Back to resultsMorning Versus Bedtime Dosing of Antihypertensive Medication
Primary Purpose
Hypertension, Blood Pressure, Drug Use
Status
Unknown status
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Alisartan, Amlodipine besylate
Alisartan, Amlodipine besylate
Sponsored by
About this trial
This is an interventional treatment trial for Hypertension
Eligibility Criteria
Inclusion Criteria:
- Male or female patients aged 18-70 years old;
- Never treated for hypertension or stopped using antihypertensive drugs for at least 2 weeks;
- In the two screenings,the clinical systolic BP should be in the range of 140-159 mmHg, the diastolic BP < 100 mmHg;
- The average 24-hour systolic BP ≥130mmHg, daytime systolic BP ≥ 135 mmHg, and nighttime systolic BP ≥ 120 mmHg;
- The average of bilateral brachial-ankle pulse wave velocity ≥14m/s;
- Be willing to participate in the trial, sign the informed consent form, and be able to visit doctors by himself or herself.
Exclusion Criteria:
- Secondary hypertension;
- Concomitant obstructive sleep apnea (STOP-BANG score ≥ 5), insomnia, Parkinson's syndrome, or nocturnal polyuria and other diseases that affect nighttime BP;
- Need to work at night;
- Ambulatory BP monitoring was invalid (<70% valid readings, or <20 daytime readings or <7 nighttime readings);
- Concomitant diseases that need taking medications influencing BP;
- Coronary heart disease, myocardial infarction or stroke within recent 6 months;
- Atrial fibrillation or frequent arrhythmia;
- 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;
- Pregnant or lactating women;
- Contraindications of angiotensin II receptor blocker or calcium channel blocker;
- 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.
Sites / Locations
- Ruijin HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
The morning dosing group
The bedtime dosing group
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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
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.
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
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
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
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
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05089448
Brief Title
Morning Versus Bedtime Dosing of Antihypertensive Medication
Official Title
Morning Versus Bedtime Dosing of Antihypertensive Medication in Grade 1 Day-night Hypertension: a Multicenter Randomized Controlled Trial (Dosing-Time Trial)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Unknown status
Study Start Date
January 28, 2021 (Actual)
Primary Completion Date
January 30, 2023 (Anticipated)
Study Completion Date
January 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Yan Li
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension, Blood Pressure, Drug Use
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
300 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
The morning dosing group
Arm Type
Active Comparator
Arm Description
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.
Arm Title
The bedtime dosing group
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Alisartan, Amlodipine besylate
Intervention Description
Drugs will be taken once daily at 6:00-10:00.
Intervention Type
Drug
Intervention Name(s)
Alisartan, Amlodipine besylate
Intervention Description
Drugs will be taken once daily at 20:00-24:00.
Primary Outcome Measure Information:
Title
Nighttime systolic BP reduction in mmHg
Description
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 Outcome Measure Information:
Title
Daytime systolic BP reduction in mmHg, 24-Hour systolic BP reduction in mmHg, Home systolic BP reduction in mmHg
Description
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
Title
Brachial-ankle pulse wave velocity reduction in cm per second
Description
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
Title
Ambulatory night-to-day BP ratio change in percent; proportions of non-dippers in percent, morning systolic blood pressure in mmHg,
Description
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
Title
Urinary albumine-to-creatinine ratio change in mg/mmol
Description
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
Title
change in prevalence of left ventricular hypertrophy defined based on electrocardiogram
Description
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
Title
change in prevalence of left ventricular hypertrophy defined based on echocardiography
Description
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
Title
Serum uric acid in umol/L
Description
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
Title
The difference in daytime systolic and diastolic BPs between the ambulatory and home BP monitoring at baseline and after treatment for 24 weeks
Description
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
Title
The difference in nighttime systolic and diastolic BPs between the ambulatory and home BP monitoring at baseline and after treatment for 24 weeks
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female patients aged 18-70 years old;
Never treated for hypertension or stopped using antihypertensive drugs for at least 2 weeks;
In the two screenings,the clinical systolic BP should be in the range of 140-159 mmHg, the diastolic BP < 100 mmHg;
The average 24-hour systolic BP ≥130mmHg, daytime systolic BP ≥ 135 mmHg, and nighttime systolic BP ≥ 120 mmHg;
The average of bilateral brachial-ankle pulse wave velocity ≥14m/s;
Be willing to participate in the trial, sign the informed consent form, and be able to visit doctors by himself or herself.
Exclusion Criteria:
Secondary hypertension;
Concomitant obstructive sleep apnea (STOP-BANG score ≥ 5), insomnia, Parkinson's syndrome, or nocturnal polyuria and other diseases that affect nighttime BP;
Need to work at night;
Ambulatory BP monitoring was invalid (<70% valid readings, or <20 daytime readings or <7 nighttime readings);
Concomitant diseases that need taking medications influencing BP;
Coronary heart disease, myocardial infarction or stroke within recent 6 months;
Atrial fibrillation or frequent arrhythmia;
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;
Pregnant or lactating women;
Contraindications of angiotensin II receptor blocker or calcium channel blocker;
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Li Yan, Professor
Phone
021-64370045
Ext
663228
Email
liyanshcn@163.com
Facility Information:
Facility Name
Ruijin Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200025
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yan Li, Professor
Phone
021-64370045
Ext
663228
Email
liyanshcn@163.com
First Name & Middle Initial & Last Name & Degree
Yan Li, Professor
12. IPD Sharing Statement
Learn more about this trial
Morning Versus Bedtime Dosing of Antihypertensive Medication
We'll reach out to this number within 24 hrs