CTRI/2024/12/078263尚未招募3 期
A Randomized, Double-blind, Parallel Group, Multi-center, Phase III Study to Assess the Efficacy of Budesonide, Glycopyrronium, and Formoterol Fumarate Metered Dose Inhaler Relative to Glycopyrronium and Formoterol Fumarate MDI on Cardiopulmonary Outcomes in Chronic Obstructive Pulmonary Disease (THARROS)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 5,000
- 试验地点
- 17
- 主要终点
- Evaluate the effect of BGF MDI 320/14.4/9.6μg compared with GFF MDI 14.4/9.6μg On cardiopulmonary outcomes
研究概览
简要总结
This study seeks to confirm previous findings and aims to demonstrate that triple ICS/LAMA/LABA therapy with BGF MDI 320/14.4/9.6 µg (Breztri/Trixeo) will improve cardiopulmonary outcomes relative to LAMA/LABA therapy with GFF MDI 14.4/9.6 µg (Bevespi) in a population with COPD and high cardiopulmonary risk. The study’s primary composite endpoint is time to first severe cardiac or COPD event. The composite primary endpoint comprises time to the first HF acute healthcare visit/hospitalization, MI hospitalization, severe COPD exacerbation, or cardiopulmonary death.
Evaluating a combined cardiopulmonary outcome assessing key clinical deteriorations that captures mortality and hospitalization (ie, cardiac/COPD hospitalization and cardiopulmonary death) is important in patients with COPD and elevated cardiac risk given cardiopulmonary outcomes are fundamental features of the disease. AstraZeneca considers this of key importance to prescribers treating both pulmonary and cardiac diseases. The data from the clinical question at hand, whether BGF MDI reduces severe cardiopulmonary outcomes in a population not on ICS therapy, will be novel with the potential to change clinical practice
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 40.00 Year(s) 至 80.00 Year(s)（—）
- 性别
- Male
入选标准
- •1.Male or female participants must be 40 to 80 years of age inclusive, at the time of signing the ICF. Type of Participant and Disease Characteristics 2.Demonstrate acceptable MDI administration technique at Visit 1 and Visit 2 (randomization). NOTE:Historical use of a spacer device within the 8 weeks prior to and/or during the Screening and Randomized Treatment Periods is not permitted 3.A diagnosis of COPD confirmed by a post-bronchodilator FEV1/FVC ratio less than 70% at Visit
- •4.Current or former smokers with a history of at least 10 pack-years of cigarette smoking; defined as (number of cigarettes per day/20) x number of years smoked. Previous smokers are defined as those who have stopped smoking for at least 6 months prior to Visit
- •NOTE: Pipe, cigar, and/or electronic cigarette use cannot be used to calculate pack-year history. 5.A baseline peripheral blood eosinophil count of greater than or equal 100 cells/mm3 assessed at Visit 1 by the central laboratory 6.A CAT score of greater than or equal to 10 at V
- •Each of the phlegm (sputum) and cough item sub-scores must be greater than or equal
- •7.Participant must fulfill at least 1 of the 4 CV disease/risk factor criteria below [(a), (b), (c), or (d)]. A minimum of 50% of participants must meet criterion (a): (a)Established CV disease defined as documented evidence of any of the following: -angina pectoris with objective evidence of myocardial ischemia -myocardial infarction -percutaneous coronary intervention -coronary artery bypass grafting -objective findings of coronary stenosis (greater than or equal 50%) in at least 2 coronary artery territories (ie, left anterior descending, ramus intermedius, left circumflex, right coronary artery) involving the main vessel, a major branch, or a bypass graft -chronic heart failure with NYHA Class II-III functional limitation at V
- •NOTE:No more than 10% of participants should enter through only the heart failure criterion. -NYHA Class II is defined as patients comfortable at rest; ordinary physical activity results in fatigue, palpitations, breathlessness, or angina pectoris -NYHA Class III is defined as patients comfortable at rest, but with less than ordinary physical activity causing fatigue, dyspnea, palpitations, or angina NOTE:NYHA Class IV is not inclusionary and is defined as patients experiencing symptoms even while at rest. -peripheral arterial disease (any of the following): -peripheral arterial intervention, stenting surgical revascularization -lower extremity amputation as a result of peripheral arterial obstructive disease -current symptoms of intermittent claudication AND ankle/brachial index less than 90 documented within the last 12 months -angiographic evidence of peripheral artery disease (b)Combination of any 3 of the following 5 CV risk factors: -Hypertension (at least one of the following):.
