Last updated on September 2018

ACEI/CCB Versus ACEI/DIU Combination Antihypertensive Therapy in Chinese Hypertensive Patients (ACvAD)


Brief description of study

  1. Study name: ACEI/CCB versus ACEI/DIU combination antihypertensive therapy in Chinese hypertensive patients (ACvAD)
  2. Medicine: Benazepril 10 mg / amlodipine besylate 5 mg fixed-dose combination, benazepril 10 mg / hydrochlorothiazide 12.5 mg fixed-dose combination.
  3. Rationale:Most hypertension guidelines, including the Chinese guidelines for hypertension, recommend the combination of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) and calcium antagonists (CCB) or thiazide diuretics (DIU). However, whether the two combination treatments have similar antihypertensive effects in Chinese hypertensive patients still lack clinical trial evidence, especially when randomized controlled trials use dynamic or family blood pressure monitoring as the main evaluation method.
  4. Objective: The main goal of this study is to evaluate the decrease range of 24-hour dynamic systolic blood pressure in the ACEI/CCB group compared with the ACEI/DIU group after 6 months antihypertensive treatment.
  5. Study design: This study is a multicenter, randomized controlled clinical trial with two arms (sample size is the same): ACEI/CCB and ACEI/DIU arm.
  6. Study population: Men and Women aged over 18 (n=580) meet the inclusion/exclusion criteria.
  7. Randomization and treatment: Eligible patients should be monitored 24-hour blood pressure before enrollment. Then randomly divided into two groups according to the center and whether receive antihypertensive treatment, taking benazepril 10 mg/amlodipine besylate 5mg fixed-dose combination (1 tablet once a day) or benazepril 10mg / hydrochlorothiazide 12.5mg fixed-dose combination (1 tablet once a day).
  8. Follow up: All eligible patients sign an informed consent before entering the study. The follow-period is 6 months.
  9. Sample size estimation: The number of required subjects for the study is 580.
  10. Timeline: Ethical review: November 2017; Enrollment: January-February 2018; End of follow-up: August 2018.
  11. Organization: The Centre for Epidemiological Studies and Clinical Trials, Ruijin Hospital, Shanghai, China.

