Bedtime ACEIs/ARBs Versus Morning ACEIs/ARBs for Reverting Non-dipping Hypertension

Is Bedtime Administration of ACEIs and ARBs More Effective for Reverting Non-dipper Status Than Morning Administration for Non-dipping Hypertension in Hong Kong Primary Care? A Pilot Study

Background: Non-dipping (ND), defined as a <10% decrease in blood pressure (BP) during sleep, is an independent significant predictor of cardiovascular outcome in hypertensive patients. A few anti-hypertensive medications, including angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs), may normalize dipping if administered at night. Chinese data are scarce and there are no prospective studies on cardiovascular outcomes in Chinese patients.

Aim: To determine if the bedtime administration of ACEIs and ARBs is more effective at normalizing ND than morning administration. As a pilot project, the feasibility of recruiting hypertension patients in primary care for ambulatory blood pressure monitoring (ABPM) and conducting a clinical trial will be evaluated such that future larger randomized trials can be planned to determine treatments for ND.

Method: Fifty patients diagnosed with essential hypertension who are receiving either ACEIs or ARBs and diagnosed with ND will be randomized to take ACEIs or ARBs either early morning or before bedtime. A follow-up 48-hour ABPM will be performed after 4-6 weeks to examine post-treatment changes in BP and ND status.

Outcome: The primary outcome of this proposed study is the proportion of ND at 6 weeks; secondary outcomes will include (i) mean awake and asleep SBP/DBP of 48-hour duration (ii) feasibility of this pilot study will be assessed by recruitment and dropout rates during the study period.

Potential: This pilot study will provide the basis for a future larger randomized controlled study to further examine the treatment for ND in primary care.

Study Overview

• Status: Terminated
• Conditions: Hypertension; Non-Dipping
• Intervention / Treatment: Drug: ACEi, ARB

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 4

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Lek Yuen Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who are taking an ACEI or an ARB
• >18 years of age
• Chinese and
• Received a diagnosis of primary HT.

Exclusion Criteria:

• Severe HT as defined by a clinic systolic BP ≥180 mmHg and/or diastolic BP ≥ 110 mmHg
• allergic reaction or intolerance to the current ACEI or ARB
• unable to provide consent
• pregnancy
• night-time worker
• occupational drivers since patients will be asked not to move during BP measurements, which may induce potential danger in driving
• taking anti-coagulants to avoid causing bruises when using ABPM
• known atrial fibrillation since ABPM use has not been validated in this group
• known hyperkalemia
• ABPM discovered hypotension (mean SBP < 100 and/or mean DBP < 60) because these patients may need to stop their medications
• Reported sleep time of <4 hours per night (at least seven readings are recommended during sleep for an ABPM recording to be valid, and a sleeping time < 4 hours is unlikely to generate valid results).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: intervention; ACEIs or ARBs will be switch to be taken before bedtime	Drug: ACEi, ARB; To take the ACEis or ARBs before bedtime instead of in the morning
ACTIVE_COMPARATOR: control; ACEIs or ARBs will be taken in the morning as usual	Drug: ACEi, ARB; To take the ACEis or ARBs before bedtime instead of in the morning

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of non-dipping in each group as measured by ambulatory BP machines(ABPM)	the ABPM - An ApneABP (Meditech, Hungary) will be used in the study. non-dipping is defined as lack of more than 10% drop in SBP during sleep when compared to awake BP. The sleep duration and time are defined by actigraphy (Actigraph, model GT9X-BT)	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mean awake and asleep SBP/DBP of 48-hour duration as assessed by ABPM		6 weeks
feasibility of the intervention as assessed by dropout rate	The trial is deemed feasible and a larger similar study can be conducted if: (i) ≤30% of ND patients drop out from the study	1 year (assessed after the whole study)

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2017
• Primary Completion (ACTUAL): December 31, 2019
• Study Completion (ACTUAL): December 31, 2019

Study Registration Dates

• First Submitted: September 13, 2017
• First Submitted That Met QC Criteria: September 13, 2017
• First Posted (ACTUAL): September 15, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 8, 2020
• Last Update Submitted That Met QC Criteria: April 7, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: 2017.182-T

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: to decide after end of trial

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No