Efficacy Evaluation of Glimepiride in Patients With Type 2 Diabetes Mellitus and Chronic Heart Failure With Reduced Ejection Fraction: A Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial.
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 1,484
- 试验地点
- 1
- 主要终点
- A composite endpoint of cardiovascular death, heart transplantation, or worsening heart failure (defined as rehospitalization for heart failure or an emergency heart failure visit requiring intravenous therapy).
研究概览
简要总结
Evaluating the safety and efficacy of glimepiride in patients with type 2 diabetes and chronic heart failure with reduced ejection fraction--a multicenter randomized controlled study.
详细描述
Diabetes and heart failure share common pathophysiological mechanisms. The synergistic effects of managing both conditions, along with the potential for diabetes treatment to modulate the risk of heart failure outcomes, hold significant medical promise.Currently, the relationship between sulfonylureas，primarily including glimepiride, and heart failure outcomes remains poorly understood, with ongoing controversy regarding their cardiovascular effects in observational studies. No large-scale, randomized controlled trials have yet been conducted to validate the impact of sulfonylureas on patients with established heart failure. Our prospective cohort studies have preliminarily confirmed the cardioprotective effects of glimepiride in patients with type 2 diabetes complicated by chronic heart failure, demonstrating a favorable safety profile. Therefore, this study aims to conduct a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the therapeutic efficacy of glimepiride in patients with type 2 diabetes complicated by chronic heart failure.This study plan aims to recruit 1,484 eligible participants, who will be randomly assigned in a 1:1 ratio to either the glimepiride group or the placebo group. The total study duration is 36 months, with all participants required to complete baseline visits and outpatient follow-ups at months 1, 3, 6, 9, 12, 18, 24, 30 and 36.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This study employed a double-blind design, meaning that neither the patients, investigators, study coordinators, members of the endpoint adjudication committee, nor the data analysts were aware of the specific group assignments.
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 between 18 and 80 years old at the time of enrollment; gender is not restricted.
- •Patients diagnosed with type 2 diabetes according to the "Chinese Diabetes Prevention and Management Guidelines (2024 Edition)" issued by the Chinese Medical Association Diabetes Branch, with a confirmed diagnosis at least three months prior.
- •According to the "Chinese Guidelines for the Diagnosis and Treatment of Heart Failure (2024 Edition)" issued by the Chinese Society of Cardiology, the diagnosis is heart failure with reduced ejection fraction (HFrEF) or heart failure with mildly reduced ejection fraction (HFmrEF), confirmed at least three months prior.
- •NYHA heart failure classification stage II-IV;
- •Within 12 months prior to enrollment, left ventricular ejection fraction (LVEF) was < 50%, as determined by echocardiography, nuclear ventriculography, angiography, or cardiac magnetic resonance imaging.
- •NT-proBNP levels ≥ 600 pg/mL in patients with no recent hospitalization for heart failure; NT-proBNP levels ≥ 400 pg/mL within the past 12 months due to heart failure hospitalization; NT-proBNP levels ≥ 900 pg/mL in patients with heart failure complicated by atrial fibrillation/flutter.
- •Patients must have experienced stable heart failure symptoms for at least three months prior to enrollment and must have received standardized chronic heart failure therapy and guideline-directed diabetes management for no less than two weeks before enrollment, with no dose adjustments during this period.
- •Participation is voluntary and requires signing an informed consent form; follow-up can extend beyond three years.
排除标准
- •Heart failure caused by valvular disease, congenital heart conditions, pericardial diseases, arrhythmias, or non-cardiogenic illnesses; as well as heart failure resulting from failure of vital organs such as renal or hepatic failure; and right-sided heart failure due to pulmonary origin or other definitive causes.
- •Currently experiencing acute decompensated heart failure (ADHF) or hospitalized for ADHF within the previous four weeks before enrollment.
- •Patients scheduled to undergo coronary artery revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or cardiac resynchronization therapy following randomization, or who have received cardiac resynchronization therapy within 12 weeks prior to enrollment.
