The Effect of Nitrendipine/Atenolol Combination on Blood Pressure Variability.

Study Overview
=================
Brief Summary
-----------------
Study name: The Effect of Nitrendipine/Atenolol Combination on Blood Pressure Variability. Medicine: Nitrendipine/Atenolol; Nitrendipine; Atenolol. Rationale: Blood pressure variability correlates with cardiovascular events and target-organ damage in hypertensive patients. Nitrendipine/Atenolol has obvious advantages in reducing blood pressure variability in hypertensive rats, but the effect of this combination on hypertensive patients is still unknown. Objective: To evaluate the effect of nitrendipine/atenolol on blood pressure variability of patients with Grade 1 hypertension compared with nitrendipine or atenolol monotherapy. Study design: This study is a cross-over, randomized, controlled clinical trial with two equally sized treatment groups: Nitrendipine/Atenolol (5mg/10mg); Nitrendipine (10mg) or atenolol (25mg). Study population: Men and Women aged 30-65 years (n=32) meeting the inclusion/exclusion criteria. Randomization and cross-over design: Eligible patients will be randomly divided into two groups. Half of patients will take nitrendipine/atenolol (5/10mg) once daily for 6 weeks first, and then evenly turn into nitrendipine (10mg) or atenolol (25mg) once daily for 6 weeks. Another half of patients will evenly take nitrendipine (10mg) or atenolol (25mg) first, and turn into nitrendipine/atenolol (5/10mg) next. Follow up: 14 weeks. Sample size: a total of 32 patients should be enrolled. Timeline: After obtaining the approval of Ethics Committee of Ruijin Hospital in April 2021, recruitment will start. Patients enrollment and follow-up will be performed between June 2021 to June 2022.

Detailed Description
-----------------
Study name: The effect of Nitrendipine/Atenolol combination on blood pressure variability of patients with Grade 1 hypertension compared with nitrendipine or atenolol monotherapy. Medicine: Nitrendipine/Atenolol (5/10mg tablet); Nitrendipine (10mg tablet); Atenolol (25mg tablet) Rationale: Blood pressure variability correlates with cardiovascular events and target-organ damage in hypertensive patients. Nitrendipine/Atenolol has obvious advantages in reducing blood pressure variability in hypertensive rats, but the effect of this combination on hypertensive patients is still unknown. Objective: To evaluate the effect of nitrendipine/atenolol on blood pressure variability of patients with Grade 1 hypertension compared with nitrendipine or atenolol monotherapy. Study design: This study is a cross-over, randomized, controlled clinical trial with two equally sized treatment groups: Nitrendipine/Atenolol (5mg/10mg); Nitrendipine (10mg) or atenolol (25mg). Study population: Eligible patients (n=32) should be men or women aged 30-65 years. Untreated patients diagnosed as essential hypertension, whose daytime systolic blood pressure ≥ 135mmHg and/or daytime diastolic blood pressure ≥ 85mmHg, and standard deviation (SD)≥13mmHg will be recruited. Randomization and cross-over design: Eligible patients will be randomly divided into two groups. Half of patients will take nitrendipine/atenolol (5/10mg) once daily for 6 weeks first, and then evenly turn into nitrendipine (10mg) or atenolol (25mg) once daily for 6 weeks. Another half of patients will evenly take nitrendipine (10mg) or atenolol (25mg) first, and turn into nitrendipine/atenolol (5/10mg) next. Follow up: 14 weeks. 1 week for screening period, 6 weeks for the first period of treatment, 1 week for wash-out period, and 6 weeks for the second period of treatment. Sample size: a total of 32 patients should be enrolled. Timeline: After obtaining the approval of Ethics Committee of Ruijin Hospital in April 2021, recruitment will start. Patients enrollment and follow-up will be performed between June 2021 to June 2022. Organization: The Centre for Epidemiological Studies and Clinical Trials, Ruijin Hospital, Shanghai, China.

