Benidipine and Hydrochlorothiazide in Fosinopril Treated Chronic Kidney Disease Patients With Hypertension

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Comparison of Efficacy and Safety Between Benidipine and Hydrochlorothiazide in Fosinopril Treated Chronic Kidney Disease Patients With Hypertension: a Randomized Controlled Trial

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Drug: Fosinopril
* Drug: Benidipine
* Drug: Hydrochlorothiazide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fosinopril,benidipine combination<br>254 CKD patients with HTN will take oral tablets of fosinopril (20 mg) plus benidipine (4/8 mg）once daily for 6 months. | Drug: Fosinopril<br>* Fosinopril is an angiotensin-converting enzyme inhibitor.<br>* Other names: Fosinil;Drug: Benidipine<br>* Benidipine is a dihydropyridine-derived calcium channel blocker.<br>* Other names: benidipine hydrochloride;|
| Experimental: Fosinopril,hydrochlorothiazide combination<br>254 CKD patients with HTN will take oral tablets of fosinopril (20 mg) plus hydrochlorothiazide (12.5/25 mg）once daily for 6 months. | Drug: Fosinopril<br>* Fosinopril is an angiotensin-converting enzyme inhibitor.<br>* Other names: Fosinil;Drug: Hydrochlorothiazide<br>* Hydrochlorothiazide is a diuretic medication.<br>* Other names: HydroDIURIL;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in estimated glomerular filtration rate |  | Changes in eGFR at month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abnormal renal events | Number of participants with 30% reduction of eGFR, doubling of serum creatinine concentration,end-stage renal disease (eGFR< 15 mL/min/1.73m²) or chronic dialysis. | 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 | Number of participants with cardiovascular morbidity (nonfatal stroke, non-fatal myocardial infarction, resuscitated sudden cardiac death, unstable angina; and coronary revascularization procedures) and cardiovascular mortality (death due to sudden cardiac death, fatal stroke, fatal myocardial infarction, congestive heart failure or other cardiovascular causes). | At month 6 | 
| Adverse Events | Number of participants with abnormal laboratory values and/or adverse events that are related to Treatment | From baseline to month 6 | 
| Changes in urinary albumin excretion |  | From baseline to month 6 | 
| Changes in mean DBP |  | From baseline to month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glomerular filtration rate, hypertension