A comparative study for the effects of nifedipine GITS and amlodipine besylate administrated in daytime or at nighttime on recovery of blood pressure rhythm and arterial stiffness in the young and middle-aged subjects with non-dipper hypertension (NARRAS): Design and rationale

Introduction: Hypertensive patients with a blunted or absent nocturnal blood pressure (BP) drop (non-dipper) are associated with arterial stiffening and additional cardiovascular risk. Non-dipper hypertension is prevalent in young and middle-aged adults; but the optimal antihypertensive strategy remains unclear. There is a need to explore the effects of different antihypertensive agents and time of administration on recovery of dipper rhythm and arterial stiffness in this population.

Methods and analysis: NARRAS is a randomised controlled trial (RCT), designed to evaluate the effects of long-acting antihypertensive agents administrated in daytime or at nighttime on BP rhythm restoration and arterial stiffness in young and middle-aged non-dipper hypertensive patients. Participants will be randomly assigned to nifedipine GITS (gastrointestinal therapeutic system) 30 mg or amlodipine besylate 5 mg once daily, either taken in the morning or at night. Subjects will be divided into the following groups: group A. nifedipine administrated in the morning (N-M); B. nifedipine at night (N-N); C. amlodipine in the morning (A-M); D. amlodipine at night (A-N). If BP is not at goal during 4 week's visit, dosage of antihypertensive agents will be doubled. BP is measured via 24-hour ambulatory BP monitoring (ABPM) and arterial stiffness is examined before and after 8 weeks of pharmaceutical intervention. The primary endpoint is the difference of average nighttime systolic BP reduction between nifedipine GITS and amlodipine. The second endpoint is the percentage of restoration of a dipper rhythm at 8 weeks. The potential of nighttime dosing on arterial stiffness is also investigated. A sample size of 120 will have 80% power to detect a 3 mm Hg nighttime systolic BP difference between 2 drugs determined with ABPM.

Conclusions: NARRAS study is the first RCT to evaluate the effects of nifedipine GITS and amlodipine besylate on restoration of dipping rhythm and arterial elasticity, either administrated in the morning or evening, in younger non-dipper hypertensive subjects. The findings of NARRAS are likely to be potential to facilitate new therapeutic strategies for this condition.

Trial registration number: NARRAS was registered in clinicaltrials.gov, NCT02940548.