Comparison of Efficacy and Safety Between Benidipine and Hydrochlorothiazide in Fosinopril Treated Chronic Kidney Disease Patients With Hypertension: a Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 入组人数
- 508
- 试验地点
- 1
- 主要终点
- Changes in estimated glomerular filtration rate
研究概览
简要总结
The purpose of this study is to compare the effect of fosinopril plus benidipine vs. fosinopril plus hydrochlorothiazide on the renal function during the 6-month treatment in CKD patients with HTN.
详细描述
Patients with chronic kidney dysfunction or injury which affected the health over three months were diagnosed with chronic kidney disease (CKD).China has a high prevalence of CKD.The prevalence, awareness, and treatment of hypertension (HTN) in non-dialysis CKD patients were 67.3%,85.8%, and 81.0%, respectively. The renin-angiotensin system inhibitors (RASI) including angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II type 1 receptor blocker (ARB) have been deeply confirmed to have apparent reno-protective effect in patients with CKD.Co-administration of diuretics and calcium channel blockers (CCBs) with ACEIs or ARBs are the most common combinations. Hydrochlorothiazide plus RASIs are another widely used combination according to the synergetic function of antihypertensive action and offset mutual adverse effects. Until now, no large scale studies have compared the effect of initial treatment with two different combinations of antihypertensive drugs in CKD patients on the progression of kidney disease in China. Studies in the subsets of CKD (diabetes and non-diabetes, micro-albuminuria and macro-albuminuria) are urgently needed.We aimed to conduct a large scale study to compare L/T-type CCB and diuretic on the basis of ACEI in CKD with HTN on renal progression of CKD in China.
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
- None
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
- •Patients diagnosed with non-dialysis CKD at the enrollment and randomization eGFR≥ 30 ml/min per 1.73 m2 at the enrollment and randomization SBP> 130 mmHg and/or DBP > 80 mmHg at the enrollment and randomization. Patients could not receive more than two antihypertensive medications prior to our enrollment, and should discontinue the prior antihypertensive medications after the enrollment according to the investigators' advice.
- •24 h proteinuria < 1.5g at the enrollment
- •Patients who signed the informed consent form
- •Baseline serum Cr < 3 mg/dL at the enrollment and randomization
排除标准
- •Hypertensive crisis (SBP > 180 mmHg and/or DBP>110 mmHg)
- •Refractory hypertension (taking > 2 antihypertensive drugs more than a month, SBP still > 160mm Hg or DBP > 100mmHg)
- •Baseline serum Cr > 3 mg/dl, or kidney transplantation
- •Patients diagnosed as severe cardiac arrhythmia (severe extra beats, supraventricular tachycardias, ventricular arrhythmias, or bradyarrhythmias), heart failure, NYHA >Ⅲ, angina, stroke, left ventricular hypertrophy or myocardial infarction within 12 months prior to first visit.
- •Patients diagnosed as cancer or severe sepsis
- •Hematological system disorders: myelodysplastic syndrome, granulocytopenia, hypereosinophilic syndrome, polycythemia, thrombocytopenia, and et al.
- •Restrictive pericarditis
- •Systemic Lupus Erythematous
- •Severe diabetes complications such as diabetic ketoacidosis, hyperosmolar coma, retinopathy, amputation, and et al.
- •Patients diagnosed as hyperkalemia(>5.5mmol/L) within 6 months or at the enrollment
- •Renal artery stenosis or vascular embolism disease
- •Patient is currently pregnant or lactational
- •AST/ALT > three times of the upper limit of standard value at the baseline
- •Any severe allergy of CCB, diuretic or ACE inhibitor
- •History of severe side effects of CCB, diuretic or ACE inhibitor; long-term use of non-steroidal anti-inflammatory drugs
- •Use of other investigational drugs within 30 days or 5 half-lives of last visit, whichever is longer.
- •Other unsuitable patients judged by the investigators
研究组 & 干预措施
Fosinopril,benidipine combination
254 CKD patients with HTN will take oral tablets of fosinopril (20 mg) plus benidipine (4/8 mg）once daily for 6 months.
干预措施: Fosinopril (Drug)
Fosinopril,benidipine combination
254 CKD patients with HTN will take oral tablets of fosinopril (20 mg) plus benidipine (4/8 mg）once daily for 6 months.
干预措施: Benidipine (Drug)
Fosinopril,hydrochlorothiazide combination
254 CKD patients with HTN will take oral tablets of fosinopril (20 mg) plus hydrochlorothiazide (12.5/25 mg）once daily for 6 months.
干预措施: Fosinopril (Drug)
Fosinopril,hydrochlorothiazide combination
254 CKD patients with HTN will take oral tablets of fosinopril (20 mg) plus hydrochlorothiazide (12.5/25 mg）once daily for 6 months.
干预措施: Hydrochlorothiazide (Drug)
结局指标
主要结局
Changes in estimated glomerular filtration rate
时间窗: Changes in eGFR at month 6
次要结局
- Changes in urinary albumin excretion(From baseline to month 6)
- Abnormal renal events(From baseline to month 6)
- Changes in 24 hour proteinuria(From baseline to month 6)
- Changes in mean SBP(From baseline to month 6)
- Abnornal cardiovascular events(At month 6)
- Adverse Events(From baseline to month 6)
- Changes in mean DBP(From baseline to month 6)
研究者
Changlin Mei
Professor, Director of Division of Nephrology
Shanghai Changzheng Hospital