- •Any conditions other than cardiovascular diseases, including but not limited to malignancies with an expected survival of less than three years, severe mental disorders, hematologic diseases, neuroendocrine disorders, elevated liver transaminases and alkaline phosphatase levels exceeding three times the upper limit of normal (ULN), renal impairment indicated by serum creatinine greater than 2 mg/dL (176.82 µmol/L), and hyperkalemia with serum potassium levels exceeding 5.5 mmol/L.
- •Chronic kidney disease stage 3b or more advanced renal impairment (i.e., estimated glomerular filtration rate [eGFR]/creatinine clearance [CrCl] <45 ml/min);
- •Left ventricular outflow tract obstruction, acute or fulminant myocarditis, aortic aneurysm, aortic dissection, or significant hemodynamic changes caused by unrepaired valves;
- •Cardiac shock, uncontrollable malignant arrhythmias, second-degree or higher sinus or atrioventricular block without pacemaker therapy, progressive unstable angina pectoris, or acute myocardial infarction;
- •Uncontrolled hypertension with systolic blood pressure (SBP) ≥180 mmHg and/or diastolic blood pressure (DBP) ≥110 mmHg; or SBP <90 mmHg and/or DBP <60 mmHg;
- •Female patients who are pregnant, planning to become pregnant, or breastfeeding;
- •Patients who have participated in any other investigational medicinal product clinical trial within the past 4 weeks;
- •Patients with a history of allergies or hypersensitivity to glimepiride or its derivatives;
- •Received glimepiride treatment within 8 weeks prior to enrollment or previously demonstrated intolerance to glimepiride;
- •Patients refusing to comply with study requirements to complete the research;
- •Conditions where the investigator deems the patient unable to understand and/or comply with study medications, procedures, or any other circumstances that may prevent completion of the study;
- •Any other reason deemed inappropriate for inclusion by the study physician.
研究组 & 干预措施
Glimepiride group
Standardized treatment for chronic heart failure + standardized treatment for type 2 diabetes + oral glimepiride (initial oral dose is 2 mg once daily. After 4 weeks, adjust the oral dose based on glycemic control and tolerability: If glycemic control is adequate, maintain the initial oral dose. If glycemic control is inadequate, modify the oral dose to 4 mg once daily.)
干预措施: Glimepiride (oral) (Drug)
Placebo group
Standardized treatment for chronic heart failure + standardized treatment for type 2 diabetes + oral placebo (equivalent placebo administered according to the same regimen)
干预措施: Placebo (Drug)
结局指标
主要结局
A composite endpoint of cardiovascular death, heart transplantation, or worsening heart failure (defined as rehospitalization for heart failure or an emergency heart failure visit requiring intravenous therapy).
时间窗: 3 years
The Primary Outcome is defined as a composite endpoint consisting of the time to the first occurrence of any of the following events: 1. Cardiovascular death is defined as any death due to a direct cardiovascular cause. 2. Heart transplantation is defined as receiving an allogeneic in situ heart transplant due to end-stage heart failure. The event date is defined as the date of surgery. 3. Heart failure exacerbation is defined as requiring intensive treatment due to worsening symptoms and signs of heart failure, meeting any of the following criteria: ① readmission for heart failure; ② urgent heart failure visit requiring intravenous therapy.
次要结局
- Rehospitalization due to heart failure(3 years)
- All-cause mortality rate(3 years)
- Cardiovascular death, heart transplantation, or readmission due to heart failure(3 years)
- Cardiovascular death, heart transplantation(3 years)
- Incidence of discontinuing treatment due to worsening heart failure(3 years)
- Rate of successful resuscitation following cardiac arrest(3 years)
- Incidence of malignant arrhythmias(3 years)
- Rate of serum NT-proBNP decrease(3 years)
- Changes in Kansas Cardiomyopathy Questionnaire (KCCQ) scores(3 years)
- Changes in 6-Minute Walk Test (6MWT) Results(3 years)
- Incidence of non-fatal myocardial infarction or non-fatal stroke(3 years)