999-12-01