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RecruitingNCT05089448Updated Jan 6, 2025

Morning Versus Bedtime Dosing of Antihypertensive Medication

A Phase 4 interventional study of Alisartan, Amlodipine besylate and Alisartan, Amlodipine besylate in Hypertension, Blood Pressure and Drug Use, sponsored by Yan Li. Recruiting at 1 site in China. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2025-01-06.

Sponsored by Yan Li · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
300
Allocation
Randomized
Ages
18 Years to 70 Years
Sex
All
01

Study summary

Previous studies have shown that elevated nighttime blood pressure (BP) was more closely associated with cardiovascular mortality and morbidity than daytime and clinic BPs. With increasingly advanced technology, not only 24-hour ambulatory but also home BP monitors can be used to evaluate nighttime BP. The validation study of the Omron HEM 9601T showed that the wrist-type home BP monitor could be a suitable and reliable tool for the diagnosis and management of nocturnal hypertension. However, up to now, there is no data on home nighttime BP in Chinese patients and it is unclear if different dosing time would reduce ambulatory and home nighttime BPs differently.

The investigators therefore designed a multicenter randomized clinical trial to compare between morning dosing and bedtime dosing of antihypertensive medications in the difference in nighttime, daytime and the 24-h BP reductions evaluated by both ambulatory and home BP monitoring, and in target organ protections.

02

Conditions studied

  • Hypertension
  • Blood Pressure
  • Drug Use

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03

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Male or female patients aged 18-70 years old;
  2. Never treated for hypertension or stopped using antihypertensive drugs for at least 2 weeks;
  3. In the two screenings,the clinical systolic BP should be in the range of 140-159 mmHg, the diastolic BP \< 100 mmHg;
  4. The average 24-hour systolic BP ≥130mmHg, daytime systolic BP ≥ 135 mmHg, and nighttime systolic BP ≥ 120 mmHg;
  5. The average of bilateral brachial-ankle pulse wave velocity ≥14m/s;
  6. Be willing to participate in the trial, sign the informed consent form, and be able to visit doctors by himself or herself.

Exclusion criteria

Exclusion Criteria:

  1. Secondary hypertension;
  2. Concomitant obstructive sleep apnea (STOP-BANG score ≥ 5), insomnia, Parkinson's syndrome, or nocturnal polyuria and other diseases that affect nighttime BP;
  3. Need to work at night;
  4. Ambulatory BP monitoring was invalid (\<70% valid readings, or \<20 daytime readings or \<7 nighttime readings);
  5. Concomitant diseases that need taking medications influencing BP;
  6. Coronary heart disease, myocardial infarction or stroke within recent 6 months;
  7. Atrial fibrillation or frequent arrhythmia;
  8. Abnormal liver function exemplified as an increased alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBL) over the double of the upper limit of normal range; abnormal renal function exemplified as a serum creatinine ≥176 µmol/L; and plasma potassium ≥5.5 mmol/L or ≤3.5mmol/L;
  9. Pregnant or lactating women;
  10. Contraindications of angiotensin II receptor blocker or calcium channel blocker;
  11. Other concomitant diseases which are considered not suitable to participate in the trial, such as thyroid diseases, acute infectious diseases, chronic mental diseases, tumor, etc.
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
300 participants (estimated)

Study arms

  • Active comparator
    The morning dosing group

    After randomization, subjects will take alisartan 120 mg (Salubris, Shenzhen, China) once daily at 6:00-10:00. After 8 weeks of treatment, if the 24-hour ambulatory systolic BP remained ≥ 130 mmHg, alisartan will be doubled to 240mg. After 16 weeks of treatment, if the 24-hour ambulatory systolic BP remained ≥ 130 mmHg, amlodipine besylate 2.5 mg (Dawnrays, Suzhou, China) once daily will be added. The whole treatment duration will last for 24 weeks.

    Drug: Alisartan, Amlodipine besylate

  • Experimental
    The bedtime dosing group

    After randomization, subjects will take alisartan 120 mg once daily at 20:00-24:00. The follow-up plan is the same as the morning dosing group.

