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)

Overview

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.

Interventions

• Drug Alisartan, Amlodipine besylate
  Drugs will be taken once daily at 6:00-10:00.
• Drug Alisartan, Amlodipine besylate
  Drugs will be taken once daily at 20:00-24:00.

Primary outcome measures

• Nighttime systolic BP reduction in mmHg [Time frame: 24 weeks]

Secondary outcome measures (9)

• Daytime systolic BP reduction in mmHg, 24-Hour systolic BP reduction in mmHg, Home systolic BP reduction in mmHg [Time frame: 24 weeks]
• Brachial-ankle pulse wave velocity reduction in cm per second [Time frame: 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, [Time frame: 8 weeks and 24 weeks]
• Urinary albumine-to-creatinine ratio change in mg/mmol [Time frame: 12 weeks and 24 weeks]
• change in prevalence of left ventricular hypertrophy defined based on electrocardiogram [Time frame: 12 weeks and 24 weeks]
• change in prevalence of left ventricular hypertrophy defined based on echocardiography [Time frame: 24 weeks]
• Serum uric acid in umol/L [Time frame: 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]
• 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]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Ruijin Hospital — Shanghai

Identifiers

NCT: NCT05089448 · Dosing-Time Trial20210118

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