Clinical trial NCT02646397: Benidipine and Hydrochlorothiazide in Fosinopril Treated Chronic Kidney Disease Patients With Hypertension
Official title: Comparison of Efficacy and Safety Between Benidipine and Hydrochlorothiazide in Fosinopril Treated Chronic Kidney Disease Patients With Hypertension: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Kidney Disease
Keywords: glomerular filtration rate
hypertension
Lead sponsor: Shanghai Changzheng Hospital
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital of Zhejiang University
name: Zhongda Hospital
name: Ruijin Hospital
name: The First Affiliated Hospital of Zhengzhou University
name: Sichuan Provincial People's Hospital
name: The Second Affiliated Hospital of Dalian Medical University
name: The First Affiliated Hospital of Anhui Medical University
First posted: 2016-01-05
Enrollment: 508
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. 24 h proteinuria \< 1.5g at the enrollment
3. Patients who signed the informed consent form
4. Baseline serum Cr \< 3 mg/dL at the enrollment and randomization

Exclusion Criteria:

1. Hypertensive crisis (SBP \> 180 mmHg and/or DBP\>110 mmHg)
2. Refractory hypertension (taking \> 2 antihypertensive drugs more than a month, SBP still \> 160mm Hg or DBP \> 100mmHg)
3. Baseline serum Cr \> 3 mg/dl, or kidney transplantation
4. 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.
5. Patients diagnosed as cancer or severe sepsis
6. Hematological system disorders: myelodysplastic syndrome, granulocytopenia, hypereosinophilic syndrome, polycythemia, thrombocytopenia, and et al.
7. Restrictive pericarditis
8. Systemic Lupus Erythematous
9. Severe diabetes complications such as diabetic ketoacidosis, hyperosmolar coma, retinopathy, amputation, and et al.
10. Patients diagnosed as hyperkalemia(\>5.5mmol/L) within 6 months or at the enrollment
11. Renal artery stenosis or vascular embolism disease
12. Patient is currently pregnant or lactational
13. AST/ALT \> three times of the upper limit of standard value at the baseline
14. Any severe allergy of CCB, diuretic or ACE inhibitor
15. History of severe side effects of CCB, diuretic or ACE inhibitor; long-term use of non-steroidal anti-inflammatory drugs
16. Use of other investigational drugs within 30 days or 5 half-lives of last visit, whichever is longer.
17. Other unsuitable patients judged by the investigators

Primary outcomes:
measure: Changes in estimated glomerular filtration rate
timeFrame: Changes in eGFR at month 6
Secondary outcomes:
measure: Abnormal renal events
timeFrame: From baseline to month 6
measure: Changes in 24 hour proteinuria
timeFrame: From baseline to month 6
measure: Changes in mean SBP
timeFrame: From baseline to month 6
measure: Abnornal cardiovascular events
timeFrame: At month 6
measure: Adverse Events
timeFrame: From baseline to month 6
measure: Changes in urinary albumin excretion
timeFrame: From baseline to month 6
measure: Changes in mean DBP
timeFrame: From baseline to month 6
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Nephrology, Shanghai Changzheng Hospital
state: Shanghai
Study officials:
affiliation: Division of Nephrology, Shanghai ChangZheng Hospital
name: Changlin Mei
role: STUDY_CHAIR
References:
citation: Xue C, Zhou C, Yang B, Lv J, Dai B, Yu S, Wang Y, Zhao G, Mei C. Comparison of efficacy and safety between benidipine and hydrochlorothiazide in fosinopril-treated hypertensive patients with chronic kidney disease: protocol for a randomised controlled trial. BMJ Open. 2017 Feb 24;7(2):e013672. doi: 10.1136/bmjopen-2016-013672.