- •A documented history (in the previous 6 months) of BP greater than 140/90 mm/Hg confirmed at Visit 1 with both an elevated systolic BP (greater than 140 mmHg) and an elevated diastolic BP (greater than 90 mmHg) on the last 2 of 3 measurements -Receiving at least one anti-hypertensive therapy prescribed by a physician for BP lowering. -Documented history of diabetes mellitus -Documented history of chronic kidney disease, with eGFR greater than or equal 20 mL/min/1.73 m2 and less than 60 mL/min/1.73 m2 measured at Visit
- •Documented history of dyslipidemia in previous 12 months defined as at least one of the following: -An LDL-C greater than 130 mg/dL (3.36 mmol/L) measured at Visit
- •An HDL-C less than 40 mg/dL (1.03 mmol/L) for men or less than 50 mg/dL (1.29 mmol/L) for women measured at V
- •On lipid lowering therapy prescribed by a physician for hypercholesterolemia (LDL-C greater than 130 mg/dL [3.36 mmol/L]) for greater than 12 months. This should be verified by documentation of a laboratory value LDL-C of greater than 130 mg/dL (3.36 mmol/L). -Documented history of obesity with confirmation of BMI greater than or equal 30 kg/m2 at Visit 1 (c)High risk of CV disease determined using an established CV risk assessment tool for participants without established CV disease (d)NOTE: The CV risk scoring should be done on a validated scoring system, particularly Q-RISK-3 (score greater than 20%), ASCVD risk equation (score greater than 20%), Framingham risk score (score greater than 20%) or SCORE2/SCORE2-OP. AstraZeneca will also accept other CV risk assessment tools used in the country/region with equivalent risk (high on the scale), provided this is confirmed with the AstraZeneca study team prior to V
- •Documented CV risk assessment done within 6 months of Visit 1 is acceptable. (e)Documented historical CT coronary artery calcification scoring in the setting of either of the following: -greater than or equal to moderate coronary artery calcification score/assessment plus any one other CV risk listed in (b) above -severe/heavy coronary artery calcification score/assessment NOTE:Documented reports of coronary artery calcification scoring based on visual assessment by a radiologist or other individual with appropriate expertise who is qualified to report on such imaging per local practice//guidelines is acceptable and eligibility should be confirmed with AstraZeneca prior to Visit
- •In addition, in cases where the Agatston score is available, the following thresholds can be used: moderate greater than 100 (101 – 1000) and severe/heavy greater than
- •8.Willing and, in the opinion of the investigator, able to adjust current COPD therapy, as required by the protocol. 9.Willing to visit at the study site or participate in virtual visits as required per the protocol to complete all study assessments. Sex and Contraceptive/Barrier Requirements 10.A female is eligible to enter and participate in the study if the female is of: -Non-childbearing potential: either permanently sterilized (hysterectomy, bilateral oophorectomy, bilateral salpingectomy) or who are post-menopausal. A female will be considered post-menopausal if they have been amenorrheic for 12 months prior to the planned date of randomization without an alternative medical cause. The following age- specific requirements apply: -Female less than 50 years old would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatment and follicle-stimulating hormone levels in the post-menopausal range. -Female greater than or equal 50 years old would be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment. -Childbearing potential: has a negative serum pregnancy test at Visit 1 and must use one highly effective form of birth control. A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly. At enrollment, women of childbearing potential who are sexually active with a non-sterilized male partner should be stable on their chosen method of highly effective birth control, as defined below, and willing to remain on birth control until at least 14 days after last dose of study intervention. Cessation of contraception after this point should be discussed with a responsible physician. -Highly effective birth control methods include: -sexual abstinence as defined as complete abstinence from intercourse when it is the preferred and usual lifestyle of the participant.
- •contraceptive subdermal implant.
- •intrauterine device or intrauterine system.
- •oral contraceptive (combined or progesterone only).
- •injectable progestogen.
- •contraceptive vaginal ring.
- •percutaneous contraceptive patches.
- •Male partner sterilization.
- •bilateral tubal ligation 11.Capable of giving signed informed consent.
