title: Comparison of efficacy and safety between benidipine and hydrochlorothiazide in fosinopril-treated hypertensive patients with chronic kidney disease: protocol for a randomised controlled trial.
abstract: Co-administration of a diuretic or calcium channel blocker with an ACE inhibitor are both preferred combinations in patients with hypertensive chronic kidney disease (CKD). According to the available evidence, it is still unknown which combination plays a more active role in renal protection. We hypothesised that a combination of fosinopril and benidipine may delay the progression of CKD more effectively than a combination of fosinopril and hydrochlorothiazide (HCTZ).
  
  
  
  This study will be a multicentred, prospective, double-blind, randomised parallel controlled trial for hypertensive CKD patients in China. Patients will be randomised to one of two treatment groups: a combination of benidipine 4-8 mg/day and fosinopril 20 mg/day; or a combination of HCTZ 12.5-25 mg/day and fosinopril 20 mg/day. Patients will be followed up for 24 months after a month's fosinopril run-in. There will be dose-titration after 1 and 2 months. The primary endpoint is changes in estimated glomerular filtration rate (eGFR) from baseline to month 24. Secondary endpoints include changes in home blood pressure (BP), ambulatory BP, proteinuria, urinary albumin/creatinine ratio, and composite renal events in 24 months. Inclusion criteria are: age 18-80 years, non-dialysis CKD patients with eGFR >30 mL/min/1.73 m2, home BP >130 mm Hg systolic or BP >80 mm Hg diastolic at the screening and randomisation, and 24 hour proteinuria <3.5 g. Principal exclusions are hypertensive crisis, transplantation, cancer, severe diabetes complications, hyperkalaemia and severe allergy. The required sample size was 511 patients for detecting a difference in the change of eGFR (one sided α=0.025, power 1-β=0.90).
  
  
  
  BEAHIT (Benidipine and Hydrochlorothiazide in Fosinopril Treated Chronic Kidney Disease Patients with Hypertension) was approved by Changzheng Hospital Ethics Committee (CZ-20160504-16). The outcomes will be published in a peer-reviewed journal.
  
  
  
  NCT02646397.
authors.affiliation: Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, Shanghai, China.|Department of Pharmacy, 309 Hospital of PLA, Beijing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Xue
authors.affiliation: Department of Nephrology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Lv
authors.affiliation: Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Dai
authors.affiliation: Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Shengqiang
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Nephrology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, 309 Hospital of PLA, Beijing, China.
authors.forename: Guanren
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Changlin
authors.initials: C
authors.lastname: Mei
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D002681:China; D004095:Dihydropyridines / Q000008:administration & dosage*; D004232:Diuretics / Q000008:administration & dosage; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D017328:Fosinopril / Q000008:administration & dosage*; D005919:Glomerular Filtration Rate; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage*; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011507:Proteinuria / Q000150:complications; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000503:physiopathology; D012107:Research Design; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D004232:Diuretics; D006852:Hydrochlorothiazide; C061004:benidipine; D017328:Fosinopril
keywords: glomerular filtration rate