Clinical trial NCT05089448: 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
Overall status: RECRUITING
Phase: PHASE4
Conditions: Hypertension
Blood Pressure
Drug Use
Lead sponsor: Shanghai Institute of Hypertension
Sponsor class: OTHER
First posted: 2021-10-22
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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:

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.

Primary outcomes:
measure: Nighttime systolic BP reduction in mmHg
timeFrame: 24 weeks
Secondary outcomes:
measure: Daytime systolic BP reduction in mmHg, 24-Hour systolic BP reduction in mmHg, Home systolic BP reduction in mmHg
timeFrame: 24 weeks
measure: Brachial-ankle pulse wave velocity reduction in cm per second
timeFrame: 12 and 24 weeks
measure: Ambulatory night-to-day BP ratio change in percent; proportions of non-dippers in percent, morning systolic blood pressure in mmHg,
timeFrame: 8 weeks and 24 weeks
measure: Urinary albumine-to-creatinine ratio change in mg/mmol
timeFrame: 12 weeks and 24 weeks
measure: change in prevalence of left ventricular hypertrophy defined based on electrocardiogram
timeFrame: 12 weeks and 24 weeks
measure: change in prevalence of left ventricular hypertrophy defined based on echocardiography
timeFrame: 24 weeks
measure: Serum uric acid in umol/L
timeFrame: 24 weeks
measure: The difference in daytime systolic and diastolic BPs between the ambulatory and home BP monitoring at baseline and after treatment for 24 weeks
timeFrame: 24 weeks
measure: The difference in nighttime systolic and diastolic BPs between the ambulatory and home BP monitoring at baseline and after treatment for 24 weeks
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital
state: Shanghai
Study officials:
References: