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

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

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.

Study Overview

• Status: Unknown
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Drug: Fosinopril; Drug: Benidipine; Drug: Hydrochlorothiazide

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.

• Study Type: Interventional
• Enrollment (Anticipated): 508
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200003
      • Department of Nephrology, Shanghai Changzheng Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Fosinopril; Fosinopril is an angiotensin-converting enzyme inhibitor.; Other Names: Fosinopril Sodium; Squibb Brand of Fosinopril Sodium; Fosinil; Drug: Benidipine; Benidipine is a dihydropyridine-derived calcium channel blocker.; Other Names: benidipine hydrochloride
Experimental: 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.	Drug: Fosinopril; Fosinopril is an angiotensin-converting enzyme inhibitor.; Other Names: Fosinopril Sodium; Squibb Brand of Fosinopril Sodium; Fosinil; Drug: Hydrochlorothiazide; Hydrochlorothiazide is a diuretic medication.; Other Names: HCTZ; Dichlothiazide; HydroDIURIL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Shanghai Changzheng Hospital
• Collaborators: The First Affiliated Hospital of Anhui Medical University; Ruijin Hospital; First Affiliated Hospital of Zhejiang University; The First Affiliated Hospital of Zhengzhou University; Zhongda Hospital; Sichuan Provincial People's Hospital; The Second Affiliated Hospital of Dalian Medical University
• Investigators: Study Chair: Changlin Mei, Division of Nephrology, Shanghai ChangZheng Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: December 29, 2015
• First Submitted That Met QC Criteria: December 31, 2015
• First Posted (Estimate): January 5, 2016

Study Record Updates

• Last Update Posted (Estimate): January 5, 2016
• Last Update Submitted That Met QC Criteria: December 31, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: hypertension; glomerular filtration rate
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Urologic Diseases; Renal Insufficiency; Hypertension; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Enzyme Inhibitors; Protease Inhibitors; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin-Converting Enzyme Inhibitors; Sodium Chloride Symporter Inhibitors; Hydrochlorothiazide; Fosinopril; Benidipine
• Other Study ID Numbers: CZKI-CKD-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided