WILMINGTON, Del.--(BUSINESS WIRE)--AstraZeneca today announced the initiation of a Phase III trial to investigate the potential effect of triple-combination inhaled therapy BREZTRI AEROSPHERE® (budesonide/glycopyrronium/formoterol fumarate, or BGF) on severe cardiopulmonary outcomes, including death*, in people with chronic obstructive pulmonary disease (COPD) who also have elevated cardiopulmonary risk, irrespective of their exacerbation history.1.

特拉华州威尔明顿（商业新闻短讯）--阿斯利康今天宣布启动一项III期临床试验，以研究三联吸入疗法BREZTRI AEROSPHERE®（布地奈德/格隆溴铵/富马酸福莫特罗，或BGF）对慢性阻塞性肺疾病（COPD）患者严重心肺功能结局的潜在影响，包括死亡*无论他们的恶化史如何，他们的心肺风险也升高。

Also, the first participants have been dosed in ATHLOS, a Phase III trial investigating AstraZeneca’s triple therapy BGF vs. ICS/LABA budesonide/formoterol fumarate (BFF) or placebo on cardiopulmonary parameters including hyperinflation and exercise endurance time, which are associated with health status and survival.2.

此外，第一批参与者已经在ATHLOS中服用，这是一项III期试验，研究阿斯利康三联疗法BGF与ICS/LABA布地奈德/富马酸福莫特罗（BFF）或安慰剂对心肺参数的影响，包括过度充气和运动耐力时间，这与健康状况和生存率有关。

COPD impacts 391 million people globally.3 The disease’s mechanisms elevate the risk of both pulmonary and cardiac events, including severe or fatal COPD exacerbations and cardiac events, which is termed cardiopulmonary risk.4-8 This underlying risk is further increased after a COPD exacerbation and may remain elevated for up to a year following an exacerbation.9-11 Just one COPD exacerbation doubles the risk of a heart attack and increases risk of hospitalization and cardiopulmonary-related death.5,12-14 Cardiopulmonary causes are the most common reasons for death in patients with COPD.15,16.

COPD影响全球3.91亿人。3该疾病的机制增加了肺部和心脏事件的风险，包括严重或致命的COPD恶化和心脏事件，这被称为心肺风险。4-8这种潜在风险在COPD恶化后进一步增加，并且在恶化后可能会持续升高长达一年。9-11只有一次COPD恶化会使心脏病发作的风险增加一倍，并增加住院和心肺相关死亡的风险。5,12-14心肺原因是患者死亡的最常见原因患有COPD[15,16]。

Fernando Martinez, MD, MS, Chief of the Division of Pulmonary and Critical Care Medicine at Weill Cornell Medicine and New York-Presbyterian Hospital, and International Co-ordinating Investigator in the THARROS trial said, “The 2024 GOLD Report highlights the treatment effect of non-pharmacologic interventions and inhaled triple combination therapies on mortality.

Weill Cornell Medicine和纽约长老会医院肺部和重症监护医学科科长、医学博士Fernando Martinez女士以及THARROS试验的国际协调研究员表示：“2024年GOLD报告强调了非药物干预和吸入三联疗法对死亡率的治疗效果。

The Report calls for a more proactive therapeutic approach to improve outcomes in COPD. If positive, the THARROS trial will provide critical evidence about the potential of single inhaler, triple combination therapy to reduce severe cardiopulmonary events and further advance treatment goals in COPD, including for patients with no history of exacerbations, for whom no evidence currently exists.”

该报告呼吁采取更积极的治疗方法来改善COPD的预后。如果阳性，THARROS试验将提供关于单吸入器，三联疗法减少严重心肺事件和进一步推进COPD治疗目标的潜力的关键证据，包括目前没有证据的无恶化史患者。”

David Berg MD, MPH, Associate Physician in Cardiovascular and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, US added: “Large outcomes trials have transformed the management of cardiovascular diseases by enhancing our understanding of the potentially broad impact of therapies targeting those diseases.

