This study aims to compare the antihypertensive effect of initial treatment with a single capsule containing quadruple combination of half-dose of blood pressure medicines or standard dose dual combination in patients with hypertension.

This is a single-center, randomized, double-blind, crossover trial, planning to enroll 90 patients with grade 1 and 2 hypertension in the Third Xiangya Hospital of Central South University. The participants will be divided into two groups randomly and treated with half-dose quadruple antihypertensive therapy (irbesartan 75mg+ metoprolol 23.75mg+ amlodipine 2.5mg+ indapamide 1.25mg) or with full-dose dual antihypertensive therapy (irbesartan 150mg+ amlodipine 5mg) for four weeks. After washing out with placebo for two weeks, the participants of the two groups will exchange their medication and be treated for another four weeks. The changes of blood pressure (including 24-hour ambulatory blood pressure, office blood pressure, and home blood pressure) and related adverse effects of the two groups will be compared.

Inclusion Criteria:

• Age ≥18 years, < 80 years old；
• Have never taken antihypertensive medications or have not taken antihypertensive medications in the past 1 month；
• Patients with hypertension (meet the following two parameters to avoid white coat hypertension):a. Office Blood Pressure: systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg measured 3 times on different days;b. ABPM: average blood pressure of 24h ≥130/80 mmHg; Or average blood pressure of daytime ≥135/85 mmHg; Or average blood pressure of night ≥120/70 mmHg;
• Participate voluntarily and sign written informed consent.

Exclusion Criteria:

• Confirmed or highly suspected secondary hypertension, such as primary aldosteronism, Cushing's syndrome, pheochromocytoma or paraganglioma, aortic constriction, renal arterial stenosis, renal hypertension, hyperthyroidism, etc.;
• Severe hypertension: systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg in the consulting room or hypertensive emergency or urgency at the time of visit;
• Differences in blood pressure of both upper limbs ≥20/10mmHg;
• Allergic to irbesartan, metoprolol, amlodipine, indapamide and sulfonamides;
• Cannot swallow tablets;
• Pregnant and lactating women;
• Possible reproductive needs during the trial;
• Uncorrected electrolyte disorder (serum potassium > 5.5mmol/L or < 3.5mmol/L, serum sodium < 135mmol/L);
• Severe organ dysfunction, including impaired renal function (GFR < 60mL /min/1.73m^2), impaired liver function (aspartate aminotransferase or alanine aminotransferase ≥ 3 times the upper limit of normal), NYHF classification class IV for cardiac function;
• Comorbidities lead to inaccurate blood pressure measurement, such as arrhythmia, etc.;
• Comorbidities result in the prohibition or caution of the experimental drugs, such as: aortic stenosis, mitral valve stenosis, hypertrophic obstructive cardiomyopathy, bilateral renal artery stenosis or renal artery stenosis with solitary kidney, gout, hyperuricemia (serum uric acid >420μmol/L in men or 360μmol/L in women), acute coronary syndrome, sick sinus syndrome, degree II-III of atrioventricular block, severe peripheral vascular disease with high risk of gangrene, history or family history of angioedema;
• Comorbidities affect the absorption, distribution, metabolism and excretion of the experimental drugs such as: gastrointestinal resection, gastrointestinal bypass surgery, sympathetic nerve resection or other operations, active inflammatory bowel disease, malignant tumors undergoing or planning to undergo radiotherapy or chemotherapy or targeted therapy, etc.;
• Medications in use or about to be used may lead to the prohibition or caution of experimental drugs: such as ACEI, Aliskiren, lithium agent, etc.;
• Medications in use or about to be used will interfere the results of this study, such as: hormones, Sacubitril valsartan and spironolactone for patients with chronic heart failure, Dapagliflozin and Liraglutide for patients with diabetes, and long-term medication for patients with chronic coronary heart disease, etc.;
• Not appropriate for antihypertensive therapies of this trial evaluated by physician;
• Participating in other clinical research that may affect the conduct of this study.

Study protocol and clinical study report will be shared by publishing way.

When study protocol and clinical study report are accepted to publish, they will be available.

Persons except who make masking plan and conduct medicine coding, are all masked.