    Drug: Alisartan, Amlodipine besylate

Interventions

  • DrugAlisartan, Amlodipine besylate

    Drugs will be taken once daily at 6:00-10:00.

  • DrugAlisartan, Amlodipine besylate

    Drugs will be taken once daily at 20:00-24:00.

05

What researchers measure

Primary outcomes

  1. Nighttime systolic BP reduction in mmHg

    The difference between the morning and bedtime dosing groups in nighttime systolic BP reduction in mmHg measured by the ambulatory BP monitoring after the treatment for 24 weeks

    Time frame: 24 weeks

Secondary outcomes

  1. Daytime systolic BP reduction in mmHg, 24-Hour systolic BP reduction in mmHg, Home systolic BP reduction in mmHg

    The difference between the morning and bedtime dosing groups in the daytime and 24-hour systolic BPs reduction in mmHg measured by the ambulatory BP monitoring and home systolic BP reduction in mmHg after treatment for 24 weeks

    Time frame: 24 weeks

  2. Brachial-ankle pulse wave velocity reduction in cm per second

    The difference between the morning and bedtime dosing groups in reduction of brachial-ankle pulse wave velocity after treatment for 12 and 24 weeks

    Time frame: 12 and 24 weeks

  3. Ambulatory night-to-day BP ratio change in percent; proportions of non-dippers in percent, morning systolic blood pressure in mmHg,

    The difference between the morning and bedtime dosing groups in change of Ambulatory night-to-day BP ratio change in percent; proportions of non-dippers in percent, and morning systolic blood pressure in mmHg after treatment for 8 and 24 weeks.

    Time frame: 8 weeks and 24 weeks

  4. Urinary albumine-to-creatinine ratio change in mg/mmol

    The difference between the morning and bedtime dosing groups in change of microalbumine-to-creatinine ratio in random urine samples after treatment for 12 weeks and 24 weeks

    Time frame: 12 weeks and 24 weeks

  5. change in prevalence of left ventricular hypertrophy defined based on electrocardiogram

    The difference between the morning and bedtime dosing groups in the change in prevalence (percentage) of left ventricular hypertrophy defined based on Cornell product and Sokolow-Lyon index in electrocardiogram after treatment for 12 weeks and 24 weeks

    Time frame: 12 weeks and 24 weeks

  6. change in prevalence of left ventricular hypertrophy defined based on echocardiography

    prevalence (percentage) of left ventricular hypertrophy defined based on left ventricular mass index assessed by echocardiography after treatment for 24 weeks

    Time frame: 24 weeks

  7. Serum uric acid in umol/L

    The difference between the morning and bedtime dosing groups in serum uric acid in umol/L after treatment for 24 weeks

    Time frame: 24 weeks

  8. The difference in daytime systolic and diastolic BPs between the ambulatory and home BP monitoring at baseline and after treatment for 24 weeks

    The difference in daytime systolic and diastolic BPs between the ambulatory and home BP monitoring at baseline and after treatment for 24 weeks

    Time frame: 24 weeks

  9. The difference in nighttime systolic and diastolic BPs between the ambulatory and home BP monitoring at baseline and after treatment for 24 weeks

    The difference in nighttime systolic and diastolic BPs between the ambulatory and home BP monitoring at baseline and after treatment for 24 weeks

    Time frame: 24 weeks

06

Study locations

1 of 1 sites recruiting
  • Ruijin Hospital
    Shanghai, Shanghai 200025, China
    • Yan Li, Professor · Contact · liyanshcn@163.com · 021-64370045
    • Yan Li, Professor · Contact
    Recruiting
07

Registry details

Key details

Study ID
NCT05089448
Lead sponsor
Yan Li
Responsible party
Yan Li (Professor of Cardiovascular Medicine, Shanghai Institute of Hypertension) — Sponsor-investigator
First posted
Oct 22, 2021
Start date
Jan 28, 2021
Primary completion
Jun 30, 2026 (estimated)
Completion
Sep 30, 2026 (estimated)
Last update
Jan 6, 2025

Study contacts

Li Yan, Professor
Contact
liyanshcn@163.com
021-64370045 ext. 663228

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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