美国哈佛医学院布莱根妇女医院心血管和重症监护医学副医师David Berg医学博士补充说：“大型结局试验通过增强我们对针对这些疾病的治疗的潜在广泛影响的理解，改变了心血管疾病的管理。

Current evidence already supports a proactive treatment approach in COPD. Now THARROS is seeking to provide first-of-its-kind evidence to support a strategy of comprehensive cardiopulmonary risk reduction with a triple therapy.”

目前的证据已经支持COPD的积极治疗方法。现在，THARROS正在寻求提供第一个此类证据，以支持通过三联疗法全面降低心肺风险的策略。”

Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “We have an important and urgent mission to eliminate COPD as a leading cause of death. Even moderate COPD exacerbations are associated with increased risks of further lung events, severe cardiovascular complications and have been shown to contribute to patients dying.

阿斯利康生物制药研发执行副总裁莎伦·巴尔（SharonBarr）表示：“我们有一项重要而紧迫的任务，即消除COPD作为主要死亡原因。即使是中度COPD恶化，也会增加进一步肺部事件的风险，严重的心血管并发症，并已被证明会导致患者死亡。

With the first-of-its-kind THARROS study, we aim to demonstrate the potential of triple therapy to address cardiopulmonary risk.”

通过首次THARROS研究，我们旨在证明三联疗法解决心肺风险的潜力。”

BGF is approved to treat COPD in 75 countries worldwide including the US, EU, China and Japan.

BGF被批准在全球75个国家（包括美国、欧盟、中国和日本）治疗COPD。

* The severe cardiopulmonary outcome measures investigated in THARROS include death from respiratory and cardiac causes.

*在THARROS调查的严重心肺结局指标包括呼吸和心脏原因导致的死亡。

BREZTRI AEROSPHERE® (budesonide/glycopyrronium/formoterol fumarate) Important Safety Information

BREZTRI AEROSPHERE®（布地奈德/格隆溴铵/富马酸福莫特罗）重要安全信息

BREZTRI is contraindicated in patients who have a hypersensitivity to budesonide, glycopyrrolate, formoterol fumarate, or product excipients

布地奈德、格隆溴铵、富马酸福莫特罗或产品赋形剂过敏的患者禁用BREZTRI

BREZTRI is not indicated for treatment of asthma. Long-acting beta2-adrenergic agonist (LABA) monotherapy for asthma is associated with an increased risk of asthma-related death. These findings are considered a class effect of LABA monotherapy. When a LABA is used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone.

BREZTRI不适用于治疗哮喘。长效β2肾上腺素能激动剂（LABA）单药治疗哮喘与哮喘相关死亡风险增加有关。这些发现被认为是LABA单一疗法的类别效应。当LABA与ICS固定剂量组合使用时，来自大型临床试验的数据显示，与单独使用ICS相比，严重哮喘相关事件（住院，插管，死亡）的风险没有显着增加。

Available data do not suggest an increased risk of death with use of LABA in patients with COPD.

现有数据并未表明COPD患者使用LABA会增加死亡风险。

BREZTRI should not be initiated in patients with acutely deteriorating COPD, which may be a life-threatening condition

急性恶化的COPD患者不应开始服用BREZTRI，这可能会危及生命

BREZTRI is NOT a rescue inhaler. Do NOT use to relieve acute symptoms; treat with an inhaled short-acting beta2-agonist

BREZTRI不是一种救援吸入器。不要用于缓解急性症状；吸入短效β2受体激动剂治疗

BREZTRI should not be used more often than recommended; at higher doses than recommended; or in combination with LABA-containing medicines, due to risk of overdose. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs.

BREZTRI的使用频率不应超过推荐的频率；剂量高于推荐剂量；或与含有LABA的药物联合使用，因为有过量服用的风险。据报道，过度使用吸入的拟交感神经药物会导致临床上显着的心血管效应和死亡。

Oropharyngeal candidiasis has occurred in patients treated with orally inhaled drug products containing budesonide. Advise patients to rinse their mouths with water without swallowing after inhalation

口服吸入含布地奈德的药物治疗的患者发生口咽念珠菌病。建议患者在吸入后用水漱口，不要吞咽

Lower respiratory tract infections, including pneumonia, have been reported following ICS. Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of pneumonia and exacerbations frequently overlap