Official Title
-----------------
The Effect of Nitrendipine/Atenolol Combination on Blood Pressure Variability of Patients With Grade 1 Hypertension Compared With Nitrendipine or Atenolol Monotherapy.

Conditions
-----------------
Hypertension

Intervention / Treatment
-----------------
* Drug: Nitrendipine/Atenolol
* Drug: Nitrendipine
* Drug: Atenolol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men or Women. Aged 30-65 years. Ambulatory systolic blood pressure ≥ 135 mmHg and/or diastolic blood pressure ≥ 85 mmHg. Ambulatory daytime systolic blood pressure standard deviation (SD)≥13mmHg. Never took antihypertensive drugs. Signed the written consent. Exclusion Criteria: Under antihypertensive treatments. Clinic systolic blood pressure ≥ 160mmHg and/or diastolic blood pressure ≥ 100mmHg. Contraindications to the treatment of drugs, including hypersensitivity reaction, bradycardia, asthma, etc. Any cardiovascular disease except hypertension. Suspected or confirmed secondary hypertension. Poor compliance.

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Half of patients will take nitrendipine/atenolol (5/10mg) once daily for 6 weeks first, and then evenly turn into nitrendipine (10mg) or atenolol (25mg) once daily for 6 weeks. Another half of patients will evenly take nitrendipine (10mg) or atenolol (25mg) first, and turn into nitrendipine/atenolol (5/10mg) next.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1<br>One pill of nitrendipine/atenolol combination (5/10mg) once daily for 6 weeks first, and followed by monotherapy for another 6 weeks, when patients will evenly assigned to one pill of nitrendipine (10mg) or one pill of atenolol (25mg) once daily. | Drug: Nitrendipine/Atenolol<br>* Nitrendipine/Atenolol 5mg/10mg single-pill combination, oral tablet, one pill daily.<br>* Other names: Nitrendipine and Atenolol Tablets;Drug: Nitrendipine<br>* Nitrendipine 5mg, oral tablet, one pill daily.<br>* Other names: Nitrendipine Tablets;Drug: Atenolol<br>* Atenolol 25mg, oral tablet, one pill daily.<br>* Other names: Atenolol Tablets;|
| Experimental: Sequence 2<br>Monotherapy for 6 weeks first, when patients will evenly assigned to one pill of nitrendipine (10mg) or one pill of atenolol (25mg) once daily, followed by one pill of nitrendipine/atenolol combination (5/10mg) once daily for another 6 weeks. | Drug: Nitrendipine/Atenolol<br>* Nitrendipine/Atenolol 5mg/10mg single-pill combination, oral tablet, one pill daily.<br>* Other names: Nitrendipine and Atenolol Tablets;Drug: Nitrendipine<br>* Nitrendipine 5mg, oral tablet, one pill daily.<br>* Other names: Nitrendipine Tablets;Drug: Atenolol<br>* Atenolol 25mg, oral tablet, one pill daily.<br>* Other names: Atenolol Tablets;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ambulatory systolic blood pressure variability 1 | Including the average real variability (ARV), the coefficient of variation (CV),and the standard deviation (SD). | The first 6 weeks of treatment. | 
| Ambulatory systolic blood pressure variability 2 | Including the average real variability (ARV), the coefficient of variation (CV),and the standard deviation (SD). | The second 6 weeks of cross-over treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ambulatory diastolic blood pressure variability 1 | Including the average real variability (ARV), the coefficient of variation (CV),and the standard deviation (SD). | The first 6 weeks of treatment. | 
| Ambulatory diastolic blood pressure variability 2 | Including the average real variability (ARV), the coefficient of variation (CV),and the standard deviation (SD). | The second 6 weeks of cross-over treatment. | 
| Ambulatory blood pressure 1 | Including ambulatory blood pressure over 24 hours, daytime and nighttime. | The first 6 weeks of treatment. | 
| Ambulatory blood pressure 2 | Including ambulatory blood pressure over 24 hours, daytime and nighttime. | The second 6 weeks of cross-over treatment. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
nitrendipine, blood pressure variability, atenolol