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

Introduction 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). Methods and analysis 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 20mg/day; or a combination of HCTZ 12.5-25mg/day and fosinopril 20mg/day. Patients will be followed up for 24months after a month's fosinopril run-in. There will be dose-titration after 1 and 2months. 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 24months. Inclusion criteria are: age 18-80years, non-dialysis CKD patients with EGFR >30mL/min/1.73m 2, home BP >130mmHg systolic or BP >80mmHg diastolic at the screening and randomisation, and 24hour proteinuria <3.5g. 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). Ethics and dissemination 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. Trial registration number NCT02646397.