ICS后已报告下呼吸道感染，包括肺炎。由于肺炎和恶化的临床特征经常重叠，医生应警惕COPD患者肺炎的可能发展

Due to possible immunosuppression, potential worsening of infections could occur. Use with caution. A more serious or fatal course of chickenpox or measles can occur in susceptible patients

由于可能的免疫抑制，感染可能会恶化。请谨慎使用。易感患者可能会出现更严重或致命的水痘或麻疹病程

Particular care is needed for patients transferred from systemic corticosteroids to ICS because deaths due to adrenal insufficiency have occurred in patients during and after transfer. Taper patients slowly from systemic corticosteroids if transferring to BREZTRI

从全身皮质类固醇转移到ICS的患者需要特别注意，因为在转移期间和之后，患者因肾上腺功能不全而死亡。如果转移到BREZTRI，慢慢减少患者全身皮质类固醇的使用

Hypercorticism and adrenal suppression may occur with regular or very high dosage in susceptible individuals. If such changes occur, consider appropriate therapy

在易感个体中，经常或非常高的剂量可能会发生皮质醇增多症和肾上腺抑制。如果发生这种变化，请考虑适当的治疗

Caution should be exercised when considering the coadministration of BREZTRI with long-term ketoconazole and other known strong CYP3A4 Inhibitors. Adverse effects related to increased systemic exposure to budesonide may occur

当考虑将BREZTRI与长期酮康唑和其他已知的强CYP3A4抑制剂合用时，应谨慎行事。可能会发生与布地奈德全身暴露增加有关的不良反应

If paradoxical bronchospasm occurs, discontinue BREZTRI immediately and institute alternative therapy

如果发生反常的支气管痉挛，立即停止布雷兹特里并进行替代治疗

Anaphylaxis and other hypersensitivity reactions (eg, angioedema, urticaria or rash) have been reported. Discontinue and consider alternative therapy

已经报道了过敏反应和其他超敏反应（例如血管性水肿，荨麻疹或皮疹）。停止并考虑替代疗法

Use caution in patients with cardiovascular disorders, especially coronary insufficiency, as formoterol fumarate can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, and also cardiac arrhythmias, such as supraventricular tachycardia and extrasystoles.

对于心血管疾病患者，尤其是冠状动脉功能不全患者，请谨慎使用，因为富马酸福莫特罗可以在某些患者中产生临床上显着的心血管作用，这可以通过脉搏率，收缩压或舒张压的增加以及心律失常（如室上性心动过速和收缩期前）来衡量。

Decreases in bone mineral density have been observed with long-term administration of ICS. Assess initially and periodically thereafter in patients at high risk for decreased bone mineral content

长期服用ICS可观察到骨矿物质密度降低。对骨矿物质含量降低的高危患者进行初步和定期评估

Glaucoma and cataracts may occur with long-term use of ICS. Worsening of narrow-angle glaucoma may occur, so use with caution. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use BREZTRI long term. Instruct patients to contact a healthcare provider immediately if symptoms occur.

长期使用ICS可能会发生青光眼和白内障。窄角型青光眼可能会恶化，因此请谨慎使用。对于出现眼部症状或长期使用BREZTRI的患者，请考虑转诊给眼科医生。指示患者在出现症状时立即联系医疗保健提供者。

Worsening of urinary retention may occur. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to contact a healthcare provider immediately if symptoms occur

尿潴留可能会恶化。前列腺增生或膀胱颈梗阻患者应谨慎使用。指示患者在出现症状时立即联系医疗保健提供者

Use caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis or unusually responsive to sympathomimetic amines

惊厥性疾病、甲状腺毒症、糖尿病和酮症酸中毒或对拟交感神经胺反应异常的患者要谨慎

Be alert to hypokalemia or hyperglycemia

警惕低钾血症或高血糖

Most common adverse reactions in a 52-week trial (incidence ≥ 2%) were upper respiratory tract infection (5.7%), pneumonia (4.6%), back pain (3.1%), oral candidiasis (3.0%), influenza (2.9%), muscle spasms (2.8%), urinary tract infection (2.7%), cough (2.7%), sinusitis (2.6%), and diarrhea (2.1%). In a 24-week trial, adverse reactions (incidence ≥ 2%) were dysphonia (3.3%) and muscle spasms (3.3%).