排除标准
- •Participants are excluded from the study if any of the following criteria apply: Medical Conditions 1 Active diagnosis of asthma within the past 5 years (previous diagnosis as a child or adolescent are eligible), asthma-COPD overlap, or any other chronic respiratory disease other than COPD such as alpha-1 antitrypsin deficiency, active tuberculosis, lung fibrosis, sarcoidosis, interstitial lung disease, and pulmonary hypertension. 2 End-stage renal disease requiring renal replacement therapy or eGFR less than 20 mL/min/1.73 m
- •3 History of heart or lung transplant or actively listed for heart or lung transplant. 4 Implanted left ventricular assist device or implant anticipated in less than 3 months. 5 History of lung cancer and/or treatment for lung cancer within the 5 years prior to Visit
- •6 Unstable or life-threatening cardiac disease – participants with any of the following at Visit 1 would be excluded: (a) An MI or unstable angina in the last 8 weeks (b) Unstable or life-threatening cardiac arrhythmia requiring intervention in the last 8 weeks. NOTE: Any participant who experiences unstable or life-threatening cardiac disease during the run-in period will be excluded but can be rescreened 8 weeks after the resolution of the event. 7 Pneumonia and/or moderate or severe COPD exacerbation that has not resolved at least 8 weeks prior to Visit 1 Any life-threatening condition, including malignancy, with a life expectancy less than 5 years, other than CV disease or COPD, that might prevent the participant from completing the study. Prior/Concomitant Therapy 9 Use of maintenance ICS treatment within the past 12 months. 10 Unable to abstain from protocol-defined prohibited medications Prior/Concurrent Clinical Study Experience 11 Participation in another clinical study with a study intervention administered in the last 30 days or 5 half-lives, whichever is longer prior to Visit 1 (any other investigational product that is not identified in this protocol is prohibited for use during the duration of the study). 12 Participants with a known hypersensitivity to LAMA, LABA or ICS or any component of the MDI. Other Exclusions 13 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). 14 Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements. 15 Previous randomization in the present study. 16 For females only.
- •currently pregnant (confirmed with positive pregnancy test) or breast- feeding. Lifestyle Considerations 1.1.1 Meals and Dietary Restrictions Participants must be fasting for 9 to 12 hours prior to the blood draw at Visit
- •Participants who have not fasted prior to Visit 1 should return to the clinic to have the blood draw performed within 3 business days. 1.1.2 Caffeine, Alcohol, and Tobacco Participants must abstain from ingesting caffeine- or xanthine-containing products (eg, coffee, tea, cola drinks, and chocolate) for 6 hours prior to spirometry testing (assessed at Visit 1). Participants are required to refrain from smoking (including electronic cigarettes) for at least 4 hours prior to spirometry testing. Participants must abstain from consuming any intoxicants within 24 hours before spirometry testing. 1.1.3 Activity Participants should avoid engaging in strenuous exertion for at least 30 minutes prior to spirometry. 1.1.4 Illicit Drugs or Drugs of Abuse Illicit drugs or drugs of abuse will not be allowed from Visit 1 to the end of the follow-up visit or whenever the participant withdraws from the study. If any illicit drugs or drugs of abuse are used by the participant during the study, the dates of use and the amount will be documented, and the participant will be discontinued from randomized study intervention and withdrawn from the study at the discretion of the investigator.
结局指标
主要结局
Evaluate the effect of BGF MDI 320/14.4/9.6μg compared with GFF MDI 14.4/9.6μg On cardiopulmonary outcomes
时间窗: Time to first severe cardiac or COPD event | The composite primary endpoint comprises time to: | - The first HF acute healthcare visit/hospitalization | - MI hospitalization | - Severe COPD exacerbation | - Cardiopulmonary death
次要结局
- Evaluate the effect of combination triple therapy (BGF MDI 320/14.4/9.6 μg) compared with dual bronchodilator therapy (GFF MDI 14.4/9.6 μg) on moderate/severe COPD exacerbations in a population with COPD not receiving ICS
- Evaluate the effect of combination triple therapy (BGF MDI 320/14.4/9.6 μg)(compared with dual bronchodilator therapy (GFF MDI)
- Evaluate the effect of combination triple therapy (BGF MDI 320/14.4/9.6 μg) compared with dual bronchodilator therapy (GFF MDI 14.4/9.6 μg) on the time to MI hospitalization (or cardiac death) in a population with COPD not receiving ICS.
- Evaluate the effect of combination triple therapy (BGF MDI 320/14.4/9.6 μg) compared with dual bronchodilator therapy (GFF MDI 14.4/9.6 μg) on the time to HF acute healthcare visit/ hospitalization (or cardiac death) in a population with COPD not receiving ICS
研究者
Tapankumar M Shah
AstraZeneca Pharma India Ltd.
研究点 (17)
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