A Multicentre, Randomised, Double-blind, Placebo-controlled Phase III Study, Evaluating the Effect of Dapagliflozin on Prevention of Cardiotoxicity in Breast Cancer Patients Undergoing Anthracycline-based Chemotherapy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 188
- 试验地点
- 3
- 主要终点
- Primary efficacy composite endpoint (cancer therapeutics related cardiac dysfunction) at 12 months.
研究概览
简要总结
The purpose of this study is to evaluate the effect of dapagliflozin on the incidence of cancer therapeutics-related cardiac dysfunction in patients with breast cancer receiving anthracycline treatment.
详细描述
This is a multicentre, randomised, double-blind, placebo-controlled phase III study, evaluating the effect of dapagliflozin versus placebo on prevention of cardiotoxicity in breast cancer patients undergoing anthracycline-based chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 years and < 80 years.
- •Diagnosis of invasive breast cancer [stage I-III] and planned anthracycline treatment within 60 days.
- •Signed Informed Consent to participate in the study.
排除标准
- •Urinary tract infection with the need for treatment with an antibiotic 48 hours before the scheduled start of anthracycline treatment.
- •Recognised heart failure or symptoms which, in the opinion of the investigator may be a symptom of undiagnosed heart failure.
- •Left ventricular ejection fraction < 50% at the time of the screening.
- •Severe valvular heart disease.
- •A history of clinically significant arrhythmia, including atrial fibrillation regardless of type (at discretion of the investigator).
- •A history of stroke.
- •Cardiomyopathy: congenital, post-inflammatory, toxic, infiltrative (e.g. amyloidosis, sarcoidosis, haemochromatosis), postnatal or hypertrophic.
- •Pulmonary hypertension.
- •Uncontrolled arterial pressure or systolic pressure < 80 mmHg at screening (at the discretion of the investigator).
- •BMI > 40 kg/m
- •Diagnosed type 1 or type 2 diabetes or fasting glucose ≥ 126 mg/dl or HbA1C ≥ 6,5% (48 mmol/mol).
- •Pregnancy or breastfeeding.
- •Lack of compliance to use highly effective method of birth control.
- •Expected or possible treatment with epirubicin or liposomal doxorubicin within 12 months.
- •Taking another study drug or drugs from the group of SGLT2 inhibitors up to 6 months before the screening visit.
- •Taking semaglutide, liraglutide and metformin during the 30 days preceding the screening visit.
- •eGFR < 25 ml/min/1.73m2 according to CKD EPI.
- •Life expectancy < 12 months or cancer disease stage IV according to the TNM classification.
- •Alanine transaminase or aspartate transaminase levels above 2.5 times the local norm.
- •Anemia with Hemoglobin < 9 g/dl.
- •Kidney failure > G2 (according to KDIGO classification).
- •Liver disorders, Child-Pugh score >
- •Known, active infections with HIV, HBV, HCV, tuberculosis.
- •Any other condition which, in the opinion of the investigator, makes it impossible to fulfill the requirements for participation in this study.
研究组 & 干预措施
Dapagliflozin
Dapagliflozin 10 mg tablet orally once daily for 12 months
干预措施: Dapagliflozin (Drug)
Placebo
Placebo tablet matching dapagliflozin orally once daily for 12 months
干预措施: Placebo (Drug)
结局指标
主要结局
Primary efficacy composite endpoint (cancer therapeutics related cardiac dysfunction) at 12 months.
时间窗: 12 months
Incidence of cancer therapeutics related cardiac dysfunction defined as: 1. the appearance of heart failure symptoms (NYHA class I-IV) due to an impairment of heart function or structure within 12 months; or 2. asymptomatic decrease in left ventricular ejection fraction \> 10% after 12 months; or 3. asymptomatic decrease in left ventricular ejection fraction \< 10% but up to 40-49% after 12 months; or 4. asymptomatic decrease in global left ventricular longitudinal strain \>15% after 12 months; or 5. asymptomatic increase in biomarkers (troponin I \> upper reference limit (99th centile) and increase of at least 30% from pre-treatment concentration or NTproBNP \> 125 pg/ml and increase of at least 30% from baseline) after 12 months.
次要结局
- Secondary efficacy composite endpoint (cancer therapeutics related cardiac dysfunction) at 6 months.(6 months)
- Change in left ventricular ejection fraction at 6 and 12 months.(6 and 12 months)
- Change in Troponin I after 6 and 12 months.(6 and 12 months)
- Composite endpoint of cardiovascular events.(13 months (additional 1 month of safety follow-up after end of treatment).)
- Occurrence of death from any cardiovascular reasons.(13 months (additional 1 month of safety follow-up after end of treatment).)
- Occurrence of non-fatal stroke.(13 months (additional 1 month of safety follow-up after end of treatment).)
- Occurrence of renal failure.(13 months (additional 1 month of safety follow-up after end of treatment).)
- Occurrence of allergic reactions.(13 months (additional 1 month of safety follow-up after end of treatment).)
- Occurrence of death from any cause.(13 months (additional 1 month of safety follow-up after end of treatment).)
- Occurrence of ionic disorders.(13 months (additional 1 month of safety follow-up after end of treatment).)
- Change in left ventricular diastolic function at 6 and 12 months.(6 and 12 months)
- Change in NTproBNP levels at 6 and 12 months.(6 and 12 months)
- Quality of life at 6 and 12 months assessed using the five-dimensional EQ-5D questionnaire.(6 and 12 months)
- Occurrence of non-fatal myocardial infarction.(13 months (additional 1 month of safety follow-up after end of treatment).)
- Occurrence of hypersensitivity to investigated drug.(13 months (additional 1 month of safety follow-up after end of treatment).)
- Occurrence of hypoglycaemia.(13 months (additional 1 month of safety follow-up after end of treatment).)
- Occurrence of infection.(13 months (additional 1 month of safety follow-up after end of treatment).)