52周试验中最常见的不良反应（发生率≥2%）为上呼吸道感染（5.7%），肺炎（4.6%），背痛（3.1%），口腔念珠菌病（3.0%），流感（2.9%），肌肉痉挛（2.8%），尿路感染（2.7%），咳嗽（2.7%），鼻窦炎（2.6%）和腹泻（2.1%）。在为期24周的试验中，不良反应（发生率≥2%）为发音困难（3.3%）和肌肉痉挛（3.3%）。

BREZTRI should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors and tricyclic antidepressants, as these may potentiate the effect of formoterol fumarate on the cardiovascular system

对于接受单胺氧化酶抑制剂和三环类抗抑郁药治疗的患者，应极其谨慎地服用BREZTRI，因为这些药物可能会增强富马酸福莫特罗对心血管系统的影响

BREZTRI should be administered with caution to patients being treated with:

对于接受以下治疗的患者，应谨慎使用BREZTRI：

Strong cytochrome P450 3A4 inhibitors (may cause systemic corticosteroid effects)

强细胞色素P450 3A4抑制剂（可能引起全身皮质类固醇作用）

Adrenergic drugs (may potentiate effects of formoterol fumarate)

肾上腺素能药物（可能增强富马酸福莫特罗的作用）

Xanthine derivatives, steroids, or non-potassium sparing diuretics (may potentiate hypokalemia and/or ECG changes)

黄嘌呤衍生物、类固醇或非保钾利尿剂（可能增强低钾血症和/或心电图改变）

Beta-blockers (may block bronchodilatory effects of beta-agonists and produce severe bronchospasm)

β受体阻滞剂（可能阻断β受体激动剂的支气管扩张作用并产生严重的支气管痉挛）

Anticholinergic-containing drugs (may interact additively). Avoid use with BREZTRI

含抗胆碱能药物（可能相互作用）。避免与BREZTRI一起使用

Use BREZTRI with caution in patients with hepatic impairment, as budesonide and formoterol fumarate systemic exposure may increase. Patients with severe hepatic disease should be closely monitored

布地奈德和富马酸福莫特罗全身暴露可能会增加，因此在肝功能损害患者中应谨慎使用BREZTRI。应密切监测重症肝病患者

INDICATION

指示

BREZTRI AEROSPHERE is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).

BREZTRI大气层适用于慢性阻塞性肺疾病（COPD）患者的维持治疗。

LIMITATIONS OF USE

使用限制

Not indicated for the relief of acute bronchospasm or for the treatment of asthma.

不适用于缓解急性支气管痉挛或治疗哮喘。

Please see full BREZTRI Prescribing Information, including Patient Information.

请参阅完整的BREZTRI处方信息，包括患者信息。

You may report side effects related to AstraZeneca products.

您可能会报告与阿斯利康产品有关的副作用。

Notes

注意事项

COPD

慢性阻塞性肺疾病

COPD refers to a group of lung diseases, including chronic bronchitis and emphysema, that cause airflow blockage and breathing-related problems.17 Affecting an estimated 16 million Americans, COPD is the third leading cause of death due to chronic disease and the sixth overall leading cause of death in the US.18,19.

COPD是指一组肺部疾病，包括慢性支气管炎和肺气肿，会导致气流阻塞和呼吸相关问题[17]。估计有1600万美国人患有COPD，COPD是慢性病死亡的第三大原因，也是美国第六大主要死亡原因[18,19]。

BREZTRI AEROSPHERE®

布雷兹特里大气层®

BREZTRI AEROSPHERE (budesonide/glycopyrronium/formoterol fumarate) is a single-inhaler, fixed-dose triple-combination of formoterol fumarate, a LABA, glycopyrronium bromide, a LAMA, with budesonide, an ICS, and delivered in a pressurized metered-dose inhaler. BREZTRI AEROSPHERE is approved to treat COPD in more than 50 countries worldwide including the US, EU, China and Japan, and is currently being studied in Phase III trials for asthma..