Detailed Study Description

  1. Study name: ACEI/CCB versus ACEI/DIU combination antihypertensive therapy in Chinese hypertensive patients (ACvAD)
  2. Medicine: Benazepril 10 mg / amlodipine besylate 5 mg fixed-dose combination, benazepril 10 mg / hydrochlorothiazide 12.5 mg fixed-dose combination.
  3. Rationale: A meta-analysis of 42 studies showed that the combination of two antihypertensive drugs is better than a single drug to control blood pressure [1]. Most patients with grade 2 or higher hypertension need two or more antihypertensive drugs to control blood pressure. Combined antihypertensive therapy can not only control blood pressure and improve patient compliance, but also reduce adverse drug reactions. For patients who have not received antihypertensive therapy and have high blood pressure levels, the guidelines recommend that combination therapy can be used in the initial treatment. The fixed-dose combination can not only obtain the curative effect, but also can improve patient compliance by reducing the number of tablets [2]. Most hypertension guidelines, including the Chinese guidelines for hypertension, recommend the combination of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) and calcium antagonists (CCB) or thiazide diuretics (DIU). However, whether the two combination treatments have similar antihypertensive effects in Chinese hypertensive patients still lack clinical trial evidence, especially when randomized controlled trials use dynamic or family blood pressure monitoring as the main evaluation method. This study will conduct a randomized controlled clinical trial in a large sample of Chinese hypertensive patients, by measuring office blood pressure, monitoring 24-hour ambulatory blood pressure and home blood pressure to compare the impact of benazepril 10 mg / amlodipine besylate 5 mg fixed-dose combination and benazepril 10 mg / hydrochlorothiazide 12.5 mg fixed-dose combination on office, 24-hour, morning, daytime and nocturnal blood pressure.
  4. Objective: The main goal of this study is to evaluate the decrease range of 24-hour dynamic systolic blood pressure in the ACEI/CCB group compared with the ACEI/DIU group after 6 months antihypertensive treatment. The secondary goal is to compare decrease range of 24-hour dynamic diastolic blood pressure, daytime systolic and diastolic blood pressure, night systolic and diastolic blood pressure, family systolic and diastolic blood pressure, office systolic and diastolic blood pressure at 6-month follow-up.
  5. Study design: This study is a multicenter, randomized controlled clinical trial with two arms (sample size is the same): ACEI/CCB and ACEI/DIU arm.
  6. Study population: Screening of newly diagnosed grade 2 hypertensive patients over the age of 18 or patients who cannot control blood pressure by monotherapy. Patients who never taking antihypertensive drugs or stop taking antihypertensive drugs for more than 2 weeks, or receiving single-drug antihypertensive therapy, systolic blood pressure 140-179mmHg, or diastolic blood pressure 90-109mmHg, entering 4weeks observation period before enrollment. During the observation period, all patients take benazepril 10 mg daily, and office follow-up at 2 weeks and 4 weeks. If patients can take benazepril for 4 weeks continually, no adverse reaction, the mean systolic blood pressure of 6 office blood pressure readings is between 140 and 179mmHg, diastolic blood pressure 90-109mmHg in 2 office follow-ups, then can start group randomizing, using benazepril and switching to study medication. Regardless of whether the office blood pressure is in accordance with the enrollment conditions, monitoring family blood pressure for one week before randomizing, the blood pressure is measured twice every morning and night by an electronic sphygmomanometer. Exclusion criteria include: suspected or confirmed secondary hypertension; history of coronary heart disease, myocardial infarction, heart failure, stroke or dementia; other drugs that may affect blood pressure; liver function (ALT, AST, TBL) results Twice the upper limit, serum creatinine 1.5mg/dl (133mol/L), urine routine protein (+) or higher; blood potassium>5.5mmol/L or <3.5mmol/L; history of gout or male blood uric acid 420mol/L, female 360mol/L; elderly nursing home patients; or patients who are participating in other clinical trials.
  7. Randomization and treatment: Eligible patients should be monitored 24-hour blood pressure before enrollment. Then randomly divided into two groups according to the center and whether receive antihypertensive treatment, taking benazepril 10 mg/amlodipine besylate 5mg fixed-dose combination, 1 tablet once a day, or benazepril 10mg / hydrochlorothiazide 12.5mg fixed-dose combination, 1 tablet once a day. If the systolic/diastolic blood pressure is 140/90 mmHg during follow-up, the dose can be increased to 2 tablets once a day. If the systolic /diastolic blood pressure continues 140/90mmHg, bisoprolol 5mg (1 tablet once a day) or doxazosin controlled-release tablets 4mg (1 tablet once a day) or spironolactone 20mg (1 tablet once a day) can be added further.
  8. Follow up: All eligible patients sign an informed consent form before entering the study. The Omron electronic sphygmomanometer is used to measure the sitting blood pressure in the clinic, and the medical history will be asked. Clinical examinations include dynamic blood pressure monitoring, home blood pressure monitoring, electrocardiogram, blood and urine routine, and biochemical tests. Patients will be followed up every month, measuring sitting blood pressure and asking about adverse events etc; using an automatic transmission electronic sphygmomanometer to monitor one-week home blood pressure before each follow-up; monitoring dynamic blood pressure, home blood pressure, electrocardiogram, blood and urine routine for 6 months after randomization.
  9. Sample size estimation: The primary outcome is the 24-hour dynamic systolic blood pressure reduction at 6-month follow-up compared with baseline in two groups. Assume that the difference between groups is 2.5mmHg, the standard deviation is 10mmHg, =0.05, and the power is 80%. Each group needs 252 patients, if there is an additional 15% increase in cases, then each group should select at least 290 eligible patients and the total is 580 patients. The data will be analyzed by SAS software, and the t-test is used to compare the two groups.
  10. Timeline: Ethical review: November 2017; Enrollment: January-February 2018; End of follow-up: August 2018. At the same time, starting statistical analysis and publishing research results at appropriate domestic or international conferences. The main results will be published in international medical journals.
  11. Organization: The Centre for Epidemiological Studies and Clinical Trials, Ruijin Hospital, Shanghai, China.

Clinical Study Identifier: NCT03682692

Find a site near you

Start Over