BREZTRI气层（布地奈德/格隆溴铵/富马酸福莫特罗）是一种单吸入器，固定剂量的富马酸福莫特罗，LABA，格隆溴铵，LAMA与布地奈德（ICS）的三重组合，并以加压计量吸入器输送。BREZTRI AEROSPHERE已被批准在包括美国、欧盟、中国和日本在内的全球50多个国家治疗COPD，目前正在进行哮喘的III期临床试验。。

THARROS

错误

THARROS is a randomized, multi-center, double-blind, parallel-group trial to investigate the effect of budesonide/glycopyrronium/formoterol fumarate (BGF) on cardiopulmonary outcomes in COPD patients. Approximately 5,000 COPD patients with cardiopulmonary risk, aged 40-80 years old, will be randomized to receive either fixed-dose triple combination therapy, BGF, or a dual bronchodilator therapy glycopyrronium/formoterol fumarate.

THARROS是一项随机，多中心，双盲，平行组试验，旨在研究布地奈德/格隆溴铵/富马酸福莫特罗（BGF）对COPD患者心肺结局的影响。大约5000名40-80岁有心肺风险的COPD患者将随机接受固定剂量三联疗法，BGF或双支气管扩张剂治疗格隆溴铵/富马酸福莫特罗。

The trial uses a novel composite endpoint combining respiratory and cardiac outcomes: the primary endpoint in the THARROS trial is time to first severe cardiac event, severe COPD exacerbation, or cardiopulmonary death.1.

该试验使用了一种结合呼吸和心脏结局的新型复合终点：THARROS试验的主要终点是首次发生严重心脏事件，严重COPD恶化或心肺死亡的时间。

ATHLOS

ATHLOS

ATHLOS is a randomized, multi-center, double-blind, three-treatment, three-period, cross-over study to investigate the effect of budesonide/glycopyrronium/formoterol fumarate vs budesonide/formoterol fumarate (an ICS/LABA) or placebo on isotime inspiratory capacity (IC) and exercise endurance time in participants with COPD who have exertional breathlessness despite treatment with monotherapy or dual COPD maintenance therapy.

ATHLOS是一项随机，多中心，双盲，三治疗，三期，交叉研究，旨在研究布地奈德/格隆溴铵/富马酸福莫特罗与布地奈德/富马酸福莫特罗（ICS/LABA）或安慰剂对等时吸气能力（IC）的影响和COPD患者的运动耐力时间，尽管使用单一疗法或双重COPD维持疗法治疗，但仍有劳力性呼吸困难。

This study will include 180 patients aged 40-80 years.2.

本研究将包括180名40-80岁的患者。

AstraZeneca in Respiratory & Immunology

阿斯利康呼吸与免疫学

Respiratory & Immunology, part of AstraZeneca BioPharmaceuticals is a key disease area and growth driver to the Company.

呼吸与免疫学是阿斯利康生物制药的一部分，是该公司的关键疾病领域和增长驱动力。

AstraZeneca is an established leader in respiratory care with a 50-year heritage and a growing portfolio of medicines in immune-mediated diseases. The Company is committed to addressing the vast unmet needs of these chronic, often debilitating, diseases with a pipeline and portfolio of inhaled medicines, biologics and new modalities aimed at previously unreachable biologic targets.

阿斯利康是呼吸系统护理领域的公认领导者，拥有50年的历史，并且在免疫介导疾病方面的药物组合不断增加。该公司致力于通过吸入药物、生物制剂和针对以前无法达到的生物目标的新模式的管道和组合，解决这些慢性病（通常使人衰弱）的巨大未满足需求。

Our ambition is to deliver life-changing medicines that help eliminate COPD as a leading cause of death, eliminate asthma attacks and achieve clinical remission in immune-mediated diseases..

我们的目标是提供改变生命的药物，帮助消除COPD作为主要死亡原因，消除哮喘发作，并实现免疫介导疾病的临床缓解。。

About AstraZeneca

关于阿斯利康

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries, and its innovative medicines are used by millions of patients worldwide.

阿斯利康是一家以科学为主导的全球生物制药公司，专注于肿瘤学、罕见病和生物制药（包括心血管、肾脏和代谢以及呼吸和免疫学）处方药的发现、开发和商业化。阿斯利康总部位于英国剑桥，在100多个国家开展业务，其创新药物被全球数百万患者使用。